Activation of apoptosis-linked caspase(s) in NMDA-injured brains in neonatal rats

被引：21

作者：

Nath, R ^{[1
]}

Scott, R ^{[1
]}

Nadimpalli, R ^{[1
]}

Gupta, R ^{[1
]}

Wang, KKW ^{[1
]}

机构：

[1] Parke Davis Pharmaceut Res, Dept Neurosci Therapeut, Lab Neurobiochem, Ann Arbor, MI 48105 USA

来源：

NEUROCHEMISTRY INTERNATIONAL | 2000年 / 36卷 / 02期

关键词：

caspase; ICE-like; excitotoxicity; neuronal death; protease inhibitor;

D O I：

10.1016/S0197-0186(99)00112-6

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Unilateral injection of 50 nmol of N-methyl-D-aspartate (NMDA) into the left posterior striatum of 7 day-old rat pups induces massive neuronal loss in the ipsilateral hemisphere in 5 days. In this model of excitotoxicity, the form of neuronal death (necrosis vs apoptosis) has not been clearly addressed. Here we report evidence of DNA laddering in the ipsilateral hemisphere 24 h after the NMDA injection. Activation of apoptosis-linked caspase(s) was also identified, as evidenced by (i) the formation of caspase-produced 120 kDa alpha-spectrin breakdown product (SBDP120) and (ii) increase in hydrolysis of caspase-3 substrate acetyl-DEVD-7-amido-4-methylcoumarin in the homogenate from the ipsilateral hemisphere. Lastly, we note that i.p. injection (100 mg/kg) of a pan caspase inhibitor Z-D-DCB attenuates the levels of SBDP120. Our results suggest the presence of caspase activation in this rat pup model of NMDA toxicity. (C) 2000 Published by Elsevier Science Ltd. All rights reserved.

引用

页码：119 / 126

页数：8

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