Adenylate cyclase 1 knockdown attenuates pirarubicin‐induced cardiotoxicity

Abstract

AbstractThis study aimed to investigate the effects and possible mechanisms of adenylate cyclase 1 (ADCY1) on pirarubicin‐induced cardiomyocyte injury. HL‐1 cells were treated with pirarubicin (THP) to induce intracellular toxicity, and the extent of damage to mouse cardiomyocytes was assessed using CCK‐8, Edu, flow cytometry, ROS, ELISA, RT‐qPCR and western blotting. THP treatment reduced the viability of HL‐1 cells, inhibited proliferation, induced apoptosis and triggered oxidative stress. In addition, the RT‐qPCR results revealed that ADCY1 expression was significantly elevated in HL‐1 cells, and molecular docking showed a direct interaction between ADCY1 and THP. Western blotting showed that ADCY1, phospho‐protein kinase A and GRIN2D expression were also significantly elevated. Knockdown of ADCY1 attenuated THP‐induced cardiotoxicity, possibly by regulating the ADCY1/PKA/GRIN2D pathway.