title: Remifentanil postconditioning ameliorates histone H3 acetylation modification in H9c2 cardiomyoblasts after hypoxia/reoxygenation via attenuating endoplasmic reticulum stress.
abstract: Remifentanil postconditioning (RPC) elicits cardioprotection against ischemia/reperfusion injury (IRI) by attenuating apoptosis associated with endoplasmic reticulum stress (ERS). Histone H3, acetylation modifications of histone H3, and histone deacetylases (HDAC) also have key roles in the mediation of the survival and apoptosis of cardiomyocytes. In this study, an in vitro IRI model was established with H9c2 cardiomyoblasts to investigate the role of histone H3 acetylation and HDAC3 in RPC-induced attenuation of ERS-associated apoptosis. Briefly, H9c2 cardiomyoblasts were randomly subjected to hypoxia/reoxygenation with and without remifentanil administered at the onset of reoxygenation. Results showed that RPC increased cell viability and prevented cell apoptosis (evidenced by CCK-8 cell viability assays and flow cytometry), and these effects were accompanied by lower levels of expression of GRP78, CHOP, cleaved caspase-12, and cleaved caspase-3. RPC also mimicked the effects of SAHA by increasing the amount of histone H3 deacetylation and decreasing up-regulation of HDAC at both the mRNA and protein levels in response to HR. Finally, RPC-induced protective effects against HR, including attenuation of ERS-associated protein markers, deacetylation of histone H3, and down-regulation of HDAC3 were completely abolished by pretreatment with thapsigargin (TG, a specific ERS activator). In contrast, these effects were not found to be enhanced after pretreatment with 4-phenyl butyric acid (4-PBA, a widely used ERS inhibitor). The present results demonstrate that RPC protects H9c2 cardiomyoblasts from HR injury, and this protection involves an attenuation of ERS-associated apoptosis, which mediates a reduction in HDAC3 expression and an increase in histone H3 deacetylation.
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital, Medical School of Zhejiang University, Hangzhou, China.|Department of Anesthesiology, The First Affiliated Hospital of Anhui Medical University, No. 218 Jixi Road, Hefei, Anhui, China.
authors.forename: Manli
authors.initials: M
authors.lastname: Chen
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital of Anhui Medical University, No. 218 Jixi Road, Hefei, Anhui, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital of Anhui Medical University, No. 218 Jixi Road, Hefei, Anhui, China.
authors.forename: Lijian
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital of Anhui Medical University, No. 218 Jixi Road, Hefei, Anhui, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital of Anhui Medical University, No. 218 Jixi Road, Hefei, Anhui, China. ay_guew_mz@163.com.
authors.forename: Erwei
authors.initials: E
authors.lastname: Gu
mesh_terms: D000107:Acetylation / Q000187:drug effects; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000235:genetics; D015687:Cell Hypoxia / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D005786:Gene Expression Regulation / Q000187:drug effects; D006360:Heat-Shock Proteins / Q000235:genetics; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D032386:Myoblasts, Cardiac / Q000187:drug effects / Q000378:metabolism; D010880:Piperidines / Q000008:administration & dosage*; D051381:Rats; D000077208:Remifentanil; D015427:Reperfusion Injury / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D051742:Transcription Factor CHOP / Q000235:genetics
chemical_list: C497251:Ddit3 protein, rat; D000091342:Endoplasmic Reticulum Chaperone BiP; C051684:GRP78 protein, rat; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; D006657:Histones; D010880:Piperidines; D051742:Transcription Factor CHOP; D020169:Caspases; D000077208:Remifentanil
keywords: Apoptosis; Cardioprotection; Endoplasmic reticulum stress; HDAC3; Histone 3; Remifentanil postconditioning