Fluctuating vs. continuous exposure to H₂O₂: the effects on mitochondrial membrane potential, intracellular calcium, and NF-κB in astroglia.
Fluctuating vs. continuous exposure to H₂O₂: the effects on mitochondrial membrane potential, intracellular calcium, and NF-κB in astroglia.
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DOI：
10.1371/journal.pone.0076383
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Spasojević I
中科院分区：
文献类型：
--
作者：
Bajić A;Spasić M;Andjus PR;Savić D;Parabucki A;Nikolić-Kokić A;Spasojević I
H2O2的作用在细胞培养和其他体外系统中被广泛研究。然而，这些研究是在假设H2O2浓度恒定的情况下进行的，这可能无法正确反映体内环境，特别是在氧化还原湍流微环境（如线粒体）中。在这里，我们介绍并测试了波动氧化应激的新概念。我们用H2O2处理C6星形胶质细胞和原代星形胶质细胞，使用三种暴露方案-连续暴露，以及低或高速率波动暴露，并评估线粒体膜电位和线粒体活性的其他参数-呼吸，还原能力，超氧化物产生，以及细胞内ATP，细胞内钙和NF-κ b活化。与连续暴露相比，波动的H2O2诱导线粒体明显的超极化，而电子传递链的活性似乎没有受到显著影响。H2O2引起ATP水平的降低和细胞内钙浓度的增加，与治疗方案无关。然而，波动的H2O2诱导了钙浓度的特定模式的大幅波动。观察到高速率波动对NF-κB活化的影响，而连续和低速率波动氧化应激对NF-κB活化没有显著影响。提出的结果概述了氧化还原波动的（病理）生理相关性。
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-κB 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-κB 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.
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DOI：
10.1042/bj20081386
发表时间：
2009-01-01
期刊：
The Biochemical journal
影响因子：
--
作者：
Murphy MP
通讯作者：
Murphy MP
影响因子：
3.5
作者：
Halliwell, B
通讯作者：
Halliwell, B
DOI：
10.1016/j.bbagen.2008.03.010
发表时间：
2008-06-01
影响因子：
3
作者：
Makino, Nobuo;Mise, Takeshi;Sagara, Jun-ichi
通讯作者：
Sagara, Jun-ichi
影响因子：
20.1
作者：
De Keulenaer, GW;Chappell, DC;Griendling, KK
通讯作者：
Griendling, KK
影响因子：
3.3
作者：
Choi, Jung-Jin;Choi, Jiwoong;Kim, Won-Ki
通讯作者：
Kim, Won-Ki