TY  - JOUR
AU  - Opačić, Miloš
AU  - Ristic, Aleksandar J
AU  - Sokic, Dragoslav
AU  - Baščarević, Vladimir
AU  - Raicević, Savo
AU  - Savić, Slobodan
AU  - Zorović, Maja
AU  - Zivin, Marko
AU  - Selih, Vid Simon
AU  - Spasojević, Ivan
AU  - Savić, Danijela Z
PY  - 2021
UR  - http://rimsi.imsi.bg.ac.rs/handle/123456789/1515
AB  - Introduction Disruption of copper homeostasis and dysfunction of mitochondria have been documented in sclerotic hippocampi (HS) of patients with mesial temporal lobe epilepsy (mTLE). However, a potential link between these pathological changes has not been tackled so far. Herein, we analyzed regional distribution of neuron somata density, copper concentration, and the activity of cytochrome c oxidase (CCO), a component of mitochondrial electron transport chain and copper-containing metalloprotein, in HS. Methods Histochemical staining and laser ablation inductively coupled plasma mass spectrometry were carried out to construct comparable maps of these parameters in coronal sections of hippocampi of 3 mTLE-HS patients and 3 control subjects. Results Copper levels were decreased in all regions of HS with pyramidal neuron somata. CCO activity was significantly reduced in stratum pyramidale (PY) 1 and cornu Ammonis field 4, the two regions with significant reduction in neuron somata density. CCO activity was also lower in layers that contain apical dendrites of pyramidal neurons and mossy fibers. It appears that copper deficiency in PY2 and PY3 comes before CCO activity reduction and neuronal loss. A strong positive correlation was found between neuron density, Cu concentration, and CCO activity. Conclusions Presented results imply that pathological alterations in Cu and energy metabolism could be involved in the development of HS. A limitation of this study was the relatively small number of patients. However, presented results underline copper deficiency as a component of pathological mechanisms of epilepsy and warrant further investigation of cuproproteins and members of copper transport machinery.
PB  - Wiley, Hoboken
T2  - Brain and Behavior
T1  - Regional distribution of cytochrome c oxidase activity and copper in sclerotic hippocampi of epilepsy patients
IS  - 2
VL  - 11
DO  - 10.1002/brb3.1986
ER  - 

@article{
author = "Opačić, Miloš and Ristic, Aleksandar J and Sokic, Dragoslav and Baščarević, Vladimir and Raicević, Savo and Savić, Slobodan and Zorović, Maja and Zivin, Marko and Selih, Vid Simon and Spasojević, Ivan and Savić, Danijela Z",
year = "2021",
abstract = "Introduction Disruption of copper homeostasis and dysfunction of mitochondria have been documented in sclerotic hippocampi (HS) of patients with mesial temporal lobe epilepsy (mTLE). However, a potential link between these pathological changes has not been tackled so far. Herein, we analyzed regional distribution of neuron somata density, copper concentration, and the activity of cytochrome c oxidase (CCO), a component of mitochondrial electron transport chain and copper-containing metalloprotein, in HS. Methods Histochemical staining and laser ablation inductively coupled plasma mass spectrometry were carried out to construct comparable maps of these parameters in coronal sections of hippocampi of 3 mTLE-HS patients and 3 control subjects. Results Copper levels were decreased in all regions of HS with pyramidal neuron somata. CCO activity was significantly reduced in stratum pyramidale (PY) 1 and cornu Ammonis field 4, the two regions with significant reduction in neuron somata density. CCO activity was also lower in layers that contain apical dendrites of pyramidal neurons and mossy fibers. It appears that copper deficiency in PY2 and PY3 comes before CCO activity reduction and neuronal loss. A strong positive correlation was found between neuron density, Cu concentration, and CCO activity. Conclusions Presented results imply that pathological alterations in Cu and energy metabolism could be involved in the development of HS. A limitation of this study was the relatively small number of patients. However, presented results underline copper deficiency as a component of pathological mechanisms of epilepsy and warrant further investigation of cuproproteins and members of copper transport machinery.",
publisher = "Wiley, Hoboken",
journal = "Brain and Behavior",
title = "Regional distribution of cytochrome c oxidase activity and copper in sclerotic hippocampi of epilepsy patients",
number = "2",
volume = "11",
doi = "10.1002/brb3.1986"
}

Opačić, M., Ristic, A. J., Sokic, D., Baščarević, V., Raicević, S., Savić, S., Zorović, M., Zivin, M., Selih, V. S., Spasojević, I.,& Savić, D. Z.. (2021). Regional distribution of cytochrome c oxidase activity and copper in sclerotic hippocampi of epilepsy patients. in Brain and Behavior
Wiley, Hoboken., 11(2).
https://doi.org/10.1002/brb3.1986

Opačić M, Ristic AJ, Sokic D, Baščarević V, Raicević S, Savić S, Zorović M, Zivin M, Selih VS, Spasojević I, Savić DZ. Regional distribution of cytochrome c oxidase activity and copper in sclerotic hippocampi of epilepsy patients. in Brain and Behavior. 2021;11(2).
doi:10.1002/brb3.1986 .

Opačić, Miloš, Ristic, Aleksandar J, Sokic, Dragoslav, Baščarević, Vladimir, Raicević, Savo, Savić, Slobodan, Zorović, Maja, Zivin, Marko, Selih, Vid Simon, Spasojević, Ivan, Savić, Danijela Z, "Regional distribution of cytochrome c oxidase activity and copper in sclerotic hippocampi of epilepsy patients" in Brain and Behavior, 11, no. 2 (2021),
https://doi.org/10.1002/brb3.1986 . .

TY  - JOUR
AU  - Korać Jačić, Jelena
AU  - Nikolić, Ljiljana M.
AU  - Stanković, Dalibor M.
AU  - Opačić, Miloš
AU  - Dimitrijević, Milena
AU  - Savić, Danijela Z
AU  - Grguric-Sipka, Sanja
AU  - Spasojević, Ivan
AU  - Bogdanović Pristov, Jelena
PY  - 2020
UR  - http://rimsi.imsi.bg.ac.rs/handle/123456789/1344
AB  - Upon release in response to stress, epinephrine (Epi) may interact with labile iron pool in human plasma with potentially important (patho)physiological consequences. We have shown that Epi and Fe3+ build stable 1:1 high-spin bidentate complex at physiological pH, and that Epi does not undergo degradation in the presence of iron. However, the interactions of Epi with the more soluble Fe2+, and the impact of iron on biological activity of Epi are still not known. Herein we showed that Epi and Fe2+ build colorless complex which is stable under anaerobic conditions. In the presence of O-2, Epi promoted the oxidation of Fe2+ and the formation of Epi-Fe3+ complex. Cyclic voltammetry showed that mid-point potential of Epi-Fe2+ complex is very low (-582 mV vs. standard hydrogen electrode), which explains catalyzed oxidation of Fe2+. Next, we examined the impact of iron binding on biological performance of Epi using patch clamping in cell culture with constitutive expression of adrenergic receptors. Epi alone evoked an increase of outward currents, whereas Epi in the complex with Fe3+ did not. This implies that the binding of Epi to adrenergic receptors and their activation is prevented by the formation of complex with iron. Pro-oxidative activity of Epi-Fe2+ complex may represent a link between chronic stress and cardiovascular problems. On the other hand, labile iron could serve as a modulator of biological activity of ligands. Such interactions may be important in human pathologies that are related to iron overload or deficiency.
PB  - Elsevier Science Inc, New York
T2  - Free Radical Biology and Medicine
T1  - Ferrous iron binding to epinephrine promotes the oxidation of iron and impedes activation of adrenergic receptors
EP  - 127
SP  - 123
VL  - 148
DO  - 10.1016/j.freeradbiomed.2020.01.001
ER  - 

