Dual Phases of Respiration Chain Defect-Augmented mROS-Mediated mCa(2+) Stress during Oxidative Insult in Normal and rho(0) RBA1 Astrocytes

作者：Peng Tsung I; Lin Muh Shi^*; Jou Mei Jie

来源：Oxidative Medicine and Cellular Longevity, 2013, 2013: 159567.

DOI：10.1155/2013/159567

Mitochondrial respiratory chain (RC) deficits, resulting in augmented mitochondrial ROS (mROS) generation, underlie pathogenesis of astrocytes. However, mtDNA-depleted cells (rho(0)) lacking RC have been reported to be either sensitive or resistant to apoptosis. In this study, we sought to determine the effects of RC-enhanced mitochondrial stress following oxidative insult. Using noninvasive fluorescence probe-coupled laser scanning imaging microscopy, the ability to resist oxidative stress and levels of mROS formation and mitochondrial calcium (mCa(2+)) were compared between two different astrocyte cell lines, control and rho(0) astrocytes, over time upon oxidative stress. Our results showed that the cytoplasmic membrane becomes permeated with YO-PRO-1 dye at 150 and 130 minutes in RBA-1 and rho(0) astrocytes, respectively. In contrast to RBA-1, 30 minutes after 20 mM H2O2 exposure, rho(0) astrocytes formed marked plasma membrane blebs, lost the ability to retain Mito-R, and showed condensation of nuclei. Importantly, H2O2-induced ROS and accompanied mCa(2+) elevation in control showed higher levels than rho(0) at early time point but vice versa at late time point. Our findings underscore dual phase of RC-defective cells harboring less mitochondrial stress due to low RC activity during short-term oxidative stress but augmented mROS-mediated mCa(2+) stress during severe oxidative insult.

• 出版日期2013
• 单位长春大学