Enhanced mtDNA repair capacity protects pulmonary artery endothelial cells from oxidant-mediated death
| Autor: | Susan P. LeDoux, Mark R. Kelley, Valentina I. Grishko, Allison W. Dobson, Glenn L. Wilson, Mark N. Gillespie |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
Pulmonary and Respiratory Medicine
Xanthine Oxidase Programmed cell death Mitochondrial DNA DNA Repair Endothelium Physiology DNA repair Pulmonary Artery Biology Transfection DNA Mitochondrial Rats Sprague-Dawley chemistry.chemical_compound Physiology (medical) medicine Animals Xanthine oxidase N-Glycosyl Hydrolases Cells Cultured Cell Death Cell Biology Oxidants Molecular biology Mitochondria Rats Endothelial stem cell Phenotype medicine.anatomical_structure DNA-Formamidopyrimidine Glycosylase Biochemistry chemistry Pulmonary Veins Trypan blue Endothelium Vascular |
| Zdroj: | American Journal of Physiology-Lung Cellular and Molecular Physiology. 283:L205-L210 |
| ISSN: | 1522-1504 1040-0605 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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