title: Calcineurin-mediated BAD Ser155 dephosphorylation in ammonia-induced apoptosis of cultured rat hippocampal neurons.
abstract: We previously reported that ammonia induced apoptosis in cultured rat hippocampal neurons with moderate increases in the intracellular calcium concentration and decreases in phospho-BAD levels. Since this suggested the involvement of calcineurin in the apoptosis, the effects of calcineurin inhibitors, 1 microM cyclosporin A and 1 microM FK506, on the ammonia-induced neuronal apoptosis were tested. Both of the inhibitors abolished the neuronal apoptosis assessed by double staining with Hoechst 33258 and anti-neurofilament antibody, and the ammonia-induced decrease in phospho-BAD Ser(155) level. Thus, calcineurin appeared to be involved in the dephosphorylation of BAD at the sites including Ser(155) in ammonia-induced apoptosis.
authors.affiliation: Department of Pharmacology, Kansai Medical University, 10-15 Fumizono-cho, Moriguchi, Osaka 570-8506, Japan.
authors.forename: Li
authors.initials: L
authors.lastname: Yang
authors.forename: Kyoko
authors.initials: K
authors.lastname: Omori
authors.forename: Junko
authors.initials: J
authors.lastname: Suzukawa
authors.forename: Chiyoko
authors.initials: C
authors.lastname: Inagaki
mesh_terms: D000641:Ammonia / Q000633:toxicity*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D019703:Calcineurin / Q000378:metabolism*; D065095:Calcineurin Inhibitors; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D002352:Carrier Proteins / Q000378:metabolism*; D002478:Cells, Cultured; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology; D009410:Nerve Degeneration / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology; D016900:Neurofilament Proteins / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D012694:Serine / Q000378:metabolism; D051025:bcl-Associated Death Protein
chemical_list: C494821:Bad protein, rat; D065095:Calcineurin Inhibitors; D002352:Carrier Proteins; D004791:Enzyme Inhibitors; D016900:Neurofilament Proteins; D051025:bcl-Associated Death Protein; D012694:Serine; D000641:Ammonia; D019703:Calcineurin