Glycogen synthase kinase-3β facilitates staurosporine- and heat shock-induced apoptosis -: Protection by lithium
Glycogen synthase kinase-3β facilitates staurosporine- and heat shock-induced apoptosis -: Protection by lithium
复制标题
DOI：
10.1074/jbc.275.11.7583
复制
发表时间：
2000-03-17
影响因子：
4.8
通讯作者：
Jope, RS
中科院分区：
文献类型：
--
作者：
Bijur, GN;De Sarno, P;Jope, RS
在人SH-SY 5 Y神经母细胞瘤细胞中检查糖原合成酶激酶-3 β在调节细胞凋亡中的潜在作用。星形孢菌素治疗引起caspase-3和caspase-9的活性的时间和浓度依赖性增加，但不是caspase-1，增加聚（ADP-核糖）聚合酶的蛋白水解，并诱导与细胞凋亡一致的形态学变化。糖原合成酶激酶-3 β过表达至对照细胞水平的3.5倍，并没有改变凋亡的基础指数，但加强了星形孢菌素诱导的caspase-3、caspase-9的活化，多聚腺苷酸的蛋白水解，（ADP-核糖）聚合酶和指示凋亡的形态学变化，锂抑制糖原合成酶激酶-3 β可减弱星形孢菌素诱导的caspase-3激活。3在过表达糖原合成酶激酶-3 β的细胞中。在热休克的细胞中，半胱天冬酶-3的活性在糖原合成酶激酶-3 β转染的细胞中比对照细胞大三倍以上，并且这种增强的反应被锂处理抑制。因此，糖原合成酶激酶-3 β促进由两种实验范例诱导的细胞凋亡。这些发现表明，糖原合成酶激酶-3 β可能有助于促凋亡信号传导活性，抑制糖原合成酶激酶-3 β可能有助于抗凋亡信号传导机制，锂的神经保护作用可能部分归因于其对糖原合成酶激酶-3 β的抑制性调节。
The potential role of glycogen synthase kinase-3 beta in modulating apoptosis was examined in human SH-SY5Y neuroblastoma cells. Staurosporine treatment caused time- and concentration-dependent increases in the activities of caspase-3 and caspase-9 but not caspase-1, increased proteolysis of poly(ADP-ribose) polymerase, and induced morphological changes consistent with apoptosis. Overexpression of glycogen synthase kinase-3 beta to levels 3.5 times that in control cells did not alter basal indices of apoptosis but potentiated staurosporine-induced activation of caspase-3, caspase-9, proteolysis of poly(ADP-ribose) polymerase, and morphological changes indicative of apoptosis, Inhibition of glycogen synthase kinase-3 beta by lithium attenuated the enhanced staurosporine-induced activation of caspase-3 in cells overexpressing glycogen synthase kinase-3 beta. In cells subjected to heat shock, caspase-3 activity was more than three times greater in glycogen synthase kinase-3 beta-transfected than control cells, and this potentiated response was inhibited by lithium treatment. Thus, glycogen synthase kinase-3 beta facilitated apoptosis induced by two experimental paradigms. These findings indicate that glycogen synthase kinase-3 beta may contribute to proapoptotic-signaling activity, that inhibition of glycogen synthase kinase-3 beta can contribute to anti-apoptotic-signaling mechanisms, and that the neuroprotective actions of lithium may be due in part to its inhibitory modulation of glycogen synthase kinase-3 beta.