O-GlcNAcylation was first found by Torres and Hart in monocytes. It is a dynamic and reversible post-translational modification catalyzed by O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA). O-GlcNAcylation is increased in diabetic cardiomyopathy (DCM) patients and it has been reported that OGT plays an important role in the regulation of cardiac gene transcription, cell cycle and calcium homeostasis. The purpose of this study is to investigate the effects of OGT on signal transduction and function of β1-adrenoceptor (β1AR) in adult rat cardiomyocytes. We found that after overexpressing OGT by adenovirus vector in adult rat cardiomyocytes, cAMP formation and phosphorylation of phospholamban (PLB) at Ser16 (p16-PLB) were decreased under isoprenaline (ISO) stimulation. Over expression of OGT increased the intracellular [Ca²⁺]i and deteriorated the death of cardiomyocytes induced by prolonged stimulation with ISO. β1-adrenoceptor was overexpressed using a plasmid vector and then co-immunoprecipitation (co-IP) followed by Western blot was employed to define the O-GlcNAcylation of β1-adrenoceptor. The results showed that O-GlcNAcylation of β1-adrenoceptor was increased in OGT overexpressed cells, and there was no significant change in the formation of cAMP and phosphorylation of PLB after β1-adrenoceptor was blocked by CGP20712A. Given that OGT affects the signal transduction of β1-adrenoceptor in adult rat cardiomyocytes by increasing the O-GlcNAcylation of β1-adrenoceptor, the mechanism revealed in this study indicates that OGT and β1AR may be therapeutic targets in patients undergoing diabetic cardiomyopathy.

O-GlcNAcylation最早是由Torres和Hart在单核细胞中发现的。它是由O-GlcNAc转移酶（OGT）和O-GlcNAcase（OGA）催化的动态且可逆的翻译后修饰。O-GlcNAcylation在糖尿病性心肌病（DCM）患者中增加，并且据报道OGT在调节心脏基因转录，细胞周期和钙稳态中起着重要作用。这项研究的目的是研究OGT对成年大鼠心肌细胞信号传导和β1-肾上腺素能受体（β1AR）功能的影响。我们发现，在成年大鼠心肌细胞中腺病毒载体过表达OGT后，在异丙肾上腺素（ISO）刺激下，Ser16（p16-PLB）的cAMP形成和磷酸lamban（PLB）的磷酸化降低。OGT的过度表达增加了细胞内[Ca ²⁺] i并恶化了ISO长时间刺激引起的心肌细胞死亡。使用质粒载体过表达β1-肾上腺素受体，然后使用共免疫沉淀（co-IP）和Western印迹法定义β1-肾上腺素受体的O-GlcNAcylation。结果表明，CGT20712A阻断了β1-肾上腺素受体后，OGT过表达的细胞中β1-肾上腺素受体的O-GlcNAcy化增加，而cAMP的形成和PLB磷酸化没有明显变化。鉴于OGT通过增加β1-肾上腺素受体的O-GlcNAcy化来影响成年大鼠心肌细胞中β1-肾上腺素受体的信号转导，因此该机制揭示了OGT和β1AR可能是糖尿病性心肌病患者的治疗靶标。