Induction of heme oxygenase-1 as a response in sensing the signals evoked by distinct nitric oxide donors

被引:54
作者
Hara, E
Takahashi, K
Takeda, K
Nakayama, M
Yoshizawa, M
Fujita, H
Shirato, K
Shibahara, S
机构
[1] Tohoku Univ, Sch Med, Dept Mol Biol & Appl Physiol, Aoba Ku, Sendai, Miyagi 9808575, Japan
[2] Tohoku Univ, Sch Med, Dept Internal Med, Aoba Ku, Sendai, Miyagi 9808575, Japan
关键词
heme oxygenase; sodium nitroprusside; nitric oxide; oxidative stress; bilirubin;
D O I
10.1016/S0006-2952(99)00097-0
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
To gain insights into the cellular responses evoked by nitric oxide (NO), we have studied the effects of NO donors with distinct chemistries on the expression of heme oxygenase-l mRNA by northern blot analysis. The expression levels of heme oxygenase-l mRNA were increased significantly in DLD-1 human colorectal adenocarcinoma cells by treatment with each of three NO donors: sodium nitroprusside (SNP), S-nitroso L-glutathione (GSNO), and 3-morpholinosydnonimine (SIN-1). A combination of SIN-1 plus SNP or GSNO additively increased heme oxygenase-l mRNA expression, whereas synergistic induction was seen with SNP plus GSNO. The SNP-mediated induction was not affected noticeably by extracellular superoxide dismutase, catalase, or mannitol, while the induction by SIN-1 was attenuated by superoxide dismutase. Thus, the SNP-mediated induction of heme oxygenase-l mRNA expression may be independent of reactive oxygen species, and the induction by SIN-1 is mediated partly by peroxynitrite, which is generated by immediate reaction of NO and superoxide anion. Transient transfection assays suggested that treatment with SNP, hut not with GSNO or SIN-1, increased the expression of a reporter gene through a cis-acting element, including the cadmium-responsive element, of the human heme oxygenase-l gene. These results suggest that SNP induces heme oxygenase-l mRNA expression through a mechanism different from that for GSNO or SIN-1. We therefore propose that induction of heme oxygenase-l represents a common cellular response in sensing the signals evoked by distinct: NO donors. (C) 1999 Elsevier Science Inc.
引用
收藏
页码:227 / 236
页数:10
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