期刊
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
卷 283, 期 1, 页码 L205-L210出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajplung.00443.2001
关键词
mitochondrial deoxyribonucleic acid; xanthine oxidase; Ogg1; cytotoxicity
资金
- NCI NIH HHS [CA-76643, CA-75426] Funding Source: Medline
- NHLBI NIH HHS [HL-66299, HL-58243] Funding Source: Medline
- NIA NIH HHS [AG-12422] Funding Source: Medline
- NIEHS NIH HHS [ES-03456, ES-05865] Funding Source: Medline
- NINDS NIH HHS [NS-38506] Funding Source: Medline
In rat cultured pulmonary arterial (PA), microvascular, and venous endothelial cells (ECs), the rate of mitochondrial (mt) DNA repair is predictive of the severity of xanthine oxidase (XO)-induced mtDNA damage and the sensitivity to XO-mediated cell death. To examine the importance of mtDNA damage and repair more directly, we determined the impact of mitochondrial overexpression of the DNA repair enzyme, Ogg1, on XO-induced mtDNA damage and cell death in PAECs. PAECs were transiently transfected with an Ogg1-mitochondrial targeting sequence construct. Mitochondria-selective overexpression of the transgene product was confirmed microscopically by the observation that immunoreactive Ogg1 colocalized with a mitochondria-specific tracer and, with an oligonucleotide cleavage assay, by a selective enhancement of mitochondrial Ogg1 activity. Overexpression of Ogg1 protected against both XO-induced mtDNA damage, determined by quantitative Southern analysis, and cell death as assessed by trypan blue exclusion and MTS assays. These findings show that mtDNA damage is a direct cause of cell death in XO-treated PAECs.
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