title: Epigenetic Features Induced by Ischemia-Hypoxia in Cultured Rat Astrocytes.
abstract: Epigenetic mechanisms are involved in the maintenance of long-term hypoxia-adapted cellular functions. Astrocytes as the dividing neuroglia cell in the nervous tissue can be activated under hypoxia condition. In the present study, the epigenetic characteristics such as DNA methylation and histone acetylation, as well as S-adenosylmethionine (SAM) role were explored in cultured astrocytes under ischemia-hypoxia (IH) condition. IH could induce the hypermethylation of global DNA and hypoacetylation of histone H3/H4 in an enzyme-dependent manner. c-Jun amino terminal kinase (JNK) signal pathway was involved in this epigenetic change induced by IH. SAM revealed a reverse effect on protein expression without the involvement of methyl donor. On the other hand, neither change of global DNA nor specific gene methylation level was observed in non-dividing neurons under IH condition. In conclusion, a genome-wide adjustment of DNA methylation and histone acetylation under IH conditions should be involved in epigenetic programming of astrocytes. Understanding how ischemia-hypoxia affects global and gene-specific epigenetic programming will provide important insights into the mechanisms of hypoxia-induced cellular changes.
authors.affiliation: Department of Pathology, Key Laboratory for Neurodegenerative Disease of Education Ministry, Capital Medical University, Beijing, 100069, China.
authors.forename: Qinglin
authors.initials: Q
authors.lastname: Yang
authors.affiliation: Department of Pathology, Key Laboratory for Neurodegenerative Disease of Education Ministry, Capital Medical University, Beijing, 100069, China.
authors.forename: Xiangmei
authors.initials: X
authors.lastname: Wu
authors.affiliation: Department of Pathology, Key Laboratory for Neurodegenerative Disease of Education Ministry, Capital Medical University, Beijing, 100069, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Sun
authors.affiliation: Department of Pathology, Key Laboratory for Neurodegenerative Disease of Education Ministry, Capital Medical University, Beijing, 100069, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Cui
authors.affiliation: Department of Pathology, Key Laboratory for Neurodegenerative Disease of Education Ministry, Capital Medical University, Beijing, 100069, China. liliang8698@yeah.net.
authors.forename: Liang
authors.initials: L
authors.lastname: Li
mesh_terms: D000107:Acetylation / Q000187:drug effects; D053829:Amyloid Precursor Protein Secretases / Q000235:genetics / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000873:Anthracenes / Q000494:pharmacology; D016282:Aspartic Acid Endopeptidases / Q000235:genetics / Q000378:metabolism; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D002545:Brain Ischemia / Q000150:complications / Q000235:genetics* / Q000473:pathology*; D002478:Cells, Cultured; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000378:metabolism; D019175:DNA Methylation / Q000187:drug effects / Q000235:genetics; D044127:Epigenesis, Genetic / Q000187:drug effects; D000860:Hypoxia / Q000150:complications / Q000235:genetics* / Q000473:pathology*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D051783:Methyl-CpG-Binding Protein 2 / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D012436:S-Adenosylmethionine / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
chemical_list: D016564:Amyloid beta-Protein Precursor; D000873:Anthracenes; D051783:Methyl-CpG-Binding Protein 2; C432165:pyrazolanthrone; D012436:S-Adenosylmethionine; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509281:Bace1 protein, rat
keywords: Astrocytes; DNA methylation; Histone acetylation; Hypoxia-ischemia; S-adenosylmethionine