Apelin Ameliorates High Glucose-Induced Downregulation of Connexin 43 via AMPK-Dependent Pathway in Neonatal Rat Cardiomyocytes

作者：Li, Xiaoting; Yu, Lu; Gao, Jing; Bi, Xukun; Zhang, Juhong; Xu, Shiming; Wang, Meihui; Chen, Mengmeng; Qiu, Fuyu; Fu, Guosheng^*

来源：Aging and Disease, 2018, 9(1): 66-76.

DOI：10.14336/AD.2017.0426

• cardiomyocytes
• connexin 43
• high glucose
• apelin
• gap junction
• AMPK

Diabetes Mellitus is a common disorder, with increasing risk of cardiac arrhythmias. Studies have shown that altered connexin expression and gap junction remodeling under hyperglycemia contribute to the high prevalence of cardiac arrhythmias and even sudden death. Connexin 43 (Cx43), a major protein that assembles to form cardiac gap junctions, has been found to be downregulated under high glucose conditions, along with inhibition of gap junctional intercellular communication (GJIC). While, apelin, a beneficial adipokine, increases Cx43 protein expression in mouse and human embryonic stem cells during cardiac differentiation. However, it remains unknown whether apelin influences GJIC capacity in cardiomyocytes. Here, using Western blotting and dye transfer assays, we found that Cx43 protein expression was reduced and GJIC was impaired after treatment with high glucose, which, however, could be abrogated after apelin treatment for 48 h. We also found that apelin increased Cx43 expression under normal glucose. Real-time PCR showed that the Cx43 mRNA was not significantly affected under high glucose conditions in the presence of apelin or high glucose and apelin. High glucose decreased the phosphorylation of AMPK alpha; however, apelin activated AMPK alpha. Interestingly, we found that Cx43 expression was increased after treatment with AICAR, an activator of AMPK signaling. AMPK alpha inhibition mediated with transfection of siRNA-AMPK alpha 1 and siRNA-AMPK alpha 2 abolished the protective effect of apelin on Cx43 expression. Our data suggest that apelin attenuates high glucose-induced Cx43 downregulation and improves the loss of functional gap junctions partly through the AMPK pathway.

• 出版日期2018-2
• 单位浙江大学