@article{
author = "Korać Jačić, Jelena and Nikolić, Ljiljana M. and Stanković, Dalibor M. and Opačić, Miloš and Dimitrijević, Milena and Savić, Danijela Z and Grguric-Sipka, Sanja and Spasojević, Ivan and Bogdanović Pristov, Jelena",
year = "2020",
abstract = "Upon release in response to stress, epinephrine (Epi) may interact with labile iron pool in human plasma with potentially important (patho)physiological consequences. We have shown that Epi and Fe3+ build stable 1:1 high-spin bidentate complex at physiological pH, and that Epi does not undergo degradation in the presence of iron. However, the interactions of Epi with the more soluble Fe2+, and the impact of iron on biological activity of Epi are still not known. Herein we showed that Epi and Fe2+ build colorless complex which is stable under anaerobic conditions. In the presence of O-2, Epi promoted the oxidation of Fe2+ and the formation of Epi-Fe3+ complex. Cyclic voltammetry showed that mid-point potential of Epi-Fe2+ complex is very low (-582 mV vs. standard hydrogen electrode), which explains catalyzed oxidation of Fe2+. Next, we examined the impact of iron binding on biological performance of Epi using patch clamping in cell culture with constitutive expression of adrenergic receptors. Epi alone evoked an increase of outward currents, whereas Epi in the complex with Fe3+ did not. This implies that the binding of Epi to adrenergic receptors and their activation is prevented by the formation of complex with iron. Pro-oxidative activity of Epi-Fe2+ complex may represent a link between chronic stress and cardiovascular problems. On the other hand, labile iron could serve as a modulator of biological activity of ligands. Such interactions may be important in human pathologies that are related to iron overload or deficiency.",
publisher = "Elsevier Science Inc, New York",
journal = "Free Radical Biology and Medicine",
title = "Ferrous iron binding to epinephrine promotes the oxidation of iron and impedes activation of adrenergic receptors",
pages = "127-123",
volume = "148",
doi = "10.1016/j.freeradbiomed.2020.01.001"
}

Korać Jačić, J., Nikolić, L. M., Stanković, D. M., Opačić, M., Dimitrijević, M., Savić, D. Z., Grguric-Sipka, S., Spasojević, I.,& Bogdanović Pristov, J.. (2020). Ferrous iron binding to epinephrine promotes the oxidation of iron and impedes activation of adrenergic receptors. in Free Radical Biology and Medicine
Elsevier Science Inc, New York., 148, 123-127.
https://doi.org/10.1016/j.freeradbiomed.2020.01.001

Korać Jačić J, Nikolić LM, Stanković DM, Opačić M, Dimitrijević M, Savić DZ, Grguric-Sipka S, Spasojević I, Bogdanović Pristov J. Ferrous iron binding to epinephrine promotes the oxidation of iron and impedes activation of adrenergic receptors. in Free Radical Biology and Medicine. 2020;148:123-127.
doi:10.1016/j.freeradbiomed.2020.01.001 .

Korać Jačić, Jelena, Nikolić, Ljiljana M., Stanković, Dalibor M., Opačić, Miloš, Dimitrijević, Milena, Savić, Danijela Z, Grguric-Sipka, Sanja, Spasojević, Ivan, Bogdanović Pristov, Jelena, "Ferrous iron binding to epinephrine promotes the oxidation of iron and impedes activation of adrenergic receptors" in Free Radical Biology and Medicine, 148 (2020):123-127,
https://doi.org/10.1016/j.freeradbiomed.2020.01.001 . .

TY  - JOUR
AU  - Bijelic, Dunja D.
AU  - Milicević, Katarina
AU  - Lazarević, Milica N.
AU  - Miljković, Đorđe
AU  - Bogdanović Pristov, Jelena
AU  - Savić, Danijela Z
AU  - Petković, Branka
AU  - Andjus, Pavle R.
AU  - Momcilović, Miljana
AU  - Nikolić, Ljiljana M.
PY  - 2020
UR  - http://rimsi.imsi.bg.ac.rs/handle/123456789/1317
AB  - Interaction between autoreactive immune cells and astroglia is an important part of the pathologic processes that fuel neurodegeneration in multiple sclerosis. In this inflammatory disease, immune cells enter into the central nervous system (CNS) and they spread through CNS parenchyma, but the impact of these autoreactive immune cells on the activity pattern of astrocytes has not been defined. By exploiting naive astrocytes in culture and CNS-infiltrated immune cells (CNS IICs) isolated from rat with experimental autoimmune encephalomyelitis (EAE), here we demonstrate previously unrecognized properties of immune cell-astrocyte interaction. We show that CNS IICs but not the peripheral immune cell application, evokes a rapid and vigorous intracellular Ca(2+)increase in astrocytes by promoting glial release of ATP. ATP propagated Ca(2+)elevation through glial purinergic P2X7 receptor activation by the hemichannel-dependent nucleotide release mechanism. Astrocyte Ca(2+)increase is specifically triggered by the autoreactive CD4(+)T-cell application and these two cell types exhibit close spatial interaction in EAE. Therefore, Ca(2+)signals may mediate a rapid astroglial response to the autoreactive immune cells in their local environment. This property of immune cell-astrocyte interaction may be important to consider in studies interrogating CNS autoimmune disease.
PB  - Wiley, Hoboken
T2  - Journal of Neuroscience Research
T1  - Central nervous system-infiltrated immune cells induce calcium increase in astrocytes via astroglial purinergic signaling
EP  - 2332
IS  - 11
SP  - 2317
VL  - 98
DO  - 10.1002/jnr.24699
ER  - 

