MG132 proteasome inhibitor upregulates the expression of connexin 43 in rats with adriamycin-induced heart failure

Chen,Guiying; Zhao,Jiyi; Liu,Chunyan; Zhang,Yina; Huo,Yanping; Zhou,Lijun

doi:10.3892/mmr.2015.4337

MG132 proteasome inhibitor upregulates the expression of connexin 43 in rats with adriamycin-induced heart failure

Authors:
- Guiying Chen
- Jiyi Zhao
- Chunyan Liu
- Yina Zhang
- Yanping Huo
- Lijun Zhou
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Affiliations: Department of Cardiology, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China
Published online on: September 21, 2015 https://doi.org/10.3892/mmr.2015.4337
Pages: 7595-7602

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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.

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