High glucose promotes gap junctional communication in cultured neonatal cardiac fibroblasts via AMPK activation

Abstract

Cardiac fibroblasts are known to be essential for adaptiveresponses in the patho- genesis of cardiovascular diseases, and increased intercellular communication of myocardial cells and cardiac fibroblasts acts as a crucial factor in maintaining the functional integrity of the heart. AMP-activated kinase (AMPK) is a key stress signaling kinase, which plays an important role in promoting cell survival and improving cell function. However, the underlying link between AMPK and gap junctional communication (GJIC) is still poorly understood. In this study, a connection between AMPK and GJIC in high glucose-mediated neonatal cardiac fibroblasts was assessed using fibroblast migration, measurement of dye transfer and connexin43 (Cx43) expression. 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR) and Compound C (CC) were used to regulate AMPK activity. The levels of cell migration and Cx43 protein expression in neonatal cardiac fibroblasts increased during high glucose treatment, accompanied by developed dye transfer. In addition, high glucose induced abundant phosphorylation of AMPK. Suppression of AMPK phosphorylation using CC reduced dye transfer, cell migration and Cx43 protein expression in neonatal cardiac fibroblasts, whereas the activation of AMPK using AICAR mimicked the high glucose-mediated cell migration, Cx43 protein expression and dye transfer enhancement. AMPK appears to participate in regulating GJIC in high-glucose-treated neonatal cardiac fibroblasts, including cell migration, dye transfer, Cx43 expression and distribution.