丝裂原活化蛋白激酶（MAPKs）介导大鼠原代星形胶质细胞中SIN-1/葡萄糖剥夺诱导的死亡。

Mitogen-activated protein kinases (MAPKs) mediate SIN-1/ glucose deprivation-induced death in rat primary astrocytes.

作者信息

Yoo oung Kwon, Choi Ji Woong, Choi Min Sik, Ryu Mi Kyoung, Park Gyu Hwan, Jeon Mi Jin, Ko Kwang Ho

机构信息

Department of Pharmacology, College of Pharmacy, Seoul National University, San 56-1, Shinlim-Dong, Kwanak-Gu, Seoul 151-742, Korea.

出版信息

Arch Pharm Res. 2005 Aug;28(8):942-7. doi: 10.1007/BF02973881.

DOI:10.1007/BF02973881

PMID:16178421

Abstract

Peroxynitrite is a potent neurotoxic molecule produced from a reaction between NO and superoxide and induces NO-mediated inflammation under neuropathological conditions. Previously, we reported that glucose deprivation induced ATP depletion and cell death in immunostimulated astrocytes, which was mainly due to peroxynitrite. In this study, the role of MAPKs (ERK1/2, p38MAPK, and JNK1SAPK) signal pathway in the SIN-1/glucose deprivation-induced death of astrocytes was examined. A combined treatment with glucose deprivation and 50 microM SIN-1, an endogenous peroxynitrite generator, rapidly and markedly increased the death in rat primary astrocytes. Also, SIN-1/glucose deprivation resulted in the activation of MAPKs, which was significantly blocked by the treatment with 20 microM MAPKs inhibitors (ERK1/2, PD98059; p38MAPK, SB203580; JNK/SAPK, SP600125). Interestingly, SIN-1/glucose deprivation caused the loss of intracellular ATP level, which was significantly reversed by MAPKs inhibitors. These results suggest that the activation of MAPKs plays an important role in SIN-1/glucose deprivation-induced cell death by regulating the intracellular ATP level.

摘要

过氧亚硝酸盐是一种由一氧化氮（NO）和超氧化物反应产生的强效神经毒性分子，在神经病理条件下可诱导NO介导的炎症反应。此前，我们报道过免疫刺激的星形胶质细胞中葡萄糖剥夺会导致ATP耗竭和细胞死亡，这主要归因于过氧亚硝酸盐。在本研究中，我们检测了丝裂原活化蛋白激酶（MAPKs，包括ERK1/2、p38MAPK和JNK1/SAPK）信号通路在SIN-1/葡萄糖剥夺诱导的星形胶质细胞死亡中的作用。葡萄糖剥夺与50微摩尔SIN-1（一种内源性过氧亚硝酸盐生成剂）联合处理能迅速且显著增加大鼠原代星形胶质细胞的死亡。此外，SIN-1/葡萄糖剥夺导致MAPKs活化，而用20微摩尔MAPKs抑制剂（ERK1/2，PD98059；p38MAPK，SB203580；JNK/SAPK，SP600125）处理可显著阻断这种活化。有趣的是，SIN-1/葡萄糖剥夺导致细胞内ATP水平降低，而MAPKs抑制剂可显著逆转这一现象。这些结果表明，MAPKs的活化通过调节细胞内ATP水平在SIN-1/葡萄糖剥夺诱导的细胞死亡中起重要作用。