Regulation of SERCA2a by Akt in alcoholic cardiomyopathy

Abstract

Alcoholic cardiomyopathy is one of the leading causes of non‐ischemic dilated cardiomyopathy. Approximately one in three alcoholics develops this disease. Prior studies from our lab have demonstrated the up‐regulation of intracellular calcium in dilated cardiomyopathy by Akt. SERCA2a has shown to be reduced in heart failure. Thus, we hypothesize that alcohol regulates the SERCA2a activity via the Akt pathway, affecting Ca2+ handling in cardiocytes. Thus, parallel measures of intracellular Ca2+ and sarcomere/cellular contractions were assessed (Ionoptix) with the expression level (western blot) of primary Ca2+ handling proteins (SERCA2a, phospholamban, ryanodine receptors, Na/Ca exchanger and L‐type Ca2+ channels) from control, low (LA: 0.02%), moderate (MA: 0.11%) and high (HA: 0.45%) alcoholic rat hearts with and without Ad. EGFP, Ad. Akt and Ad.Akt(K179M) transfection. Our studies indicate that SERCA2a levels are decreased in MA and HA hearts as well as those transfected with Ad.Akt. This suggests that elevated alcohol exposure induces cardiac dysfunction partly through reduction of SERCA2a activity in an Akt‐dependent manner.This work was supported in part by grants NIH/NIAAA/1R15AAA019816–01A1 and 2G12 RR003048RCMI/NCRR/NIH.