Divergent Effects of Hypoxia and Oxidants on Mitochondrial Superoxide Dismutase (MnSOD) Gene Expression

Abstract

We reported previously that lung cellular hypoxia downregulated superoxide dismutase expression in alveolar type II (ATII) epithelial cells (Jackson et al. 1996). ATII cells were exposed in vitro to air (controls) or 2.5% O2 (hypoxia) for 24 hours. MnSOD mRNA and CuZnSOD mRNA expression were measured by quantitative RT-PCR. MnSOD and CuZnSOD mRNA expression in ATII cells both decreased significantly after one day in hypoxia. The decrease in MnSOD mRNA (-69%) was greater than that in CuZnSOD mRNA (-48%). ATII cell SP-A transcript expression remained constant. MnSOD (-52%) and CuZnSOD (-54%) mRNA expression decreased similarly in lung fibroblasts cultured in hypoxia. The half-life of the MnSOD mRNA measured in lung fibroblasts exposed to air or hypoxia for 24h decreased significantly from 4.8±0.4 to 3.8±0.7 hours (-21%). The half-life for the CuZnSOD decreased significantly from 4.0±0.9 to 2.3±0.2 hours (-43%). MnSOD protein expression (assessed on western blots) also decreased after exposure of the cells to hypoxia (1% O2 for 24 hours). The present studies were designed to learn whether oxidant stress upregulated expression of MnSOD gene expression in epithelial cells