PMID- 30322095 OWN - NLM STAT- MEDLINE DCOM- 20190114 LR - 20231004 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 19 IP - 10 DP - 2018 Oct 12 TI - Histone Hyperacetylation as a Response to Global Brain Ischemia Associated with Hyperhomocysteinemia in Rats. LID - 10.3390/ijms19103147 [doi] LID - 3147 AB - Epigenetic regulations play an important role in both normal and pathological conditions of an organism, and are influenced by various exogenous and endogenous factors. Hyperhomocysteinemia (hHcy), as a risk factor for several pathological conditions affecting the central nervous system, is supposed to alter the epigenetic signature of the given tissue, which therefore worsens the subsequent damage. To investigate the effect of hHcy in combination with ischemia-reperfusion injury (IRI) and histone acetylation, we used the hHcy animal model of global forebrain ischemia in rats. Cresyl violet staining showed massive neural disintegration in the M1 (primary motor cortex) region as well as in the CA1 (cornu ammonis 1) area of the hippocampus induced by IRI. Neural loss was significantly higher in the group with induced hHcy. Moreover, immunohistochemistry and Western blot analysis of the brain cortex showed prominent changes in the acetylation of histones H3 and H4, at lysine 9 and 12, respectively, as a result of IRI and induced hHcy. It seems that the differences in histone acetylation patterns in the cortical region have a preferred role in pathological processes induced by IRI associated with hHcy and could be considered in therapeutic strategies. FAU - Tothova, Barbara AU - Tothova B AD - Department of Molecular Medicine, Biomedical Center Martin, Jessenius Faculty of Medicine, Comenius University in Bratislava, 03601 Martin, Slovakia. tothova@jfmed.uniba.sk. FAU - Kovalska, Maria AU - Kovalska M AD - Department of Histology and Embryology, Jessenius Faculty of Medicine, Comenius University in Bratislava, 03601 Martin, Slovakia. kovalska@jfmed.uniba.sk. FAU - Kalenska, Dagmar AU - Kalenska D AD - Department of Medical Biochemistry, Jessenius Faculty of Medicine, Comenius University in Bratislava, 03601 Martin, Slovakia. kalenska@jfmed.uniba.sk. FAU - Tomascova, Anna AU - Tomascova A AD - Department of Medical Biochemistry, Jessenius Faculty of Medicine, Comenius University in Bratislava, 03601 Martin, Slovakia. benova111@uniba.sk. FAU - Lehotsky, Jan AU - Lehotsky J AUID- ORCID: 0000-0002-2408-5745 AD - Department of Medical Biochemistry, Jessenius Faculty of Medicine, Comenius University in Bratislava, 03601 Martin, Slovakia. lehotsky@jfmed.uniba.sk. AD - Department of Neuroscience, Biomedical Center Martin, Jessenius Faculty of Medicine, Comenius University in Bratislava, 03601 Martin, Slovakia. lehotsky@jfmed.uniba.sk. LA - eng PT - Journal Article DEP - 20181012 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (Histones) RN - K3Z4F929H6 (Lysine) SB - IM MH - Acetylation MH - Animals MH - Brain Ischemia/*complications/metabolism MH - Disease Models, Animal MH - Epigenesis, Genetic MH - Hippocampus/metabolism/*pathology MH - Histones/*metabolism MH - Hyperhomocysteinemia/*complications/metabolism MH - Lysine/metabolism MH - Male MH - Rats MH - Rats, Wistar PMC - PMC6214033 OTO - NOTNLM OT - cortex OT - global forebrain ischemia OT - histone acetylation OT - homocysteine (Hcy) OT - ischemia-reperfusion injury (IRI) OT - rat COIS- The authors declare no conflict of interest. EDAT- 2018/10/17 06:00 MHDA- 2019/01/15 06:00 PMCR- 2018/10/01 CRDT- 2018/10/17 06:00 PHST- 2018/09/06 00:00 [received] PHST- 2018/10/05 00:00 [revised] PHST- 2018/10/10 00:00 [accepted] PHST- 2018/10/17 06:00 [entrez] PHST- 2018/10/17 06:00 [pubmed] PHST- 2019/01/15 06:00 [medline] PHST- 2018/10/01 00:00 [pmc-release] AID - ijms19103147 [pii] AID - ijms-19-03147 [pii] AID - 10.3390/ijms19103147 [doi] PST - epublish SO - Int J Mol Sci. 2018 Oct 12;19(10):3147. doi: 10.3390/ijms19103147.