Heme oxygenase-1 (HO-1), which catalyzes the degradation of heme to iron, carbon monoxide, and biliverdin, performs a cytoprotective function. Previous studies on the crystal structure of the human and rat HO-1 in complex with heme showed that Gly139His (G139H) and Gly143His (G143H) mutants have no HO activity. In the present study, we reported the effect of the G139H, G143H, and Ser142His mutants of mouse HO-1 on the HO reaction in vivo and in vitro. In vitro, of the mutant transfectants, only Ser142His catalyzed degradation of heme, retaining 31.7% of the wild-type mouse HO-1 activity, whereas G139H and G143H mutants exhibited no activity. In vivo, only Tg HO-1 G143H females presented with anemia, enlarged spleen and tissue iron overload, which was similar to HO-1(-/-) mice. The results suggested the critical role of Gly139 and Gly143 in maintaining HO-1 activity in vitro and the critical role of Gly143 in maintaining HO-1 activity in vivo.
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