title: In vitro ischemia decreases histone H4K16 acetylation in neural cells.
abstract: Inhibitors of histone deacetylases are frequently used against ischemia-induced injury, but the specific mechanisms of their action are poorly understood. Here, we report that following a 5-7-h oxygen-glucose deprivation (OGD) acetylation of histone H4 at residue K16 (H4K16Ac) decreases by 40-80% in both PC12 cells and primary neurons. This effect can be reverted by treatment with trichostatin A, or by supplementation with acetyl-CoA. A decrease in H4K16Ac levels can affect the expression of mitochondrial uncoupling protein 2 (UCP2), huntingtin-interacting protein 1 (HIP1) and Notch-pathway genes in a cell-specific manner. Thus, H4K16 acetylation is important for responses to ischemia and cell energy stress, and depends on both cytosolic and mitochondrial acetyl-CoA.
authors.affiliation: School of Biochemistry and Cell Biology, University College Cork, Cork, Ireland. Electronic address: r.dmitriev@ucc.ie.
authors.forename: Ruslan I
authors.initials: RI
authors.lastname: Dmitriev
authors.affiliation: School of Biochemistry and Cell Biology, University College Cork, Cork, Ireland.
authors.forename: Dmitri B
authors.initials: DB
authors.lastname: Papkovsky
mesh_terms: D000105:Acetyl Coenzyme A / Q000235:genetics / Q000378:metabolism; D000107:Acetylation; D000818:Animals; D015687:Cell Hypoxia / Q000502:physiology; D004734:Energy Metabolism / Q000502:physiology; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D007473:Ion Channels / Q000235:genetics / Q000378:metabolism; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D016716:PC12 Cells; D051381:Rats; D051880:Receptors, Notch / Q000235:genetics / Q000378:metabolism; D000071246:Uncoupling Protein 2
chemical_list: D006657:Histones; D007473:Ion Channels; D024101:Mitochondrial Proteins; D051880:Receptors, Notch; C000604391:Ucp2 protein, rat; D000071246:Uncoupling Protein 2; D000105:Acetyl Coenzyme A
keywords: H4K16; Histone (de)acetylation; Histone acetyltransferase; Hypoxia; Ischemic tolerance; Oxygen and glucose deprivation