Role of mitochondrial respiratory chain in neuronal toxicity due to carbon monoxide poisoning

线粒体呼吸链在一氧化碳中毒神经元毒性中的作用

基本信息

批准号：
17590586
负责人：
HARA Shuichi
金额：
$ 2.3万
依托单位：
Tokyo Medical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2006
项目状态：
已结题

项目摘要

The mitochondrial respiration chain is one of pathways associated with reactive oxygen species (ROS) generation in the cell. Interruption of this chain results in stimulation of ROS generation. In this study, it was examined whether the mitochondrial respiration chain was associated with hydroxyl radical (・OH) generation in rat striatum in carbon monoxide (CO) poisoning by means of brain microdialysis, since CO inhibits the complex IV in the respiratory chain. MPP^+ (complex I inhibitor), malonate (complex II inhibitor) and NaCN (complex IV inhibitor, like CO) stimulated ・OH generation in rat striatum by themselves. CO in combination with MPP^+ or NaCN resulted in the additive potentiation of ・OH generation, while the effect of the combined treatment with CO and malonate was synergistical. NaCN had no such synergistic effect when combined with malonate, suggesting that the synergistic potentiation of ・OH generation by CO and malonate may be derived from CO actions other than the inhibition of the complex IV. On the other hand, the CO-induced ・OH generation was suppressed and potentiated by nitric oxide (NO) synthase (NOS) inhibitors, N^G-nitro-L-arginine methyl ester and N^G-monomethyl-L-arginine, respectively. The effects of these NOS inhibitors were attenuated by the NO precursor, L-arginine, while D-arginine strongly stimulated the CO-induced ・OH generation in the presence of NOS inhibitors. These findings suggest that the CO-induced ・OH generation may be mediated by complex mechanisms. If NO participates in the mechanisms, NOS, but not NO per se, might play a role. Although NO modifies the mitochondiral repiratory chain, it is unclear whether NO plays a role in the synergistic potentiation in ・OH generation by CO and malonate.

与细胞刺激中的氧气相关的线粒体呼吸chath道。一氧化碳（CO）P^+（复合物I抑制剂），Malonate（复合物II抑制剂）和NaCN（复合物）IV抑制剂（例如CO）CO的纹状体与MPP^+或NaCN结合同时，与Malonate的合并治疗是协同的。并通过一氧化氮（NO）抑制剂，nibitor，Nitro-L-精氨酸甲基增强。如果没有参与您的机制，则可以通过CO和MALONATE的OH生成来介导NOS抑制剂。

项目成果

期刊论文数量（2）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Nittric oxide-independent cGMP efflux in the striatum of rats exposed to carbon monoxide, as determined by microdialysis

通过微透析测定暴露于一氧化碳的大鼠纹状体中不依赖一氧化氮的 cGMP 流出

DOI：
发表时间：
2007
期刊：
Journal of Pharmacological Sciences (印刷中)
影响因子：
0
作者：
Takeshi Saito;Hiroyasu Mase;Sanae Takeichi;Sadaki Inokuchi.;Ayako Kuriki;Hara S.et al.
通讯作者：
Hara S.et al.

Nitric oxide-independent cGMP efflux in the striatum of rats exposed to carbon monoxide, as determined by microdialysis

通过微透析测定暴露于一氧化碳的大鼠纹状体中不依赖一氧化氮的 cGMP 流出