Identifying the enzymes that regulate acetylation of sarco(endo)plasmic reticulum calcium ATPase 2a (SERCA2a)
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The Sarco(endo)plasmic Reticulum Calcium ATPase 2a (SERCA2a) is the primary cardiomyocyte calcium transporter and has been shown to be acetylated at higher levels in the diabetic mouse heart. The objective of this study was to determine if SERCA2a acetylation changes with high glucose exposure, which enzyme(s) deacetylate SERCA2a, and which enzyme(s) acetylate SERCA2a. We hypothesized that increased SERCA2a acetylation will have a negative effect on SERCA2a function and that the activities of histone acetyltransferases (HATs) and histone deacetylases (HDACs) regulate SERCA2a acetylation. Our data demonstrates that high glucose increases SERCA2a acetylation and leads to decreased SERCA2a activity in primary rat cardiomyocytes. SERCA2a acetylation increased with inhibition of the sirtuins but Class I & II HDACs. SERCA2a acetylation decreased with pan-inhibition of histone acetyltransferases (HATs) and inhibition of GCN5 prior to glucose exposure. Together this data identifies the sirtuins and GCN5 as possible therapeutic targets to decrease SERCA2a acetylation.