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Dual effect of nitric oxide on cell death : Induction and protection of apoptosis

一氧化氮对细胞死亡的双重作用：诱导和保护细胞凋亡

基本信息

批准号：
13672314
负责人：
MAEDA Sadaaki
金额：
$ 0.45万
依托单位：
Setsunan University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2002
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13672314/
关键词：
nitric oxide apoptosis cyclic GMP cytochrome c RAW 264 cells protein kinase G Bax 一酸化炭素 Cyclic GMP Protein kinase G

项目摘要

We investigated the protective effect of nitric oxide (NO) at a low concentration on cell death induced by NO and its mechanism in human neuroblastoma SH-SY5Y cells and mouse macrophage cell line, RAW264.Sodium nitroprusside (SNP), an NO donor, induced cell death in SH-SY5Y cells. Pretreatment with NOC12, an NO donor, at a low concentration partially prevented the cell death induced by SNP. Pretreatment with cyclic GMP analogues, dibutyryl-cGMP, prevented SNP-induced cell death. NOC12 at a low concentration, which has no effect on the cell viability, induced cell death in the presence of a guanylate cyclase inhibitor, LY83583. The cell death was partially protected by dibutyryl-cGMP. These results suggest that cGMP has a protective effect on NO-induced cell death in SH-SY5Y cells.Pretreatment with 100 μM SNP for 24h prevented the cell death and cytochrome c release induced by 4 mM SNP in RAW264 cells. The effect of SNP pretreatment was reduced by LY83583 (guanylyl cyclase inhibitors). Pretreatment with DBcGMP prevented cell death induced by NOC18, GSNO or SNP, in a concentration- dependent manner. Pretreatment with DBcGMP prevented cytochrome c release induced by NO donors. The protective effect of SNP or DBcGMP was significantly attenuated by KT5823 (a protein kinase G inhibitor). These results indicate that NO at a low concentration protects RAW264 cells from the cytotoxicity of NO through cGMP production and activation of PKG.

研究了低浓度一氧化氮（NO）对人神经母细胞瘤SH-SY5Y细胞和小鼠巨噬细胞RAW264细胞凋亡的保护作用及其机制。硝普钠（SNP）作为NO供体，诱导SH-SY5Y细胞死亡。低浓度no12预处理能部分抑制SNP诱导的细胞死亡。用环GMP类似物二丁基cgmp预处理，可防止snp诱导的细胞死亡。在鸟苷酸环化酶抑制剂LY83583存在的情况下，低浓度的no12诱导细胞死亡，对细胞活力没有影响。二丁基- cgmp对细胞死亡有部分保护作用。提示cGMP对no诱导的SH-SY5Y细胞死亡具有保护作用。100 μM SNP预处理24h可抑制4 mM SNP诱导的RAW264细胞死亡和细胞色素c释放。LY83583（鸟苷环化酶抑制剂）降低了SNP预处理的效果。DBcGMP预处理对no18、GSNO或SNP诱导的细胞死亡具有浓度依赖性。DBcGMP预处理可抑制NO供体诱导的细胞色素c释放。KT5823（一种蛋白激酶G抑制剂）显著减弱SNP或DBcGMP的保护作用。这些结果表明，低浓度NO通过产生cGMP和激活PKG来保护RAW264细胞免受NO的细胞毒性。