Lithium blocks ethanol-induced modulation of protein kinases in the developing brain

被引：36

作者：

Chakraborty, Goutam ^{[1
,4
]}

Saito, Mitsuo ^{[2
,3
]}

Mao, Rui-Fen ^{[1
]}

Wang, Ray ^{[1
]}

Vadasz, Csaba ^{[1
,3
]}

Saito, Mariko ^{[1
,3
]}

机构：

[1] Nathan S Kline Inst Psychiat Res, Lab Neurobehav Genet, 140 Old Orangeburg Rd, Orangeburg, NY 10962 USA

[2] Nathan S Kline Inst Psychiat Res, Div Analyt Psychopharmacol, Orangeburg, NY 10962 USA

[3] NYU Med Ctr, Dept Psychiat, New York, NY 10016 USA

[4] Montclair State Univ, Dept Chem & Biochem, Montclair, NJ 07043 USA

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2008年 / 367卷 / 03期

关键词：

lithium; ethanol; brain; apoptosis; caspase-3; Akt; glycogen synthase kinase-3 beta; AMP-activated protein kinase;

D O I：

10.1016/j.bbrc.2008.01.004

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 [生物化学与分子生物学]; 081704 [应用化学];

摘要：

Lithium has been shown to be neuroprotective against various insults including ethanol exposure. We previously reported that ethanol-induced apoptotic neurodegencration in the postnatal day 7 (P7) mice is associated with decreases in phosphorylation levels of Akt, glycogen synthase kinase-3 beta (GSK-3 beta), and AMP-activated protein kinase (AMPK), and alteration in lipid profiles in the brain. Here, P7 mice were injected with ethanol and lithium, and the effects of lithium on ethanol-induced alterations in phosphorylation levels of protein kinases and lipid profiles in the brain were examined. Immunoblot and immunohistochemical analyses showed that lithium significantly blocked ethanol-induced caspase-3 activation and reduction in phosphorylation levels of Akt, GSK-3 beta, and AMPK. Further, lithium inhibited accumulation of cholesterol ester (ChE) and N-acylphosphatidylethanolamine (NAPE) triggered by ethanol in the brain. These results suggest that Akt, GSK-3 beta, and AMPK are involved in ethanol-induced neurodegeneration and the neuroprotective effects of lithium by modulating both apoptotic and survival pathways. (C) 2008 Elsevier Inc. All rights reserved.

引用

页码：597 / 602

页数：6

共 37 条

[1]

Ethanol promotes apoptosis in cerebellar granule cells by inhibiting the trophic effect of NMDA [J].