Reduced stress defense in heme oxygenase 1-deficient cells

被引：1120

作者：

Poss, KD

Tonegawa, S

机构：

[1] Howard Hughes Medical Institute, Center for Learning and Memory, Center for Cancer Research, Cambridge

[2] Center for Cancer Research, E17-346, Massachusetts Inst. of Technology, Cambridge, MA 02139

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 1997年 / 94卷 / 20期

关键词：

D O I：

10.1073/pnas.94.20.10925

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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 irt vivo results provide genetic evidence that up-regulation of Hmox1 serves as an adaptive mechanism to protect cells from oxidative damage during stress.

引用

页码：10925 / 10930

页数：6

共 39 条

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