@article{
author = "Bijelic, Dunja D. and Milicević, Katarina and Lazarević, Milica N. and Miljković, Đorđe and Bogdanović Pristov, Jelena and Savić, Danijela Z and Petković, Branka and Andjus, Pavle R. and Momcilović, Miljana and Nikolić, Ljiljana M.",
year = "2020",
abstract = "Interaction between autoreactive immune cells and astroglia is an important part of the pathologic processes that fuel neurodegeneration in multiple sclerosis. In this inflammatory disease, immune cells enter into the central nervous system (CNS) and they spread through CNS parenchyma, but the impact of these autoreactive immune cells on the activity pattern of astrocytes has not been defined. By exploiting naive astrocytes in culture and CNS-infiltrated immune cells (CNS IICs) isolated from rat with experimental autoimmune encephalomyelitis (EAE), here we demonstrate previously unrecognized properties of immune cell-astrocyte interaction. We show that CNS IICs but not the peripheral immune cell application, evokes a rapid and vigorous intracellular Ca(2+)increase in astrocytes by promoting glial release of ATP. ATP propagated Ca(2+)elevation through glial purinergic P2X7 receptor activation by the hemichannel-dependent nucleotide release mechanism. Astrocyte Ca(2+)increase is specifically triggered by the autoreactive CD4(+)T-cell application and these two cell types exhibit close spatial interaction in EAE. Therefore, Ca(2+)signals may mediate a rapid astroglial response to the autoreactive immune cells in their local environment. This property of immune cell-astrocyte interaction may be important to consider in studies interrogating CNS autoimmune disease.",
publisher = "Wiley, Hoboken",
journal = "Journal of Neuroscience Research",
title = "Central nervous system-infiltrated immune cells induce calcium increase in astrocytes via astroglial purinergic signaling",
pages = "2332-2317",
number = "11",
volume = "98",
doi = "10.1002/jnr.24699"
}

Bijelic, D. D., Milicević, K., Lazarević, M. N., Miljković, Đ., Bogdanović Pristov, J., Savić, D. Z., Petković, B., Andjus, P. R., Momcilović, M.,& Nikolić, L. M.. (2020). Central nervous system-infiltrated immune cells induce calcium increase in astrocytes via astroglial purinergic signaling. in Journal of Neuroscience Research
Wiley, Hoboken., 98(11), 2317-2332.
https://doi.org/10.1002/jnr.24699

Bijelic DD, Milicević K, Lazarević MN, Miljković Đ, Bogdanović Pristov J, Savić DZ, Petković B, Andjus PR, Momcilović M, Nikolić LM. Central nervous system-infiltrated immune cells induce calcium increase in astrocytes via astroglial purinergic signaling. in Journal of Neuroscience Research. 2020;98(11):2317-2332.
doi:10.1002/jnr.24699 .

Bijelic, Dunja D., Milicević, Katarina, Lazarević, Milica N., Miljković, Đorđe, Bogdanović Pristov, Jelena, Savić, Danijela Z, Petković, Branka, Andjus, Pavle R., Momcilović, Miljana, Nikolić, Ljiljana M., "Central nervous system-infiltrated immune cells induce calcium increase in astrocytes via astroglial purinergic signaling" in Journal of Neuroscience Research, 98, no. 11 (2020):2317-2332,
https://doi.org/10.1002/jnr.24699 . .

TY  - CONF
AU  - Opačić, Miloš
AU  - Nestorov, Jelena
AU  - Tasić, Danica
AU  - Bogdanović Pristov, Jelena
AU  - Savić, Danijela Z
AU  - Bascarevic, Vladimir
AU  - Ristic, Aleksandar J
AU  - Sokic, Dragoslav
AU  - Spasojević, Ivan
PY  - 2018
UR  - http://rimsi.imsi.bg.ac.rs/handle/123456789/2810
AB  - Skleroza hipokampusa je najčešći neuropatološki nalaz kod epilepsije temporalnog
režnja. Pored morfoloških promena odlikuju ga i promene nivoa različitih proteina u
ćeliji. Imunoblot je nezamenjiva metoda za određivanje nivoa proteina i podrazumeva
normalizaciju u odnosu na endogenu kontrolu (kontrolu jednakog nanošenja uzorka). Za
tu svrhu se koriste proteini za koje se smatra da imaju stabilnu ekspresiju koja najmanje
varira u ispitivanim uslovima, tretmanima i patofiziološkim stanjima. Ipak u nekim
patofiziološkim stanjima se i ekspresija tradicionalno korišćenih endogenih kontrola
menja,
1
što može dovesti do prikupljanja netačnih podataka i pogrešnog tumačenja
rezultata. Cilj ovog rada je bio da se ispita stabilnost najčešće korišćenih endogenih
kontrola i izabere najstabilnija koja će se koristiti za normalizaciju pri poređenju nivoa
ciljnih proteina hipokampusa obolelih od epilepsije i neurološki intaktnih kontrola.
Imunoblotom su detektovani β-aktin, α-tubulin, TATA-vezujući protein i gliceraldehid3-fosfat dehidrogenaza u tkivnim ekstraktima hipokampusa 9 pacijenata i 7 kontrola, i
NormFinder softverom2
određene unutargrupna i međugrupna varijabilnost. Pokazano je
da nivo strukturnih proteina β-aktina i α-tubulina najmanje varira u ispitivanim uslovima
te se mogu koristiti za poređenje nivoa proteina u sklerotičnim i intaktnim
hipokampusima. Rezultati upućuju da je odabir endogenih kontrola važan preduslov za
dobijanje tačnih i pouzdanih podataka imunoblot metodom.
PB  - Društvo biologa Srbije
C3  - Drugi kongres biologa Srbije Osnovna i primenjena istraživanja metodika nastave
T1  - Odabir endogene kontrole za imunoblot analizu proteina u sklerotičnim hipokampusima pacijenata sa epilepsijom temporalnog režnja
SP  - 164
UR  - https://hdl.handle.net/21.15107/rcub_rimsi_2810
ER  - 

@conference{
author = "Opačić, Miloš and Nestorov, Jelena and Tasić, Danica and Bogdanović Pristov, Jelena and Savić, Danijela Z and Bascarevic, Vladimir and Ristic, Aleksandar J and Sokic, Dragoslav and Spasojević, Ivan",
year = "2018",
abstract = "Skleroza hipokampusa je najčešći neuropatološki nalaz kod epilepsije temporalnog
režnja. Pored morfoloških promena odlikuju ga i promene nivoa različitih proteina u
ćeliji. Imunoblot je nezamenjiva metoda za određivanje nivoa proteina i podrazumeva
normalizaciju u odnosu na endogenu kontrolu (kontrolu jednakog nanošenja uzorka). Za
tu svrhu se koriste proteini za koje se smatra da imaju stabilnu ekspresiju koja najmanje
varira u ispitivanim uslovima, tretmanima i patofiziološkim stanjima. Ipak u nekim
patofiziološkim stanjima se i ekspresija tradicionalno korišćenih endogenih kontrola
menja,
1
što može dovesti do prikupljanja netačnih podataka i pogrešnog tumačenja
rezultata. Cilj ovog rada je bio da se ispita stabilnost najčešće korišćenih endogenih
kontrola i izabere najstabilnija koja će se koristiti za normalizaciju pri poređenju nivoa
ciljnih proteina hipokampusa obolelih od epilepsije i neurološki intaktnih kontrola.
Imunoblotom su detektovani β-aktin, α-tubulin, TATA-vezujući protein i gliceraldehid3-fosfat dehidrogenaza u tkivnim ekstraktima hipokampusa 9 pacijenata i 7 kontrola, i
NormFinder softverom2
određene unutargrupna i međugrupna varijabilnost. Pokazano je
da nivo strukturnih proteina β-aktina i α-tubulina najmanje varira u ispitivanim uslovima
te se mogu koristiti za poređenje nivoa proteina u sklerotičnim i intaktnim
hipokampusima. Rezultati upućuju da je odabir endogenih kontrola važan preduslov za
dobijanje tačnih i pouzdanih podataka imunoblot metodom.",
publisher = "Društvo biologa Srbije",
journal = "Drugi kongres biologa Srbije Osnovna i primenjena istraživanja metodika nastave",
title = "Odabir endogene kontrole za imunoblot analizu proteina u sklerotičnim hipokampusima pacijenata sa epilepsijom temporalnog režnja",
pages = "164",
url = "https://hdl.handle.net/21.15107/rcub_rimsi_2810"
}

