alphaB-crystallin suppresses oxidative stress-induced astrocyte apoptosis by inhibiting caspase-3 activation.
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.
Shin
Joo-Hyun
JH
Department of Anatomy, Inha University School of Medicine, Inchon, Republic of Korea.
Kim
Seung-Woo
SW
Lim
Chae-Moon
CM
Jeong
Ji-Young
JY
Piao
Chun-Shu
CS
Lee
Ja-Kyeong
JK
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D053148:Caspase 3 / Q000378:metabolism*; D045744:Cell Line, Tumor; D019610:Cytoprotection / Q000502:physiology; D015536:Down-Regulation / Q000502:physiology; D006861:Hydrogen Peroxide / Q000633:toxicity; D019636:Neurodegenerative Diseases / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D016877:Oxidants / Q000633:toxicity; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D011485:Protein Binding / Q000502:physiology; D034622:RNA Interference / Q000502:physiology; D051381:Rats; D014162:Transfection; D038203:alpha-Crystallin B Chain / Q000235:genetics* / Q000378:metabolism*
D016877:Oxidants; D038203:alpha-Crystallin B Chain; D006861:Hydrogen Peroxide; D053148:Caspase 3