T-588 inhibits astrocyte apoptosis via mitogen-activated protein kinase signal pathway.
T-588 inhibits astrocyte apoptosis via mitogen-activated protein kinase signal pathway.
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T-588 通过丝裂原激活蛋白激酶信号通路抑制星形胶质细胞凋亡。
DOI：
10.1016/s0014-2999(00)00334-4
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发表时间：
2000
影响因子：
5
通讯作者：
T. Matsuda
中科院分区：
文献类型：
--
作者：
K. Takuma;T. Fujita;Y. Kimura;M. Tanabe;A. Yamamuro;E. Lee;K. Mori;Y. Koyama;A. Baba;T. Matsuda
研究了认知增强剂(1R)-1-benzo[b]thiophen-5-yl-2-[2-(diethylamino)ethoxy]ethan-1-ol盐酸盐(T-588)对培养的大鼠星形胶质细胞再灌注损伤的影响。1~10μM的T-588可部分保护星形胶质细胞免受无钙介质或过氧化氢的再灌注损伤。神经生长因子(NGF)也有类似的保护作用。加入T-588和NGF对钙再灌注损伤均有完全保护作用。T-588不能刺激星形胶质细胞产生NGF。丝裂原活化蛋白(MAP)/细胞外信号调节蛋白(ERK)激酶抑制剂2‘-氨基-3’-甲氧基黄酮(PD98059)可抑制T-588对包括细胞凋亡在内的钙再灌注损伤的影响，但不能被磷脂酰肌醇3-激酶抑制剂Wortmannin所抑制。PD98059和Wortmannin可抑制NGF的作用。T-588能迅速激活星形胶质细胞ERK的磷酸化，但不影响Akt的磷酸化。提示ERK-MAPK通路在T-588和NGF的保护作用中起一定作用。
The effect of (1R)-1-benzo[b]thiophen-5-yl-2-[2-(diethylamino)ethoxy]ethan-1-ol hydrochloride (T-588), a cognition enhancer, on reperfusion injury was studied in cultured rat astrocytes. T-588 at 1–10 μM partially protected astrocytes against reperfusion injury after exposure to Ca2+-free medium or hydrogen peroxide. Nerve growth factor (NGF) had a similar protective effect. Addition of both T-588 and NGF resulted in complete protection against Ca2+reperfusion injury. T-588 did not stimulate NGF production in astrocytes. The effect of T-588 on Ca2+reperfusion injury including apoptosis was inhibited by the mitogen-activated protein (MAP)/extracellular signal-regulated kinase (ERK) kinase inhibitor 2′-amino-3′-methoxyflavone (PD98059), but not by the phosphoinositide 3-kinase inhibitor wortmannin. The effect of NGF was inhibited by PD98059 and wortmannin. T-588 stimulated rapidly the phosphorylation of ERK, but did not affect that of Akt in astrocytes. These findings suggest that the ERK MAP kinase pathway has a role in the protective effects of T-588 and NGF.
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影响因子：
56.9
作者：
HAN, J;LEE, JD;ULEVITCH, RJ
通讯作者：
ULEVITCH, RJ
TPA 介导的药物诱导细胞凋亡抑制需要细胞外信号调节激酶 (ERK) 活性。
影响因子：
3.1
作者：
Stadheim,TA;Kucera,GL
通讯作者：
Kucera,GL
影响因子：
56.9
作者：
Yujiri, T;Sather, S;Johnson, GL
通讯作者：
Johnson, GL
影响因子：
2
作者：
Valente, Andre;Huang, Kuo-Hua;Engert, Florian
通讯作者：
Engert, Florian