title: Acetylation of histones in neocortex and hippocampus of rats exposed to different modes of hypobaric hypoxia: Implications for brain hypoxic injury and tolerance.
abstract: Acetylation of nucleosome histones results in relaxation of DNA and its availability for the transcriptional regulators, and is generally associated with the enhancement of gene expression. Although it is well known that activation of a variety of pro-adaptive genes represents a key event in the development of brain hypoxic/ischemic tolerance, the role of epigenetic mechanisms, in particular histone acetylation, in this process is still unexplored. The aim of the present study was to investigate changes in acetylation of histones in vulnerable brain neurons using original well-standardized model of hypobaric hypoxia and preconditioning-induced tolerance of the brain. Using quantitative immunohistochemistry and Western blot, effects of severe injurious hypobaric hypoxia (SH, 180mm Hg, 3h) and neuroprotective preconditioning mode (three episodes of 360mm Hg for 2h spaced at 24h) on the levels of the acetylated proteins and acetylated H3 Lys24 (H3K24ac) in the neocortex and hippocampus of rats were studied. SH caused global repression of the acetylation processes in the neocortex (layers II-III, V) and hippocampus (CA1, CA3) by 3-24h, and this effect was prevented by the preconditioning. Moreover, hypoxic preconditioning remarkably increased the acetylation of H3K24 in response to SH in the brain areas examined. The preconditioning hypoxia without subsequent SH also stimulated acetylation processes in the neocortex and hippocampus. The moderately enhanced expression of the acetylated proteins in the preconditioned rats was maintained for 24h, whereas acetylation of H3K24 was intense but transient, peaked at 3h. The novel data obtained in the present study indicate that large activation of the acetylation processes, in particular acetylation of histones might be essential for the development of brain hypoxic tolerance.
authors.affiliation: Laboratory of Regulation of Brain Neuron Functions, Pavlov Institute of Physiology, Russian Academy of Sciences, Makarova nab. 6, 199034 St. Petersburg, Russian Federation.
authors.forename: Mikhail
authors.initials: M
authors.lastname: Samoilov
authors.affiliation: Laboratory of Regulation of Brain Neuron Functions, Pavlov Institute of Physiology, Russian Academy of Sciences, Makarova nab. 6, 199034 St. Petersburg, Russian Federation.
authors.forename: Anna
authors.initials: A
authors.lastname: Churilova
authors.affiliation: Laboratory of Regulation of Brain Neuron Functions, Pavlov Institute of Physiology, Russian Academy of Sciences, Makarova nab. 6, 199034 St. Petersburg, Russian Federation.
authors.forename: Tatjana
authors.initials: T
authors.lastname: Gluschenko
authors.affiliation: Laboratory of Regulation of Brain Neuron Functions, Pavlov Institute of Physiology, Russian Academy of Sciences, Makarova nab. 6, 199034 St. Petersburg, Russian Federation; Department of Biochemistry, Faculty of Biology, St. Petersburg State University, 7-9, Universitetskaya nab., 199034 St. Petersburg, Russian Federation.
authors.forename: Oleg
authors.initials: O
authors.lastname: Vetrovoy
authors.affiliation: Laboratory of Genetics of High Nervous Activity, Pavlov Institute of Physiology, Russian Academy of Sciences, Makarova nab. 6, 199034 St. Petersburg, Russian Federation.
authors.forename: Natalia
authors.initials: N
authors.lastname: Dyuzhikova
authors.affiliation: Laboratory of Neuroendocrinology, Pavlov Institute of Physiology, Russian Academy of Sciences, Makarova nab. 6, 199034 St. Petersburg, Russian Federation. Electronic address: rybnikova1@rambler.ru.
authors.forename: Elena
authors.initials: E
authors.lastname: Rybnikova
mesh_terms: D000107:Acetylation; D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism; D056547:CA1 Region, Hippocampal / Q000098:blood supply / Q000378:metabolism; D056654:CA3 Region, Hippocampal / Q000098:blood supply / Q000378:metabolism; D015687:Cell Hypoxia; D006657:Histones / Q000378:metabolism*; D008297:Male; D019579:Neocortex / Q000098:blood supply / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D017208:Rats, Wistar
chemical_list: D006657:Histones
keywords: Acetylation of the proteins; Brain hypoxic/ischemic tolerance; Histone H3; Histone acetylation; Hypoxia; Hypoxic preconditioning