Opačić, M., Nestorov, J., Tasić, D., Bogdanović Pristov, J., Savić, D. Z., Bascarevic, V., Ristic, A. J., Sokic, D.,& Spasojević, I.. (2018). Odabir endogene kontrole za imunoblot analizu proteina u sklerotičnim hipokampusima pacijenata sa epilepsijom temporalnog režnja. in Drugi kongres biologa Srbije Osnovna i primenjena istraživanja metodika nastave
Društvo biologa Srbije., 164.
https://hdl.handle.net/21.15107/rcub_rimsi_2810

Opačić M, Nestorov J, Tasić D, Bogdanović Pristov J, Savić DZ, Bascarevic V, Ristic AJ, Sokic D, Spasojević I. Odabir endogene kontrole za imunoblot analizu proteina u sklerotičnim hipokampusima pacijenata sa epilepsijom temporalnog režnja. in Drugi kongres biologa Srbije Osnovna i primenjena istraživanja metodika nastave. 2018;:164.
https://hdl.handle.net/21.15107/rcub_rimsi_2810 .

Opačić, Miloš, Nestorov, Jelena, Tasić, Danica, Bogdanović Pristov, Jelena, Savić, Danijela Z, Bascarevic, Vladimir, Ristic, Aleksandar J, Sokic, Dragoslav, Spasojević, Ivan, "Odabir endogene kontrole za imunoblot analizu proteina u sklerotičnim hipokampusima pacijenata sa epilepsijom temporalnog režnja" in Drugi kongres biologa Srbije Osnovna i primenjena istraživanja metodika nastave (2018):164,
https://hdl.handle.net/21.15107/rcub_rimsi_2810 .

TY  - JOUR
AU  - Opačić, Miloš
AU  - Ristic, Aleksandar J
AU  - Savić, Danijela Z
AU  - Selih, Vid Simon
AU  - Zivin, Marko
AU  - Sokic, Dragoslav
AU  - Raicević, Savo
AU  - Baščarević, Vladimir
AU  - Spasojević, Ivan
PY  - 2017
UR  - http://rimsi.imsi.bg.ac.rs/handle/123456789/1080
AB  - The loss of metal homeostasis has been implicated in the pathophysiology of mesial temporal lobe epilepsy associated with hippocampal sclerosis (mTLE-HS). Here we applied laser ablation inductively coupled plasma mass spectrometry imaging to establish the spatial distribution of Zn, Fe, Cu and Mn in coronal sections of hippocampi of four patients with drug-resistant mTLE-HS who underwent amygdalohippocampectomy. Detailed maps of the metal concentrations in the different morphological areas/layers were built and analyzed. The highest level of Zn (>20 mu g g(-1)) was found in mossy fiber-rich regions -cornu ammonis field 4 (CA4), gyrus dentatus, and CA3. The distribution of Fe appears to reflect the routes of the main intrahippocampal blood vessels. The highest concentrations of Cu (410 mg g(-1)) and Mn (415 mu g g(-1)) were observed in regions/layers with neuron somata - subiculum, CA4, gyrus dentatus, and stratum pyramidale (SPy) in CA1 and CA2. Alveus and other regions with axons and dendrites generally showed lower levels of Zn, Cu, and Mn. The Cu concentration was decreased in the areas of total neuronal loss in SPy in CA1 (9.73 +/- 0.91 mu g g(-1)), compared to the subiculum (13.32 +/- .29 mu g g(-1); p = 0.043). The Cu and Mn concentrations correlated positively with neuron density in the SPy in CA1 (R = 0.629, p o 0.001; and R = 0.391, p = 0.004). These results provide a deeper insight into hippocampal metabolism of metals, and pave the road for identifying the components of the mechanism of epileptogenesis among Cu and Mn transporters and metalloproteins.
PB  - Royal Soc Chemistry, Cambridge
T2  - Metallomics
T1  - Metal maps of sclerotic hippocampi of patients with mesial temporal lobe epilepsy
EP  - 148
IS  - 2
SP  - 141
VL  - 9
DO  - 10.1039/c6mt00293e
ER  - 

@article{
author = "Opačić, Miloš and Ristic, Aleksandar J and Savić, Danijela Z and Selih, Vid Simon and Zivin, Marko and Sokic, Dragoslav and Raicević, Savo and Baščarević, Vladimir and Spasojević, Ivan",
year = "2017",
abstract = "The loss of metal homeostasis has been implicated in the pathophysiology of mesial temporal lobe epilepsy associated with hippocampal sclerosis (mTLE-HS). Here we applied laser ablation inductively coupled plasma mass spectrometry imaging to establish the spatial distribution of Zn, Fe, Cu and Mn in coronal sections of hippocampi of four patients with drug-resistant mTLE-HS who underwent amygdalohippocampectomy. Detailed maps of the metal concentrations in the different morphological areas/layers were built and analyzed. The highest level of Zn (>20 mu g g(-1)) was found in mossy fiber-rich regions -cornu ammonis field 4 (CA4), gyrus dentatus, and CA3. The distribution of Fe appears to reflect the routes of the main intrahippocampal blood vessels. The highest concentrations of Cu (410 mg g(-1)) and Mn (415 mu g g(-1)) were observed in regions/layers with neuron somata - subiculum, CA4, gyrus dentatus, and stratum pyramidale (SPy) in CA1 and CA2. Alveus and other regions with axons and dendrites generally showed lower levels of Zn, Cu, and Mn. The Cu concentration was decreased in the areas of total neuronal loss in SPy in CA1 (9.73 +/- 0.91 mu g g(-1)), compared to the subiculum (13.32 +/- .29 mu g g(-1); p = 0.043). The Cu and Mn concentrations correlated positively with neuron density in the SPy in CA1 (R = 0.629, p o 0.001; and R = 0.391, p = 0.004). These results provide a deeper insight into hippocampal metabolism of metals, and pave the road for identifying the components of the mechanism of epileptogenesis among Cu and Mn transporters and metalloproteins.",
publisher = "Royal Soc Chemistry, Cambridge",
journal = "Metallomics",
title = "Metal maps of sclerotic hippocampi of patients with mesial temporal lobe epilepsy",
pages = "148-141",
number = "2",
volume = "9",
doi = "10.1039/c6mt00293e"
}

