Epigenetic Features Induced by Ischemia-Hypoxia in Cultured Rat Astrocytes

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.