Effects of hypoxia on mnsod expression in mouse lung.
Russell, William J., Ye-Shih Ho, Gregory Parish, and Robert M.
Jackson.
Birmingham VA Medical Center and University of AL at Birmingham,
Birmingham, AL and Wayne State University, Detroit, MI
APStracts 2:0080L, 1995.
Mitochondrial, manganese-containing SOD (MnSOD) is located at the
primary site of oxygen metabolism, and its expression may be
regulated by changes in oxygen level. We hypothesized that lung MnSOD
expression and promoter activity would decrease in response to
hypoxia. We tested effects of hypoxia (10% O2 at sea level for 7d) on
CAT reporter and MnSOD gene expression in transgenic mice. The
transgene consisted of a 3.3 kb portion of the rat MnSOD gene 5'
flanking region coupled to a chloramphenicol acetyltransferase (CAT)
reporter gene. Lung MnSOD activity in male (but not female) mice
decreased significantly after hypoxia exposure. The decrease in MnSOD
enzymatic activity in male mice was specific. Neither total SOD nor
G6-PD activity decreased significantly in hypoxia. CAT protein
expression decreased in transgenic males exposed to hypoxia, while
CAT protein expression in hypoxic transgenic females remained
comparable to controls. The mRNA for both the native MnSOD and the
MnSOD-CAT reporter genes remained constant after hypoxia, as did
CuZnSOD and G6-PD mRNA's.
Received 30 August 1994; accepted in final form 10 April 1995.
APS Manuscript Number L257-4.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 16 May 1995.