Journal
FREE RADICAL BIOLOGY AND MEDICINE
Volume 77, Issue -, Pages 41-48Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.freeradbiomed.2014.09.003
Keywords
DNA damage; Mitochondria; Oxidative stress; ROS; OXR1; p21; HO-1; GPX2; Free radicals
Funding
- Research Council of Norway
- Norwegian Cancer Society
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The oxidation resistance gene 1 (OXR1) prevents oxidative stress-induced cell death by an unknown pathway. Here, depletion of human OXR1 (hOXR1) sensitized several human cell lines to hydrogen peroxide-induced oxidative stress, reduced mtDNA integrity, and increased apoptosis. In contrast, depletion of hOXR1 in cells lacking mtDNA showed no significant change in ROS or viability, suggesting that OXR1 prevents intracellular hydrogen peroxide-induced increase in oxidative stress levels to avoid a vicious cycle of increased oxidative mtDNA damage and ROS formation. Furthermore, expression of p21 and the antioxidant genes GPX2 and HO-1 was reduced in hOXR1-depleted cells. In sum, these data reveal that human OXR1 upregulates the expression of antioxidant genes via the p21 signaling pathway to suppress hydrogen peroxide-induced oxidative stress and maintain mtDNA integrity. (C) 2014 The Authors. Published by Elsevier Inc.
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