Opačić, M., Ristic, A. J., Savić, D. Z., Selih, V. S., Zivin, M., Sokic, D., Raicević, S., Baščarević, V.,& Spasojević, I.. (2017). Metal maps of sclerotic hippocampi of patients with mesial temporal lobe epilepsy. in Metallomics
Royal Soc Chemistry, Cambridge., 9(2), 141-148.
https://doi.org/10.1039/c6mt00293e

Opačić M, Ristic AJ, Savić DZ, Selih VS, Zivin M, Sokic D, Raicević S, Baščarević V, Spasojević I. Metal maps of sclerotic hippocampi of patients with mesial temporal lobe epilepsy. in Metallomics. 2017;9(2):141-148.
doi:10.1039/c6mt00293e .

Opačić, Miloš, Ristic, Aleksandar J, Savić, Danijela Z, Selih, Vid Simon, Zivin, Marko, Sokic, Dragoslav, Raicević, Savo, Baščarević, Vladimir, Spasojević, Ivan, "Metal maps of sclerotic hippocampi of patients with mesial temporal lobe epilepsy" in Metallomics, 9, no. 2 (2017):141-148,
https://doi.org/10.1039/c6mt00293e . .

TY  - JOUR
AU  - Kalauzi, Aleksandar
AU  - Nikolić, Ljiljana M.
AU  - Savić, Danijela Z
AU  - Radotić, Ksenija
PY  - 2015
UR  - http://rimsi.imsi.bg.ac.rs/handle/123456789/897
AB  - The physiological and biochemical factors that lead to cell death have not been recognized completely. To our knowledge, there are no data on the bioelectric parameters that characterize early period of cell death, as well as on the appearance of related membrane current frequencies. We studied early parameters of glutaraldehyde (GA)-induced cell death, by examining the membrane properties of mouse microglia using the whole-cell patch-clamp technique. In addition, we investigated the GA-induced changes in the membrane current frequency, to see if characteristic frequencies would appear in dying cell. For data analysis, we applied a new approach, an improved multiple moving window length analysis and interval weighted spectra averaging (IWSA). We chose GA for its ability to induce almost instantaneous cell death. The 0.6 % GA did not induce changes in the bioelectric membrane properties of microglia. However, the 3 % GA caused significant decrease of membrane capacitance and resistance accompanied by the prominent increase in the membrane currents and nearly ohmic current response of microglial cells. These data indicate that 3 % GA caused complete loss of the membrane function consequently inducing instantaneous cell death. The membrane function loss was characterized by appearance of the 1.26-4.62 Hz frequency peak in the IWSA spectra, while no significant increase of amplitudes could be observed for cells treated with 0.6 % GA. To our knowledge, this is the first record of a frequency associated with complete loss of the membrane function and thus can be considered as an early indicator of cell death.
PB  - Springer, New York
T2  - Journal of Membrane Biology
T1  - Cell Death Parameters as Revealed by Whole-Cell Patch-Clamp and Interval Weighted Spectra Averaging: Changes in Membrane Properties and Current Frequency of Cultured Mouse Microglial Cells Induced by Glutaraldehyde
EP  - 123
IS  - 1
SP  - 117
VL  - 248
DO  - 10.1007/s00232-014-9748-7
ER  - 

@article{
author = "Kalauzi, Aleksandar and Nikolić, Ljiljana M. and Savić, Danijela Z and Radotić, Ksenija",
year = "2015",
abstract = "The physiological and biochemical factors that lead to cell death have not been recognized completely. To our knowledge, there are no data on the bioelectric parameters that characterize early period of cell death, as well as on the appearance of related membrane current frequencies. We studied early parameters of glutaraldehyde (GA)-induced cell death, by examining the membrane properties of mouse microglia using the whole-cell patch-clamp technique. In addition, we investigated the GA-induced changes in the membrane current frequency, to see if characteristic frequencies would appear in dying cell. For data analysis, we applied a new approach, an improved multiple moving window length analysis and interval weighted spectra averaging (IWSA). We chose GA for its ability to induce almost instantaneous cell death. The 0.6 % GA did not induce changes in the bioelectric membrane properties of microglia. However, the 3 % GA caused significant decrease of membrane capacitance and resistance accompanied by the prominent increase in the membrane currents and nearly ohmic current response of microglial cells. These data indicate that 3 % GA caused complete loss of the membrane function consequently inducing instantaneous cell death. The membrane function loss was characterized by appearance of the 1.26-4.62 Hz frequency peak in the IWSA spectra, while no significant increase of amplitudes could be observed for cells treated with 0.6 % GA. To our knowledge, this is the first record of a frequency associated with complete loss of the membrane function and thus can be considered as an early indicator of cell death.",
publisher = "Springer, New York",
journal = "Journal of Membrane Biology",
title = "Cell Death Parameters as Revealed by Whole-Cell Patch-Clamp and Interval Weighted Spectra Averaging: Changes in Membrane Properties and Current Frequency of Cultured Mouse Microglial Cells Induced by Glutaraldehyde",
pages = "123-117",
number = "1",
volume = "248",
doi = "10.1007/s00232-014-9748-7"
}

Kalauzi, A., Nikolić, L. M., Savić, D. Z.,& Radotić, K.. (2015). Cell Death Parameters as Revealed by Whole-Cell Patch-Clamp and Interval Weighted Spectra Averaging: Changes in Membrane Properties and Current Frequency of Cultured Mouse Microglial Cells Induced by Glutaraldehyde. in Journal of Membrane Biology
Springer, New York., 248(1), 117-123.
https://doi.org/10.1007/s00232-014-9748-7

Kalauzi A, Nikolić LM, Savić DZ, Radotić K. Cell Death Parameters as Revealed by Whole-Cell Patch-Clamp and Interval Weighted Spectra Averaging: Changes in Membrane Properties and Current Frequency of Cultured Mouse Microglial Cells Induced by Glutaraldehyde. in Journal of Membrane Biology. 2015;248(1):117-123.
doi:10.1007/s00232-014-9748-7 .

Kalauzi, Aleksandar, Nikolić, Ljiljana M., Savić, Danijela Z, Radotić, Ksenija, "Cell Death Parameters as Revealed by Whole-Cell Patch-Clamp and Interval Weighted Spectra Averaging: Changes in Membrane Properties and Current Frequency of Cultured Mouse Microglial Cells Induced by Glutaraldehyde" in Journal of Membrane Biology, 248, no. 1 (2015):117-123,
https://doi.org/10.1007/s00232-014-9748-7 . .

