title: MG132 proteasome inhibitor upregulates the expression of connexin 43 in rats with adriamycin-induced heart failure.
abstract: The connexin 43 (Cx43) gap junction protein is important in the synchronization of contraction of cardiac myocytes. Abnormal expression of Cx43 contributes to ventricular arrhythmia, which is the major cause of sudden death in heart failure (HF). Cx43 is known to interact with zonula occludens (ZO)‑1, and the proteasome is involved in the regulation of Cx43 degradation. Although Cx43 is downregulated in heart failure, the underlying mechanisms remain to be elucidated. The present study aimed to investigate the effect of the MG132 proteasome inhibitor on the expression levels of Cx43, ZO‑1, 20S proteasome and ubiquitin in a rat model of HF, induced by adriamycin. MG132 reduced adriamycin‑induced injury in the failing heart. In addition, MG132 inhibited the expression of 20S proteasome and ubiquitin, accompanied by an upregulation in the expression of Cx43 and ZO‑1. These findings suggested that inhibition of the ubiquitin‑proteasome system upregulated the expression of Cx43. Therefore, the proteasome inhibitor may be used to prevent degradation of Cx43 in HF, and thus may prevent Cx43-mediated arrhythmia in HF.
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China.
authors.forename: Guiying
authors.initials: G
authors.lastname: Chen
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China.
authors.forename: Jiyi
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China.
authors.forename: Chunyan
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China.
authors.forename: Yina
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China.
authors.forename: Yanping
authors.initials: Y
authors.lastname: Huo
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China.
authors.forename: Lijun
authors.initials: L
authors.lastname: Zhou
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity*; D002316:Cardiotonic Agents / Q000494:pharmacology*; D018031:Connexin 43 / Q000235:genetics / Q000378:metabolism*; D004317:Doxorubicin / Q000633:toxicity*; D004353:Drug Evaluation, Preclinical; D005786:Gene Expression Regulation / Q000187:drug effects; D006333:Heart Failure / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D007976:Leupeptins / Q000494:pharmacology*; D008297:Male; D061988:Proteasome Inhibitors / Q000494:pharmacology; D017208:Rats, Wistar; D015854:Up-Regulation; D014693:Ventricular Fibrillation / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control; D062826:Zonula Occludens-1 Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D000903:Antibiotics, Antineoplastic; D002316:Cardiotonic Agents; D018031:Connexin 43; C580592:Gja1 protein, rat; D007976:Leupeptins; D061988:Proteasome Inhibitors; C569044:Tjp1 protein, rat; D062826:Zonula Occludens-1 Protein; D004317:Doxorubicin; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde