Cooperative induction of c-fos and heme oxygenase gene products under oxidative stress in human fibroblastic cells

被引:22
作者
Numazawa, S [1 ]
Yamada, H [1 ]
Furusho, A [1 ]
Nakahara, T [1 ]
Oguro, T [1 ]
Yoshida, T [1 ]
机构
[1] Showa Univ, Sch Pharmaceut Sci, Dept Biochem Toxicol, Shinagawa Ku, Tokyo 142, Japan
关键词
D O I
10.1006/excr.1997.3825
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Heme oxygenase-1 is a stress responsive enzyme and implicated in a protective function of cellular damage. We investigated cellular events leading to the heme oxygenase-1 gene expression induced by sublethal concentrations of glutathione depletors, phorone and diethyl maleate, in human fibroblastic cells. Accumulation of heme oxygenase-1 mRNA by glutathione depletors was canceled by simultaneous treatment with cycloheximide, an inhibitor of protein synthesis; however, the inhibitory effect decreased when the inhibitor was added 30 min later. Among the inducible early response genes, the c-fos expression was significantly elevated with a peak at 30 min after the agents. Accumulation of heme oxygenase-1 and c-fos transcripts was abrogated in cells pretreated with 1,4-diazabicyclo[2.2.2]octane, an oxygen-free radical quencher. Decrease in glutathione levels preferentially activated extracellular-signal regulated kinases rather than other stress-activated protein kinases such as c-Jun N-terminal kinases and p38 MAP kinase. Pretreatment of cells with PD 98059, an inhibitor of the extracellular-signal regulated kinase cascade, or the c-fos antisense oligodeoxynucleotide inhibited the heme oxygenase-1 induction elicited by glutathione depletion. These observations indicated that c-Fos protein plays a role in heme oxygenase-l gene expression induced by glutathione depletion-mediated oxidative stress in human fibroblasts. (C) 1997 Academic Press.
引用
收藏
页码:434 / 444
页数:11
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