AJP - Lung Cellular and Molecular Physiology, Vol 269, Issue 2 221-L226, Copyright © 1995 by American Physiological Society
Effects of hypoxia on MnSOD expression in mouse lung
W. J. Russell, Y. S. Ho, G. Parish and R. M. Jackson
Birmingham Veterans Affairs Medical Center, Alabama, USA.
Mitochondrial manganese-containing SOD (MnSOD) is located at the primary
site of O2 metabolism, and its expression may be regulated by changes in O2
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 7 days) on chloramphenicol acetyltransferase (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 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 glucose-6-phosphate dehydrogenase (G-6-PDH) 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 with controls. The mRNA for both the
native MnSOD and the MnSOD-CAT reporter genes remained constant after
hypoxia, as did CuZnSOD and G-6-PDH mRNAs.
