Enhanced mtDNA repair capacity protects pulmonary artery endothelial cells from oxidant-mediated death
Departments of 1 Cell Biology and Neuroscience and 2 Pharmacology, College of Medicine, University of South Alabama, Mobile, Alabama 36688; and 3 Wells Center for Pediatric Research, Indiana University Medical School, Indianapolis, Indiana 46202 In rat cultured pulmonary arterial (PA), microvascu...
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Veröffentlicht in: | American journal of physiology. Lung cellular and molecular physiology 2002-07, Vol.283 (1), p.205-L210 |
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Zusammenfassung: | Departments of 1 Cell Biology and Neuroscience and
2 Pharmacology, College of Medicine, University of
South Alabama, Mobile, Alabama 36688; and 3 Wells Center
for Pediatric Research, Indiana University Medical School,
Indianapolis, Indiana 46202
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.
mitochondrial deoxyribonucleic acid; xanthine oxidase; Ogg1 ; cytotoxicity |
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ISSN: | 1040-0605 1522-1504 |
DOI: | 10.1152/ajplung.00443.2001 |