title: p38β MAPK affords cytoprotection against oxidative stress-induced astrocyte apoptosis via induction of αB-crystallin and its anti-apoptotic function.
abstract: The activation of p38 mitogen-activated protein kinases (MAPKs) has been implicated in many cellular processes, such as, inflammation, cell death, and survival. In mammals, four distinct genes encode the four known members of p38 MAPKs, p38α, p38β, p38γ, and p38δ. Despite the fact that p38α and p38β MAPKs share over 75% homology sequences, they have distinct, perhaps even opposite roles under stress conditions. In our previous report, we showed that p38β MAPK is induced in activated astrocytes in the penumbra of the postischemic brain, wherein it was co-localized with αB-crystallin and MAPKAPK-2. To investigate the functional significance of p38β MAPK in astrocytes, a C6 astroglioma cell line stably over-expressing p38β MAPK was generated. In these cells, hydrogen peroxide-induced apoptosis was reduced to 44.3% of that obtained from normal C6 cells. Interestingly, we found that expression of a small heat shock protein, αB-crystallin, was significantly increased in these cells, but that the expressions of HSP27 and HSP70 were not. Repression of αB-crystallin expression by αB-crystallin siRNA transfection suppressed the protective effect and recovered caspase 3 activity, indicating that αB-crystallin induction plays a crucial role in the protection against H₂O₂-induced apoptosis observed in p38β-overexpressing C6 astroglioma cells. We found that the binding between αB-crystallin and partially processed caspase-3 (a p24 intermediate) was significantly increased in p38β-overexpressing cells, which might result in suppression of caspase 3 activity in these cells. These results indicate that p38β confers protection against H₂O₂-induced astrocytes apoptosis by inducing a small heat shock protein, αB-crystallin, which inhibits caspase-3 activation.
authors.affiliation: Department of Anatomy and Center for Advanced Medical Education (BK21 Project), Inha University School of Medicine, 7-241 Shinheung-dong, Jung-Gu, Inchon 400-712, Republic of Korea.
authors.forename: Joo-Hyun
authors.initials: JH
authors.lastname: Shin
authors.forename: Ji-Young
authors.initials: JY
authors.lastname: Jeong
authors.forename: Yinchuan
authors.initials: Y
authors.lastname: Jin
authors.forename: Il-Doo
authors.initials: ID
authors.lastname: Kim
authors.forename: Ja-Kyeong
authors.initials: JK
authors.lastname: Lee
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis / Q000502:physiology; D001253:Astrocytes / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D001254:Astrocytoma / Q000201:enzymology / Q000378:metabolism / Q000517:prevention & control; D053148:Caspase 3; D061945:Caspase Inhibitors; D045744:Cell Line, Tumor; D019610:Cytoprotection / Q000502:physiology*; D006360:Heat-Shock Proteins / Q000096:biosynthesis* / Q000502:physiology; D048290:Mitogen-Activated Protein Kinase 11 / Q000502:physiology*; D018384:Oxidative Stress / Q000502:physiology*; D051381:Rats; D038203:alpha-Crystallin B Chain / Q000096:biosynthesis* / Q000502:physiology
chemical_list: D051017:Apoptosis Regulatory Proteins; D061945:Caspase Inhibitors; D006360:Heat-Shock Proteins; D038203:alpha-Crystallin B Chain; D048290:Mitogen-Activated Protein Kinase 11; C505410:Casp3 protein, rat; D053148:Caspase 3