Akt attenuates apoptotic death through phosphorylation of H2A under hydrogen peroxide-induced oxidative stress in PC12 cells and hippocampal neurons

Scientific Reports
Ji Hye ParkJee-Yin Ahn

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.

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Citations

Dec 15, 2019·Archives of Physiology and Biochemistry·Rachid AkkiAngela Marino
Mar 30, 2017·Frontiers in Molecular Neuroscience·Yan WangJunping Kou
Jul 30, 2019·BioMed Research International·Zhenwei FanPeng Li
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Feb 28, 2021·Neurobiology of Disease·Elva Martin-BatistaTeresa Giraldez
Mar 11, 2021·Free Radical Biology & Medicine·José-Luis García-GiménezFederico V Pallardó
Apr 18, 2021·Biochemical and Biophysical Research Communications·Eika AndoHiroshi Takeuchi

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Methods Mentioned

BETA
immunoprecipitation
pull-down
nuclear translocation
acetylation
immunoprecipitation assay
transfection
transfections

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis