Taira Y, Ganguly P K, Panagia V, Dhalla N S
Division of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, Winnipeg, Manitoba, Canada.
Am J Physiol. 1988 Sep;255(3 Pt 1):E347-52. doi: 10.1152/ajpendo.1988.255.3.E347.
Phosphatidylethanolamine (PE) N-methylation was studied in skeletal muscle sarcoplasmic reticulum (SR) 6 wk after the induction of experimental diabetes in rats by an injection of streptozocin (65 mg/kg iv). A significant increase in the incorporation of radiolabeled methyl groups from S-adenosyl-L-methionine (AdoMet) into intramembranal PE was observed in diabetic preparations at 0.055 microM AdoMet, whereas the methylation activity was unaltered at 10 and 150 microM AdoMet concentrations. The increase in PE N-methylation activity was not evident until 28 days after streptozocin injection and was normalized by a 2-wk treatment of diabetic animals with insulin. In the presence of 10 microM of ATP and low concentrations of Ca2+ (0.1 microM), PE N-methylation was maximally activated, but the percent increase was similar in control, diabetes, and insulin-treated diabetes; at 100 microM Ca2+, however, N-methylation activity was depressed only in diabetic preparations. Calmodulin inhibitors such as compound 48/80 and calmidazolium (compound R24571) abolished the effect of Ca2+ and ATP on PE N-methylation in all three groups. Sarcolemmal (SL) PE N-methylation in diabetic skeletal muscle was also found to be increased at 0.055 microM AdoMet. The results suggest that intramembranal calmodulin may participate in regulating PE N-methylation in skeletal muscle membranes, but it may not be responsible for the high N-methylation activity in diabetic rats.
通过静脉注射链脲佐菌素（65 mg/kg）诱导大鼠实验性糖尿病6周后，研究了骨骼肌肌浆网（SR）中磷脂酰乙醇胺（PE）的N-甲基化。在糖尿病制剂中，当腺苷甲硫氨酸（AdoMet）浓度为0.055 microM时，观察到放射性标记的甲基从S-腺苷-L-甲硫氨酸掺入膜内PE的量显著增加，而在10 microM和150 microM AdoMet浓度下，甲基化活性未改变。直到链脲佐菌素注射后28天，PE N-甲基化活性的增加才明显，并且用胰岛素对糖尿病动物进行2周治疗后该活性恢复正常。在存在10 microM ATP和低浓度Ca2+（0.1 microM）的情况下，PE N-甲基化被最大程度激活，但对照组、糖尿病组和胰岛素治疗的糖尿病组的增加百分比相似；然而，在100 microM Ca2+时，N-甲基化活性仅在糖尿病制剂中受到抑制。钙调蛋白抑制剂如化合物48/80和氯米达唑（化合物R24571）消除了Ca2+和ATP对所有三组中PE N-甲基化的影响。还发现糖尿病骨骼肌中的肌膜（SL）PE N-甲基化在0.055 microM AdoMet时也增加。结果表明，膜内钙调蛋白可能参与调节骨骼肌膜中的PE N-甲基化，但它可能不是糖尿病大鼠中高N-甲基化活性的原因。
