Hypoxia promotes oxidative base modifications in the pulmonary artery endothelial cell VEGF gene.

Abstract

SPECIFIC AIMSThe conclusion that mitochondrially derived oxidants play a role in hypoxic signal transduction has remained controversial in part because of doubts concerning methods of free radical detection and because of theoretical objections to the notion that mitochondria are capable of increasing oxidant generation in a low oxygen environment. To help resolve this controversy, the present study tested the hypothesis that hypoxia causes oxidative modifications in mtDNA or in the nuclear vascular endothelial cell growth factor (VEGF) gene, the latter of which should serve as a negative control based on the relatively insensitive nuclear genome to oxidant stress in comparison to that in the mitochondria.PRINCIPAL FINDINGS1. Hypoxia causes an oxidant stress in pulmonary artery endothelial cells as detected by fluorescence of dichlorfluorescein (DCF)We used rat cultured main pulmonary artery cells (PAECs) as the model system for these studies because they are important in the integrated pulmonary vascular...