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Reduced stress defense in heme oxygenase 1-deficient cells
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Contributed by Susumu Tonegawa

Abstract
Stressed mammalian cells up-regulate heme oxygenase 1 (Hmox1; EC 1.14.99.3), which catabolizes heme to biliverdin, carbon monoxide, and free iron. To assess the potential role of Hmox1 in cellular antioxidant defense, we analyzed the responses of cells from mice lacking functional Hmox1 to oxidative challenges. Cultured Hmox1−/− embryonic fibroblasts demonstrated high oxygen free radical production when exposed to hemin, hydrogen peroxide, paraquat, or cadmium chloride, and they were hypersensitive to cytotoxicity caused by hemin and hydrogen peroxide. Furthermore, young adult Hmox1−/− mice were vulnerable to mortality and hepatic necrosis when challenged with endotoxin. Our in vitro and in vivo results provide genetic evidence that up-regulation of Hmox1 serves as an adaptive mechanism to protect cells from oxidative damage during stress.
Footnotes
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↵* To whom reprint requests should be addressed at: Center for Cancer Research, E17-346, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139. e-mail: kdposs{at}mit.edu.
ABBREVIATIONS
- Hmox,
- heme oxygenase;
- E12.5,
- embryonic day 12.5;
- MEFs,
- murine embryonic fibroblasts;
- LPS,
- lipopolysaccharide
- Accepted July 16, 1997.
- Copyright © 1997, The National Academy of Sciences of the USA