EFFECTS OF HYPOXIA ON MNSOD EXPRESSION IN MOUSE LUNG

Mitochondrial manganese-containing SOD (MnSOD) is located at the prima ry site of O-2 metabolism, and its expression may be regulated by chan ges in O-2 level. We hypothesized that lung MnSOD expression and promo ter activity would decrease in response to hypoxia. We tested effects of hypoxia (10% O-2 at sea level for 7 days) on chloramphenicol acetyl transferase (CAT) reporter and MnSOD gene expression in transgenic mic e. 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 ex posure. The decrease in MnSOD enzymatic activity in male mice was spec ific. 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 ex pression in hypoxic transgenic females remained comparable with contro ls. The mRNA for both the native MnSOD and the MnSOD-CAT reporter gene s remained constant after hypoxia, as did CuZnSOD and G-6-PDH mRNAs.