EXPRESSION OF MANGANESE SUPEROXIDE-DISMUTASE IS NOT ALTERED IN TRANSGENIC MICE WITH ELEVATED LEVEL OF COPPER-ZINC SUPEROXIDE-DISMUTASE

In evaluating the relative expression of copper-zinc and manganese sup eroxide dismutase (CuZnSOD and MnSOD) in vivo in states like Down synd rome in which one dismutase is present at increased levels, we measure d activities of both enzymes, in tissues of control and transgenic mic e constitutively expressing increased levels of CuZnSOD, during exposu re to normal and elevated oxygen tensions. Using SOD gel electrophores is assay, CuZnSOD and MnSOD activities of brain, lung, heart, kidney, and liver from mice exposed to either normal (21%) or elevated (>99% o xygen, 630 torr) oxygen tensions for 120 h were compared. Whereas CuZn SOD activity was elevated in tissues of transgenic relative to control mice under both normoxic or hyperoxic conditions, MnSOD activities in organs of transgenic mice were remarkably similar to those of control s under both conditions. To confirm the accuracy of this method in qua ntitating MnSOD relative to CuZnSOD expression, two other methods were utilized. In lung, which is the organ exposed to the highest oxygen t ension during ambient hyperoxia, a sensitive, specific ELISA for MnSOD was used. Again, MnSOD protein was not different in transgenic relati ve to control mice during exposure to air or hyperoxia. In addition, l ung MnSOD protein was not changed significantly by exposure to hyperox ia in either group. In kidney, a mitochondrion-rich organ, SOD assay, before and after inactivation of CuZnSOD with diethyldithiocarbamate, was used. MnSOD activity was not different in organs from air-exposed transgenic relative to control mice. The data indicated that expressio n of MnSOD in vivo was not affected by overexpression of the CuZnSOD a nd, therefore, the two enzymes are probably regulated independently.