Inactivation of bad by site-specific phosphorylation: the checkpoint for ischemic astrocytes to initiate or resist apoptosis.
Bcl-2-associated death protein (Bad), a member of the Bcl family, directs astrocytes in primary cultures to enter or resist apoptosis during ischemia in vitro. Under ischemia, Bad was the only Bcl family member whose expression was upregulated significantly during the early stages of an ischemic insult. Increased endogenous Bad was translocated from the cytoplasm to mitochondria to induce apoptosis in astrocytes. Concurrently, ischemia also induced Bad phosphorylation specifically on Ser112 to promote survival. This site-specific phosphorylation of Bad was mediated by an early activation of the mitogen-activated protein kinase/extracellular signal-regulated protein kinase (MAPK/ERK) intracellular signaling pathway. This study demonstrates that ischemia-induced Bad plays a dual role in determining whether astrocytes enter or resist apoptosis after an ischemic insult.
Chen
Xiao Qian
XQ
Neuroscience Research Institute, Peking University, Beijing, China.
Lau
Lok Ting
LT
Fung
Yin-Wan Wendy
YW
Yu
Albert Cheung Hoi
AC
D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D001253:Astrocytes / Q000502:physiology*; D015153:Blotting, Western / Q000379:methods; D002352:Carrier Proteins / Q000378:metabolism*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology*; D045304:Cytochromes c / Q000378:metabolism; D004790:Enzyme Induction / Q000502:physiology; D005456:Fluorescent Dyes / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D007150:Immunohistochemistry / Q000379:methods; D047468:Immunoprecipitation / Q000379:methods; D020287:In Situ Nick-End Labeling / Q000379:methods; D007511:Ischemia / Q000378:metabolism*; D051379:Mice; D008813:Mice, Inbred ICR; D008928:Mitochondria / Q000378:metabolism; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D008954:Models, Biological; D016297:Mutagenesis, Site-Directed / Q000502:physiology*; D009474:Neurons / Q000187:drug effects; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D013997:Time Factors; D014162:Transfection / Q000379:methods; D051025:bcl-Associated Death Protein
C494820:Bad protein, mouse; D002352:Carrier Proteins; D005456:Fluorescent Dyes; D051025:bcl-Associated Death Protein; D049452:Green Fluorescent Proteins; D045304:Cytochromes c; D019869:Phosphatidylinositol 3-Kinases; D020929:Mitogen-Activated Protein Kinase Kinases