alphaB-crystallin suppresses oxidative stress-induced astrocyte apoptosis by inhibiting caspase-3 activation.

Abstract

alphaB-crystallin is a member of the small heat shock proteins, which is abundantly expressed in various vertebrate tissues including the central nervous system. In our previous report, we showed alphaB-crystallin induction in activated astrocytes in the postischemic brain and in H2O2-treated primary astrocyte cultures. To investigate the functional significance of alphaB-crystallin induction in astrocytes, we generated a stable C6 astroglioma cell line overexpressing alphaB-crystallin. In these cells, hydrogen peroxide-induced apoptosis was reduced by 60% compared to parent cells. Furthermore, the repression of alphaB-crystallin expression by alphaB-crystallin siRNA transfection suppressed this protective effect, indicating that alphaB-crystallin is responsible for the protection against H2O2-induced apoptosis in C6 astroglioma cells. Similar level of aggravation in H2O2-induced apoptosis was observed in primary astrocyte cultures when alphaB-crystallin expression was suppressed by alphaB-crystallin siRNA transfection, confirming the importance of alphaB-crystallin. In addition, the induction of caspase-3 activity after H2O2 treatment was markedly suppressed in alphaB-crystallin-overexpressing cells, and immunoprecipitation proved binding between alphaB-crystallin and partially processed caspase-3 (a p24 intermediate). These results indicate that alphaB-crystallin confers protection against hydrogen peroxide-induced astrocytes apoptosis in part by inhibiting caspase-3 activation.

• Authors: Joo-Hyun Shin, Seung-Woo Kim, Chae-Moon Lim, Ji-Young Jeong, Chun-Shu Piao, Ja-Kyeong Lee
• Journal: Neuroscience research (Neurosci Res) Vol. 64 Issue 4 Pg. 355-61 (Aug 2009) ISSN: 1872-8111 [Electronic] Ireland
• PMID: 19379782 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Oxidants
• alpha-Crystallin B Chain
• Hydrogen Peroxide
• Caspase 3

Topics

• Animals
• Apoptosis (drug effects, physiology)
• Astrocytes (drug effects, metabolism)
• Caspase 3 (metabolism)
• Cell Line, Tumor
• Cytoprotection (physiology)
• Down-Regulation (physiology)
• Hydrogen Peroxide (toxicity)
• Neurodegenerative Diseases (genetics, metabolism, physiopathology)
• Oxidants (toxicity)
• Oxidative Stress (drug effects, physiology)
• Protein Binding (physiology)
• RNA Interference (physiology)
• Rats
• Transfection
• alpha-Crystallin B Chain (genetics, metabolism)