Inhibition of phospholamban phosphorylation by O-GlcNAcylation: implications for diabetic cardiomyopathy

• DOI: 10.1093/glycob/cwq071
• Publication Date: 2010-05-19T02:57:07Z
• Authors: S. Yokoe; M. Asahi; T. Takeda; K. Otsu; N. Taniguchi; E. Miyoshi; K. Suzuki
• Keywords: Phospholamban; Immunoprecipitation; Contractility

Cardiac-type sarco(endo)plasmic reticulum Ca2-ATPase (SERCA2a) plays a major role in cardiac muscle contractility. Phospholamban (PLN) regulates the function of SERCA2a via its Ser16-phosphorylation. Since it has been proposed that Ser/Thr residues on cytoplasmic and nuclear proteins are modified by O-linked N-acetylglucosamine (O-GlcNAc), we examined effect O-GlcNAcylation PLN rat adult cardiomyocytes. Studies using enzymatic labeling co-immunoprecipitation wild type series mutants showed was O-GlcNAcylated Ser16 might be site for O-GlcNAcylation. In cardiomyocytes treated with O-(2-acetamido-2-deoxy-d-glucopyranosylidene)amino-N-phenylcarbamate (PUGNAc), significantly increased compared to non-treated cells. Simultaneously, Ser16-phosphorylation reduced. Chinese hamster ovary cells where cDNA O-GlcNAc transferase siRNA were co-transfected, controls. The same results observed heart homogenates from diabetic rats. SERCA2a, physical interaction between two PUGNAc-treated Unlike cells, activity profiles calcium transients not changed even after treatment catecholamine. These data suggest is induce inhibition phosphorylation, which correlates deterioration function. This define novel mechanism regulation altered under conditions increased, such as those occurring diabetes.