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Fluctuating vs. Continuous Exposure to H2O2: The Effects on Mitochondrial Membrane Potential, Intracellular Calcium, and NF-kappa B in Astroglia

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2013
704.pdf (4.724Mb)
Authors
Bajić, Aleksandar
Spasić, Mihajlo
Andjus, Pavle R
Savić, Danijela Z
Parabucki, Ana B
Nikolić-Kokić, Aleksandra
Spasojević, Ivan
Article (Published version)
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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.

Keywords:
Astrocytes / Autophagy / Lipolysis / Nutrient deprivation / Mitochondrial membrane potential
Source:
PLoS One, 2013, 8, 10
Publisher:
  • Public Library Science, San Francisco
Funding / projects:
  • Biomarkers in neurodegenerative and malignant processes (RS-41005)
  • Molecular mechanisms of redox signalling in homeostasis: adaptation and pathology (RS-173014)
  • Cellular and molecular basis of neuroinflamation: potential targets for translational medicine and therapy (RS-41014)

DOI: 10.1371/journal.pone.0076383

ISSN: 1932-6203

PubMed: 24124554

WoS: 000325489100111

Scopus: 2-s2.0-84885033968
[ Google Scholar ]
20
14
URI
http://rimsi.imsi.bg.ac.rs/handle/123456789/707
Collections
  • Radovi istraživača / Researchers’ publications
Institution/Community
Institut za multidisciplinarna istraživanja
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 . .

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