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

2013
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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Show full item recordAbstract
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 potentialSource:
PLoS One, 2013, 8, 10Publisher:
- 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
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Institut za multidisciplinarna istraživanjaTY - 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 . .