Nitric oxide-induced apoptosis in cultured rat astrocytes: Protection by edaravone, a radical scavenger
Nitric oxide-induced apoptosis in cultured rat astrocytes: Protection by edaravone, a radical scavenger
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DOI：
10.1002/glia.20541
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发表时间：
2007-10-01
期刊：
影响因子：
6.2
通讯作者：
Matsuda, Toshio
中科院分区：
文献类型：
--
作者：
Kawasaki, Toshiyuki;Kitao, Tatsuya;Matsuda, Toshio
一氧化氮诱导培养的星形胶质细胞凋亡样细胞死亡，但确切机制尚不清楚。本研究进一步探讨了一氧化氮诱导细胞毒性的机制，并检测了自由基清除剂依达拉奉对细胞毒性的影响。用一氧化氮供体硝普钠(SNP)处理培养的大鼠星形胶质细胞72h，可导致细胞死亡，从而降低细胞存活率。损伤伴随着活性氧的产生和核凋亡诱导因子水平的增加，但caspase活性没有变化。SNP诱导的细胞毒作用可被c-jun氨基末端蛋白激酶(JNK)抑制剂SP600125(20mU M)、p38丝裂原活化蛋白(MAP)激酶抑制剂SB203580(20mU M)和细胞外信号调节蛋白(ERK)抑制剂U0126(10mU M)阻断，一氧化氮供体可刺激p38 MAP、JNK和ERK的磷酸化。依达拉奉(10 MU M)对SNP诱导的星形胶质细胞损伤有保护作用，并可抑制SNP诱导的p38 MAP、JNK和ERK的磷酸化及活性氧的产生。依达拉奉还可减弱SNP诱导的核凋亡诱导因子水平的升高。这些结果表明，MAP激酶通路在一氧化氮诱导的星形胶质细胞凋亡中起关键作用，依达拉奉通过抑制NO诱导的星形胶质细胞MAP激酶的激活来保护其免受NO诱导的细胞毒性。(C)2007年Wiley-Liss，Inc.
Nitric oxide induces apoptosis-like cell death in cultured astrocytes, but the exact mechanism is not known. This study further characterized the mechanism of nitric oxide-induced cytotoxicity, and examined the effect of edaravone, a radical scavenger, on cytotoxicity. Treatment of cultured rat astrocytes with sodium nitroprusside (SNP), a nitric oxide donor, for 72 h, decreased cell viability by causing apoptosis-like cell death. The injury was accompanied by increases in the production of reactive oxygen species and in the level of nuclear apoptosis-inducing factor, but not in caspase activity. SNP-induced cytotoxicity was blocked by the c-jun N-terminal protein kinase (JNK) inhibitor SP600125 (20 mu M), the p38 mitogen-activated protein (MAP) kinase inhibitor SB203580 (20 mu M), and the extracellular signal-regulating kinase (ERK) inhibitor U0126 (10 mu M), and the nitric oxide donor stimulated the phosphorylation of p38 MAP kinase, JNK, and ERK. Edaravone (10 mu M) protected astrocytes against SNP-induced cell injury and it inhibited SNP-induced phosphorylation of p38 MAP kinase, JNK, and ERK, and the production of reactive oxygen species. Edaravone also attenuated SNP-induced increase in nuclear apoptosis-inducing factor levels. These results suggest that MAP kinase pathways play a key role in nitric oxide-induced apoptosis and that edaravone protects against nitric oxide-induced cytotoxicity by inhibiting nitric oxide-induced MAP kinase activation in astrocytes. (c) 2007 Wiley-Liss, Inc.