A-kinase anchoring protein 5 anchors protein kinase A to mediate PLN/SERCA to reduce cardiomyocyte apoptosis induced by hypoxia and reoxygenation

Abstract

A-kinase anchoring protein (AKAP) 5 has a variety of biological activities. This study explored whether AKAP5 is involved in cardiomyocyte apoptosis induced by H/R and its possible mechanism. H9C2 cells were used to construct an H/R model in vitro, followed by overexpression of AKAP5 in the cells. Flow cytometry was used to detect the rate of cardiomyocyte apoptosis. The expression of phospholamban (PLN) phosphorylation, SERCA2a and apoptosis-related proteins were determined by western blot. Immunofluorescence staining and immunoprecipitation were used to detect the distribution of and interaction between AKAP5, PKA, and PLN. After H/R induction, H9C2 cells had significantly reduced expression of AKAP5 protein. Upregulation of AKAP5 promoted cell survival and significantly reduced LDH level and apoptosis rate of H9C2 cells. In addition, the overexpression of AKAP5 was accompanied by the activation of the PLN/SERCA2a signaling pathway and a reduction in apoptosis. Immunofluorescence staining and immunoprecipitation revealed that AKAP5 colocalized and interacted with PLN and PKA.Interestingly,St-Ht31 inhibited the effect of AKAP5 overexpression on H/R-induced apoptosis in H9C2 cardiomyocytes. AKAP5 overexpression alleviated H/R-induced cardiomyocyte apoptosis, possibly through anchoring to PKA to mediate the PLN/SERCA pathway, suggesting that AKAP5 is a potential therapeutic target for the prevention and treatment of ischemia-reperfusion injury.

Cardiac transcriptomic changes induced by early CKD in mice reveal novel pathways involved in the pathogenesis of Cardiorenal syndrome type 4

“…In this transcriptomic study, we describe an abundance of changes occurring in the heart after UUO that comprise a broad spectrum of biological processes. Among them, we identified other UUO-upregulated cardiac genes ( Birc5, Cd300E, Foxm1, Spag5, Hmmr, Dach1, Akap5, and Yes1 ) that could advance our understanding of the relationship between kidney disease and cardiac dysfunction due to their involvement in immune responses, cardiac repair, fibrosis, inflammation, proliferation, oxidative stress, and apoptosis [ [30] , [31] , [32] , [33] ]. These genes could provide novel insights into CKD-related cardiac pathways contributing to CRS progression though their direct contribution needs to be validated experimentally.…”