人源 OXR1 通过调控涉及 p21 的抗氧化途径来维持线粒体 DNA 完整性并拮抗过氧化氢诱导的氧化应激。

Human OXR1 maintains mitochondrial DNA integrity and counteracts hydrogen peroxide-induced oxidative stress by regulating antioxidant pathways involving p21.

机构信息

Department of Microbiology, University of Oslo, N-0424 Oslo, Norway; Department of Medical Biochemistry, Oslo University Hospital, University of Oslo, N-0424 Oslo, Norway.

Department of Microbiology, University of Oslo, N-0424 Oslo, Norway.

出版信息

Free Radic Biol Med. 2014 Dec;77:41-8. doi: 10.1016/j.freeradbiomed.2014.09.003. Epub 2014 Sep 16.

DOI:10.1016/j.freeradbiomed.2014.09.003

PMID:25236744

Abstract

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.

摘要

氧化还原基因 1（OXR1）通过未知途径防止氧化应激诱导的细胞死亡。在这里，人源 OXR1（hOXR1）的消耗使几种人类细胞系对过氧化氢诱导的氧化应激敏感，降低了 mtDNA 完整性，并增加了细胞凋亡。相比之下，在缺乏 mtDNA 的细胞中消耗 hOXR1 并没有导致 ROS 或活力的显著变化，这表明 OXR1 防止细胞内过氧化氢诱导的氧化应激水平增加，以避免氧化 mtDNA 损伤和 ROS 形成的恶性循环。此外，在 hOXR1 耗尽的细胞中，p21 和抗氧化基因 GPX2 和 HO-1 的表达减少。总之，这些数据表明，人类 OXR1 通过 p21 信号通路上调抗氧化基因的表达，以抑制过氧化氢诱导的氧化应激并维持 mtDNA 完整性。