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Oxidative Medicine and Cellular Longevity
Volume 2013 (2013), Article ID 159567, 9 pages
http://dx.doi.org/10.1155/2013/159567
Research Article

Dual Phases of Respiration Chain Defect-Augmented mROS-Mediated mCa2+ Stress during Oxidative Insult in Normal and ρ0 RBA1 Astrocytes

1Department of Neurology, Keelung Medical Center, Chang Gung Memorial Hospital, Keelung, Taiwan
2Department of Medicine, Chang Gung University, Tao-Yuan, Taiwan
3Department of Surgery, Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan
4Department of Neurosurgery, Taipei City Hospital, Zhongxiao Branch, Taipei, Taiwan
5Department of Physiology and Pharmacology, College of Medicine, Chang Gung University, 259 Wen-Hwa 1st Road, Kwei-Shan, Tao-Yuan 333, Taiwan

Received 12 December 2012; Accepted 8 January 2013

Academic Editor: Sumitra Miriyala

Copyright © 2013 Tsung-I Peng et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Mitochondrial respiratory chain (RC) deficits, resulting in augmented mitochondrial ROS (mROS) generation, underlie pathogenesis of astrocytes. However, mtDNA-depleted cells (ρ0) 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 (mCa2+) were compared between two different astrocyte cell lines, control and ρ0 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 ρ0 astrocytes, respectively. In contrast to RBA-1, 30 minutes after 20 mM H2O2 exposure, ρ0 astrocytes formed marked plasma membrane blebs, lost the ability to retain Mito-R, and showed condensation of nuclei. Importantly, H2O2-induced ROS and accompanied mCa2+ elevation in control showed higher levels than ρ0 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 mCa2+ stress during severe oxidative insult.