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Mitochondrial DNA integrity may be a determinant of endothelial barrier properties in oxidant-challenged rat lungs.
- Source :
- American Journal of Physiology: Lung Cellular & Molecular Physiology; Dec2011, Vol. 301, pL892-L898, 7p
- Publication Year :
- 2011
-
Abstract
- In cultured pulmonary artery endothelial cells and other cell types, overexpression of mt-targeted DNA repair enzymes protects against oxidant-induced mito-chondrial DNA (mtDNA) damage and cell death. Whether mtDNA integrity governs functional properties of the endothelium in the intact pulmonary circulation is unknown. Accordingly, the present study used isolated, buffer-perfused rat lungs to determine whether fusion proteins targeting 8-oxoguanine DNA glycosylase 1 (Ogg I) or endo-nuclease III (Endo III) to mitochondria attenuated mtDNA damage and vascular barrier dysfunction evoked by glucose oxidase (GOX)-generated hydrogen peroxide. We found that both Endo III and Ogg 1 fusion proteins accumulated in lung cell mitochondria within 30 mm of addition to the perfusion medium. Both constructs prevented GOX-induced increases in the vascular filtration coefficient. Although GOX-induced nuclear DNA damage could not be detected, quantitative Southern blot analysis revealed substantial GOX-induced oxidative mtDNA damage that was prevented by pretreatment with both fusion proteins. The Ogg1 construct also reversed preexisting GOX- induced vascular barrier dysfunction and oxidative mtDNA damage. Collectively, these findings support the ideas that mtDNA is a sentinel molecule governing lung vascular barrier responses to oxidant stress in the intact lung and that the mtDNA repair pathway could be a target for pharmacological intervention in oxidant lung injury. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 10400605
- Volume :
- 301
- Database :
- Complementary Index
- Journal :
- American Journal of Physiology: Lung Cellular & Molecular Physiology
- Publication Type :
- Academic Journal
- Accession number :
- 69614242
- Full Text :
- https://doi.org/10.1152/ajplung.00210.2011