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Angiotensin II attenuates chemical hypoxia-induced caspase-3 activation in primary cortical neuronal cultures.

Authors
  • Grammatopoulos, Tom N
  • Morris, Katherine
  • Bachar, Cheryl
  • Moore, Steve
  • Andres, Robert
  • Weyhenmeyer, James A
Type
Published Article
Journal
Brain Research Bulletin
Publisher
Elsevier
Publication Date
Jan 15, 2004
Volume
62
Issue
4
Pages
297–303
Identifiers
PMID: 14709344
Source
Medline
License
Unknown

Abstract

In this study we determined whether caspase-3 is required in mouse cortical neurons for sodium azide-mediated apoptosis. Primary cortical neuronal cultures were treated with a cell permeable caspase-3 inhibitor, DEVD (1 nM-100 fM), prior to sodium azide-induced hypoxia. Treatment with the caspase-3 inhibitor resulted in a dose-dependent decrease in apoptosis, suggesting that sodium azide-induced apoptosis is mediated through a caspase-3 dependent pathway. Levels of cytochrome-c release and caspase-3 cleavage were assayed by Western analysis. Cytochrome-c release and caspase-3 cleavage were observed at 5 h (85.3+/-5.8%) and 8 h (53.4+/-14.9%), respectively. We have previously reported that angiotensin II, acting through the AT(2) receptor subtype, protects cultured mouse cortical neurons from sodium azide-induced apoptosis. We also examined whether the protective effect of angiotensin II is mediated through modulation of caspase-3. Pre-treatment of cells with angiotensin II and the AT(1) receptor antagonist, losartan, reduced levels of sodium azide-induced caspase-3 cleavage by 95.0+/-4.0%. Cells pre-treated with the AT(2) receptor antagonist, PD123319 showed a smaller reduction of caspase-3 cleavage (53.8+/-3.4%). Our findings indicate that sodium azide-induced apoptosis is caspase-3 dependent and that angiotensin II protects cortical neurons from chemical-induced apoptosis by reducing caspase-3 cleavage.

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