TY  - JOUR
AU  - Ristic, Aleksandar J
AU  - Savić, Danijela Z
AU  - Sokic, Dragoslav
AU  - Bogdanović Pristov, Jelena
AU  - Nestorov, Jelena
AU  - Baščarević, Vladimir
AU  - Raicević, Savo
AU  - Savić, Slobodan
AU  - Spasojević, Ivan
PY  - 2015
UR  - http://rimsi.imsi.bg.ac.rs/handle/123456789/898
AB  - ObjectiveTo examine antioxidative system in hippocampi of patients with mesial temporal lobe epilepsy associated with hippocampal sclerosis (mTLE-HS). MethodsActivity and levels of antioxidative enzymescatalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), manganese superoxide dismutase (MnSOD), and copper-zinc superoxide dismutase (CuZnSOD)were assessed in hippocampi of nine pharmacoresistant mTLE-HS patients (mean age 37.7[standard deviation] 6.6years) who underwent amygdalohippocampectomy, and in 10 hippocampi obtained via autopsy from five neurologically intact controls (mean age 34.49.0years). Subfield and cellular (neuron/astrocyte) distribution of CAT, GPx, and MnSOD was analyzed in detail using immunohistochemical staining. ResultsSclerotic hippocampi showed drastically increased activity of hydrogen peroxide-removing enzymes, CAT (p lt 0.001), GPx (p lt 0.001), and GR (p lt 0.001), and significantly higher protein levels of CAT (p=0.006), GPx (p=0.040), GR (p=0.024), and MnSOD (p=0.004), compared to controls. CAT immunofluorescence was located mainly in neurons in both controls and HS. Control hippocampi showed GPx staining in blood vessels and CA neurons. In HS, GPx-rich loci, representing bundles of astrocytes, emerged in different hippocampal regions, whereas the number of GPx-positive vessels was drastically decreased. Neurons with abnormal morphology and strong MnSOD immunofluorescence were present in all neuronal layers in HS. Small autofluorescent deposits, most likely lipofuscin, were observed, along with astrogliosis, in CA1 in HS. SignificanceAntioxidative system is upregulated in HS. This documents, for the first time, that epileptogenic hippocampi are exposed to oxidative stress. Our findings provide a basis for understanding the potential involvement of redox alterations in the pathology of epilepsy, and may open new pharmacologic perspectives for mTLE-HS treatment.
PB  - Wiley, Hoboken
T2  - Epilepsia
T1  - Hippocampal antioxidative system in mesial temporal lobe epilepsy
EP  - 799
IS  - 5
SP  - 789
VL  - 56
DO  - 10.1111/epi.12981
ER  - 

@article{
author = "Ristic, Aleksandar J and Savić, Danijela Z and Sokic, Dragoslav and Bogdanović Pristov, Jelena and Nestorov, Jelena and Baščarević, Vladimir and Raicević, Savo and Savić, Slobodan and Spasojević, Ivan",
year = "2015",
abstract = "ObjectiveTo examine antioxidative system in hippocampi of patients with mesial temporal lobe epilepsy associated with hippocampal sclerosis (mTLE-HS). MethodsActivity and levels of antioxidative enzymescatalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), manganese superoxide dismutase (MnSOD), and copper-zinc superoxide dismutase (CuZnSOD)were assessed in hippocampi of nine pharmacoresistant mTLE-HS patients (mean age 37.7[standard deviation] 6.6years) who underwent amygdalohippocampectomy, and in 10 hippocampi obtained via autopsy from five neurologically intact controls (mean age 34.49.0years). Subfield and cellular (neuron/astrocyte) distribution of CAT, GPx, and MnSOD was analyzed in detail using immunohistochemical staining. ResultsSclerotic hippocampi showed drastically increased activity of hydrogen peroxide-removing enzymes, CAT (p lt 0.001), GPx (p lt 0.001), and GR (p lt 0.001), and significantly higher protein levels of CAT (p=0.006), GPx (p=0.040), GR (p=0.024), and MnSOD (p=0.004), compared to controls. CAT immunofluorescence was located mainly in neurons in both controls and HS. Control hippocampi showed GPx staining in blood vessels and CA neurons. In HS, GPx-rich loci, representing bundles of astrocytes, emerged in different hippocampal regions, whereas the number of GPx-positive vessels was drastically decreased. Neurons with abnormal morphology and strong MnSOD immunofluorescence were present in all neuronal layers in HS. Small autofluorescent deposits, most likely lipofuscin, were observed, along with astrogliosis, in CA1 in HS. SignificanceAntioxidative system is upregulated in HS. This documents, for the first time, that epileptogenic hippocampi are exposed to oxidative stress. Our findings provide a basis for understanding the potential involvement of redox alterations in the pathology of epilepsy, and may open new pharmacologic perspectives for mTLE-HS treatment.",
publisher = "Wiley, Hoboken",
journal = "Epilepsia",
title = "Hippocampal antioxidative system in mesial temporal lobe epilepsy",
pages = "799-789",
number = "5",
volume = "56",
doi = "10.1111/epi.12981"
}

Ristic, A. J., Savić, D. Z., Sokic, D., Bogdanović Pristov, J., Nestorov, J., Baščarević, V., Raicević, S., Savić, S.,& Spasojević, I.. (2015). Hippocampal antioxidative system in mesial temporal lobe epilepsy. in Epilepsia
Wiley, Hoboken., 56(5), 789-799.
https://doi.org/10.1111/epi.12981

Ristic AJ, Savić DZ, Sokic D, Bogdanović Pristov J, Nestorov J, Baščarević V, Raicević S, Savić S, Spasojević I. Hippocampal antioxidative system in mesial temporal lobe epilepsy. in Epilepsia. 2015;56(5):789-799.
doi:10.1111/epi.12981 .

Ristic, Aleksandar J, Savić, Danijela Z, Sokic, Dragoslav, Bogdanović Pristov, Jelena, Nestorov, Jelena, Baščarević, Vladimir, Raicević, Savo, Savić, Slobodan, Spasojević, Ivan, "Hippocampal antioxidative system in mesial temporal lobe epilepsy" in Epilepsia, 56, no. 5 (2015):789-799,
https://doi.org/10.1111/epi.12981 . .

