title: Interplay between histone acetylation/deacetylation and poly(ADP-ribosyl)ation in the development of ischemic tolerance in vitro.
abstract: Ischemic tolerance is an endogenous defense program in which exposure to a subtoxic preconditioning insult results in resistance to a subsequent, otherwise lethal, episode of ischemia. Herein, we evaluated the role of histone acetylation/deacetylation in an in vitro model of preconditioning, using rat organotypic hippocampal slices exposed to 30 min oxygen-glucose deprivation (OGD), which leads to CA1 injury 24 h later: tolerance was induced by exposing the slices to preconditioning bouts of NMDA (3 μM for 60 min) 24 h prior to the toxic OGD challenge. Under these conditions, CA1 damage induced by OGD was reduced. The induction of tolerance was prevented by incubating the slices with HDAC inhibitors. NMDA preconditioning was associated with a mild increase in poly(ADP-ribose) polymerase (PARP) activity that was apparently followed, 3 h later, by a mild increase in histone acetylation. Use of PARP and HDAC inhibitors suggests a possible interaction between PARP and HDAC activities in the development of ischemic tolerance. Finally, both PARP and HDAC inhibitors were able to prevent the increase in pERK1/2 induced by NMDA preconditioning. We propose a model in which mild histone acetylation and PARP activity cooperate in producing a neuroprotective response in the development of ischemic tolerance.
authors.affiliation: Department of Health Sciences, Section of Clinical Pharmacology and Oncology, University of Florence, Viale G. Pieraccini 6, 50139 Florence, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Gerace
authors.affiliation: Department of Health Sciences, Section of Clinical Pharmacology and Oncology, University of Florence, Viale G. Pieraccini 6, 50139 Florence, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Landucci
authors.affiliation: Department of Health Sciences, Section of Clinical Pharmacology and Oncology, University of Florence, Viale G. Pieraccini 6, 50139 Florence, Italy.
authors.forename: Tania
authors.initials: T
authors.lastname: Scartabelli
authors.affiliation: Department of Neuroscience, Psychology, Drug Research and Child Health (NeuroFarBa), Section of Pharmacology and Toxicology, University of Florence, Viale G. Pieraccini 6, 50139 Florence, Italy.
authors.forename: Flavio
authors.initials: F
authors.lastname: Moroni
authors.affiliation: Department of Health Sciences, Section of Clinical Pharmacology and Oncology, University of Florence, Viale G. Pieraccini 6, 50139 Florence, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Chiarugi
authors.affiliation: Department of Health Sciences, Section of Clinical Pharmacology and Oncology, University of Florence, Viale G. Pieraccini 6, 50139 Florence, Italy.
authors.forename: Domenico E
authors.initials: DE
authors.lastname: Pellegrini-Giampietro
mesh_terms: D000107:Acetylation / Q000187:drug effects; D000818:Animals; D000831:Animals, Newborn; D020148:Butyric Acid / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000502:physiology; D005947:Glucose / Q000172:deficiency*; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism*; D006657:Histones / Q000378:metabolism*; D006877:Hydroxamic Acids / Q000494:pharmacology; D000860:Hypoxia; D066298:In Vitro Techniques; D016202:N-Methylaspartate / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D009924:Organ Culture Techniques; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D000077337:Vorinostat
chemical_list: D004791:Enzyme Inhibitors; D006657:Histones; D006877:Hydroxamic Acids; D020148:Butyric Acid; D000077337:Vorinostat; D016202:N-Methylaspartate; D011065:Poly(ADP-ribose) Polymerases; D005947:Glucose
keywords: HDAC inhibitors; Histone acetylation/deacetylation; Ischemia tolerance; NMDA; Poly(ADPribosyl)ation; Preconditioning