title: Akt attenuates apoptotic death through phosphorylation of H2A under hydrogen peroxide-induced oxidative stress in PC12 cells and hippocampal neurons.
abstract: Although the essential role of protein kinase B (PKB)/Akt in cell survival signaling has been clearly established, the mechanism by which Akt mediates the cellular response to hydrogen peroxide (H2O2)-induced oxidative stress remains unclear. We demonstrated that Akt attenuated neuronal apoptosis through direct association with histone 2A (H2A) and phosphorylation of H2A at threonine 17. At early time points during H2O2 exposure of PC12 cells and primary hippocampal neurons, when the cells can tolerate the level of DNA damage, Akt was activated and phosphorylated H2A, leading to inhibition of apoptotic death. At later time points, Akt delivered the NAD(+)-dependent protein deacetylase Sirtuin 2 (Sirt 2) to the vicinity of phosphorylated H2A in response to irreversible DNA damage, thereby inducing H2A deacetylation and subsequently leading to apoptotic death. Ectopically expressed T17A-substituted H2A minimally interacted with Akt and failed to prevent apoptosis under oxidative stress. Thus Akt-mediated H2A phosphorylation has an anti-apoptotic function in conditions of H2O2-induced oxidative stress in neurons and PC12 cells.
authors.affiliation: Department of Molecular Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon 440-746, Korea.|Center for Molecular Medicine, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon 440-746, Korea.
authors.forename: Ji Hye
authors.initials: JH
authors.lastname: Park
authors.affiliation: Department of Molecular Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon 440-746, Korea.|Center for Molecular Medicine, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon 440-746, Korea.
authors.forename: Chung Kwon
authors.initials: CK
authors.lastname: Kim
authors.affiliation: Department of Molecular Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon 440-746, Korea.
authors.forename: Sang Bae
authors.initials: SB
authors.lastname: Lee
authors.affiliation: Department of Anatomy and Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon 440-746, Korea.|Center for Molecular Medicine, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon 440-746, Korea.
authors.forename: Kyung-Hoon
authors.initials: KH
authors.lastname: Lee
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Ulsan, College of Medicine, Seoul 138-736, Korea.
authors.forename: Sung-Woo
authors.initials: SW
authors.lastname: Cho
authors.affiliation: Department of Molecular Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon 440-746, Korea.|Center for Molecular Medicine, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon 440-746, Korea.
authors.forename: Jee-Yin
authors.initials: JY
authors.lastname: Ahn
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D004249:DNA Damage; D005786:Gene Expression Regulation; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006657:Histones / Q000235:genetics* / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018384:Oxidative Stress; D016716:PC12 Cells; D010766:Phosphorylation / Q000187:drug effects; D061251:Primary Cell Culture; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction; D056565:Sirtuin 2 / Q000235:genetics / Q000378:metabolism; D013912:Threonine / Q000378:metabolism*
chemical_list: D006657:Histones; C097475:Sirt2 protein, rat; D013912:Threonine; D006861:Hydrogen Peroxide; D051057:Proto-Oncogene Proteins c-akt; D056565:Sirtuin 2