TY  - CONF
AU  - Ristic, Aleksandar J
AU  - Sokic, Dragoslav
AU  - Baščarević, Vladimir
AU  - Spasic, Snežana D
AU  - Vojvodic, Nikola M
AU  - Savić, Slobodan
AU  - Raicević, Savo
AU  - Kovacević, Masa
AU  - Savić, Danijela Z
AU  - Spasojević, Ivan
PY  - 2014
UR  - http://rimsi.imsi.bg.ac.rs/handle/123456789/789
AB  - Altered hippocampal metallome is strongly implicated in the pathology of mesial temporal lobe epilepsy with hippocampal sclerosis (mTLE-HS). We aimed to determine sodium, potassium, calcium, magnesium, iron, copper, manganese, and zinc concentration in epileptic human hippocampi.
PB  - Wiley-Blackwell, Hoboken
C3  - Epilepsia
T1  - Metallome of sclerotic hippocampi in patients with drug-resistant mesial temporal lobe epilepsy
EP  - 190
SP  - 190
VL  - 55
DO  - 10.1111/epi.12675
UR  - https://hdl.handle.net/21.15107/rcub_cer_1554
ER  - 

@conference{
author = "Ristic, Aleksandar J and Sokic, Dragoslav and Baščarević, Vladimir and Spasic, Snežana D and Vojvodic, Nikola M and Savić, Slobodan and Raicević, Savo and Kovacević, Masa and Savić, Danijela Z and Spasojević, Ivan",
year = "2014",
abstract = "Altered hippocampal metallome is strongly implicated in the pathology of mesial temporal lobe epilepsy with hippocampal sclerosis (mTLE-HS). We aimed to determine sodium, potassium, calcium, magnesium, iron, copper, manganese, and zinc concentration in epileptic human hippocampi.",
publisher = "Wiley-Blackwell, Hoboken",
journal = "Epilepsia",
title = "Metallome of sclerotic hippocampi in patients with drug-resistant mesial temporal lobe epilepsy",
pages = "190-190",
volume = "55",
doi = "10.1111/epi.12675",
url = "https://hdl.handle.net/21.15107/rcub_cer_1554"
}

Ristic, A. J., Sokic, D., Baščarević, V., Spasic, S. D., Vojvodic, N. M., Savić, S., Raicević, S., Kovacević, M., Savić, D. Z.,& Spasojević, I.. (2014). Metallome of sclerotic hippocampi in patients with drug-resistant mesial temporal lobe epilepsy. in Epilepsia
Wiley-Blackwell, Hoboken., 55, 190-190.
https://doi.org/10.1111/epi.12675
https://hdl.handle.net/21.15107/rcub_cer_1554

Ristic AJ, Sokic D, Baščarević V, Spasic SD, Vojvodic NM, Savić S, Raicević S, Kovacević M, Savić DZ, Spasojević I. Metallome of sclerotic hippocampi in patients with drug-resistant mesial temporal lobe epilepsy. in Epilepsia. 2014;55:190-190.
doi:10.1111/epi.12675
https://hdl.handle.net/21.15107/rcub_cer_1554 .

Ristic, Aleksandar J, Sokic, Dragoslav, Baščarević, Vladimir, Spasic, Snežana D, Vojvodic, Nikola M, Savić, Slobodan, Raicević, Savo, Kovacević, Masa, Savić, Danijela Z, Spasojević, Ivan, "Metallome of sclerotic hippocampi in patients with drug-resistant mesial temporal lobe epilepsy" in Epilepsia, 55 (2014):190-190,
https://doi.org/10.1111/epi.12675 .,
https://hdl.handle.net/21.15107/rcub_cer_1554 .

TY  - JOUR
AU  - Ristic, Aleksandar J
AU  - Sokic, Dragoslav
AU  - Baščarević, Vladimir
AU  - Spasic, Snežana D
AU  - Vojvodic, Nikola M
AU  - Savić, Slobodan
AU  - Raicević, Savo
AU  - Kovacević, Masa
AU  - Savić, Danijela Z
AU  - Spasojević, Ivan
PY  - 2014
UR  - http://rimsi.imsi.bg.ac.rs/handle/123456789/791
AB  - An altered metal and electrolyte profile has been implicated in the pathologic mechanisms of chronic epilepsy; however, no study has comprehensively measured hippocampal concentrations of these elements in patients with mesial temporal lobe epilepsy and hippocampal sclerosis (mTLE-HS). We therefore analyzed hippocampi of 24 patients with drug-resistant mTLE-HS (mean age 35.69.4years) who underwent anterior temporal lobe resection and amygdalohippocampectomy and 17 hippocampi obtained by autopsy from 13 controls (mean age 40.5 +/- 12.9years), using inductively coupled plasma optical emission spectrometry (ICP-OES). Epileptic hippocampi showed significantly lower concentrations (g/g of tissue) of copper (HS: 2.34 +/- 0.12; control [C]: 3.57 +/- 0.33; p lt 0.001), manganese (HS: 0.205 +/- 0.030; C: 0.409 +/- 0.064; p=0.004), and potassium (HS: 2,001 +/- 59; C: 2,322 +/- 61; p lt 0.001), and increased sodium levels (HS: 1,131 +/- 22; C: 1,040 +/- 25; p=0.010). Zinc, iron, calcium, and magnesium levels did not differ in HS and controls. In summary, copper and manganese levels are deficient, whereas iron level is unchanged in hippocampi from patients with mTLE-HS. Our results provide a basis for understanding the potential involvement of different metals and electrolytes in the pathology of HS. A PowerPoint slide summarizing this article is available for download in the Supporting Information section .
PB  - Wiley-Blackwell, Hoboken
T2  - Epilepsia
T1  - Metals and electrolytes in sclerotic hippocampi in patients with drug-resistant mesial temporal lobe epilepsy
EP  - E37
IS  - 5
SP  - E34
VL  - 55
DO  - 10.1111/epi.12593
ER  - 

@article{
author = "Ristic, Aleksandar J and Sokic, Dragoslav and Baščarević, Vladimir and Spasic, Snežana D and Vojvodic, Nikola M and Savić, Slobodan and Raicević, Savo and Kovacević, Masa and Savić, Danijela Z and Spasojević, Ivan",
year = "2014",
abstract = "An altered metal and electrolyte profile has been implicated in the pathologic mechanisms of chronic epilepsy; however, no study has comprehensively measured hippocampal concentrations of these elements in patients with mesial temporal lobe epilepsy and hippocampal sclerosis (mTLE-HS). We therefore analyzed hippocampi of 24 patients with drug-resistant mTLE-HS (mean age 35.69.4years) who underwent anterior temporal lobe resection and amygdalohippocampectomy and 17 hippocampi obtained by autopsy from 13 controls (mean age 40.5 +/- 12.9years), using inductively coupled plasma optical emission spectrometry (ICP-OES). Epileptic hippocampi showed significantly lower concentrations (g/g of tissue) of copper (HS: 2.34 +/- 0.12; control [C]: 3.57 +/- 0.33; p lt 0.001), manganese (HS: 0.205 +/- 0.030; C: 0.409 +/- 0.064; p=0.004), and potassium (HS: 2,001 +/- 59; C: 2,322 +/- 61; p lt 0.001), and increased sodium levels (HS: 1,131 +/- 22; C: 1,040 +/- 25; p=0.010). Zinc, iron, calcium, and magnesium levels did not differ in HS and controls. In summary, copper and manganese levels are deficient, whereas iron level is unchanged in hippocampi from patients with mTLE-HS. Our results provide a basis for understanding the potential involvement of different metals and electrolytes in the pathology of HS. A PowerPoint slide summarizing this article is available for download in the Supporting Information section .",
publisher = "Wiley-Blackwell, Hoboken",
journal = "Epilepsia",
title = "Metals and electrolytes in sclerotic hippocampi in patients with drug-resistant mesial temporal lobe epilepsy",
pages = "E37-E34",
number = "5",
volume = "55",
doi = "10.1111/epi.12593"
}

