Effects of hypoxia on expression of superoxide dismutases in
cultured atii cells and lung fibroblasts.
Jackson, Robert M., Gregory Parish, and Ye-Shih Ho.
Birmingham VA Medical Center, Birmingham, AL 35223, University of
Alabama at Birmingham, Birmingham, AL 35294 and Institute of Chemical
Toxicology, Wayne State University, Detroit, MI 48201
APStracts 3:0157L, 1996.
This study investigated whether hypoxia affected the expression of
mitochondrial, manganese-containing superoxide dismutase (MnSOD) and
the cytosolic, copper and zinc-containing superoxide dismutase
(CuZnSOD) in alveolar type II epithelial (ATII) cells and lung
fibroblasts. Cells were exposed in vitro to air (controls) or 2.5% O2
(hypoxia) for 24 hours. MnSOD 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 5.8+/-0.1 to 3.8+/-0.7 hours (-34%). The
half-life for the CuZnSOD decreased significantly from 4.0+/-0.3 to
2.4+/-0.1 hours (-40%). Neither MnSOD nor CuZnSOD protein expression
in ATII cells changed significantly in hypoxia. Hypoxia decreases
expression of MnSOD and CuZnSOD mRNA's in ATII cells and lung
fibroblasts in part by decreasing stability of the mRNA transcripts.
Received 26 April 1996; accepted in final form 15 August 1996.
APS Manuscript Number L127-6.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 7 October 1996