Ristic, A. J., Sokic, D., Baščarević, V., Spasic, S. D., Vojvodic, N. M., Savić, S., Raicević, S., Kovacević, M., Savić, D. Z.,& Spasojević, I.. (2014). Metals and electrolytes in sclerotic hippocampi in patients with drug-resistant mesial temporal lobe epilepsy. in Epilepsia
Wiley-Blackwell, Hoboken., 55(5), E34-E37.
https://doi.org/10.1111/epi.12593

Ristic AJ, Sokic D, Baščarević V, Spasic SD, Vojvodic NM, Savić S, Raicević S, Kovacević M, Savić DZ, Spasojević I. Metals and electrolytes in sclerotic hippocampi in patients with drug-resistant mesial temporal lobe epilepsy. in Epilepsia. 2014;55(5):E34-E37.
doi:10.1111/epi.12593 .

Ristic, Aleksandar J, Sokic, Dragoslav, Baščarević, Vladimir, Spasic, Snežana D, Vojvodic, Nikola M, Savić, Slobodan, Raicević, Savo, Kovacević, Masa, Savić, Danijela Z, Spasojević, Ivan, "Metals and electrolytes in sclerotic hippocampi in patients with drug-resistant mesial temporal lobe epilepsy" in Epilepsia, 55, no. 5 (2014):E34-E37,
https://doi.org/10.1111/epi.12593 . .

TY  - JOUR
AU  - Bajić, Aleksandar
AU  - Spasić, Mihajlo
AU  - Andjus, Pavle R
AU  - Savić, Danijela Z
AU  - Parabucki, Ana B
AU  - Nikolić-Kokić, Aleksandra
AU  - Spasojević, Ivan
PY  - 2013
UR  - http://rimsi.imsi.bg.ac.rs/handle/123456789/707
AB  - The effects of H2O2 are widely studied in cell cultures and other in vitro systems. However, such investigations are performed with the assumption that H2O2 concentration is constant, which may not properly reflect in vivo settings, particularly in redox-turbulent microenvironments such as mitochondria. Here we introduced and tested a novel concept of fluctuating oxidative stress. We treated C6 astroglial cells and primary astrocytes with H2O2, using three regimes of exposure - continuous, as well as fluctuating at low or high rate, and evaluated mitochondrial membrane potential and other parameters of mitochondrial activity - respiration, reducing capacity, and superoxide production, as well as intracellular ATP, intracellular calcium, and NF-kappa B activation. When compared to continuous exposure, fluctuating H2O2 induced a pronounced hyperpolarization in mitochondria, whereas the activity of electron transport chain appears not to be significantly affected. H2O2 provoked a decrease of ATP level and an increase of intracellular calcium concentration, independently of the regime of treatment. However, fluctuating H2O2 induced a specific pattern of large-amplitude fluctuations of calcium concentration. An impact on NF kappa B activation was observed for high rate fluctuations, whereas continuous and low rate fluctuating oxidative stress did not provoke significant effects. Presented results outline the (patho)physiological relevance of redox fluctuations.
PB  - Public Library Science, San Francisco
T2  - PLoS One
T1  - Fluctuating vs. Continuous Exposure to H2O2: The Effects on Mitochondrial Membrane Potential, Intracellular Calcium, and NF-kappa B in Astroglia
IS  - 10
VL  - 8
DO  - 10.1371/journal.pone.0076383
ER  - 

@article{
author = "Bajić, Aleksandar and Spasić, Mihajlo and Andjus, Pavle R and Savić, Danijela Z and Parabucki, Ana B and Nikolić-Kokić, Aleksandra and Spasojević, Ivan",
year = "2013",
abstract = "The effects of H2O2 are widely studied in cell cultures and other in vitro systems. However, such investigations are performed with the assumption that H2O2 concentration is constant, which may not properly reflect in vivo settings, particularly in redox-turbulent microenvironments such as mitochondria. Here we introduced and tested a novel concept of fluctuating oxidative stress. We treated C6 astroglial cells and primary astrocytes with H2O2, using three regimes of exposure - continuous, as well as fluctuating at low or high rate, and evaluated mitochondrial membrane potential and other parameters of mitochondrial activity - respiration, reducing capacity, and superoxide production, as well as intracellular ATP, intracellular calcium, and NF-kappa B activation. When compared to continuous exposure, fluctuating H2O2 induced a pronounced hyperpolarization in mitochondria, whereas the activity of electron transport chain appears not to be significantly affected. H2O2 provoked a decrease of ATP level and an increase of intracellular calcium concentration, independently of the regime of treatment. However, fluctuating H2O2 induced a specific pattern of large-amplitude fluctuations of calcium concentration. An impact on NF kappa B activation was observed for high rate fluctuations, whereas continuous and low rate fluctuating oxidative stress did not provoke significant effects. Presented results outline the (patho)physiological relevance of redox fluctuations.",
publisher = "Public Library Science, San Francisco",
journal = "PLoS One",
title = "Fluctuating vs. Continuous Exposure to H2O2: The Effects on Mitochondrial Membrane Potential, Intracellular Calcium, and NF-kappa B in Astroglia",
number = "10",
volume = "8",
doi = "10.1371/journal.pone.0076383"
}

Bajić, A., Spasić, M., Andjus, P. R., Savić, D. Z., Parabucki, A. B., Nikolić-Kokić, A.,& Spasojević, I.. (2013). Fluctuating vs. Continuous Exposure to H2O2: The Effects on Mitochondrial Membrane Potential, Intracellular Calcium, and NF-kappa B in Astroglia. in PLoS One
Public Library Science, San Francisco., 8(10).
https://doi.org/10.1371/journal.pone.0076383

Bajić A, Spasić M, Andjus PR, Savić DZ, Parabucki AB, Nikolić-Kokić A, Spasojević I. Fluctuating vs. Continuous Exposure to H2O2: The Effects on Mitochondrial Membrane Potential, Intracellular Calcium, and NF-kappa B in Astroglia. in PLoS One. 2013;8(10).
doi:10.1371/journal.pone.0076383 .

Bajić, Aleksandar, Spasić, Mihajlo, Andjus, Pavle R, Savić, Danijela Z, Parabucki, Ana B, Nikolić-Kokić, Aleksandra, Spasojević, Ivan, "Fluctuating vs. Continuous Exposure to H2O2: The Effects on Mitochondrial Membrane Potential, Intracellular Calcium, and NF-kappa B in Astroglia" in PLoS One, 8, no. 10 (2013),
https://doi.org/10.1371/journal.pone.0076383 . .