Starvation and diabetes increase the amount of pyruvate dehydrogenase kinase isoenzyme 4 in rat heart

Starvation and diabetes increase the amount of pyruvate dehydrogenase kinase isoenzyme 4 in rat heart
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DOI:
10.1042/bj3290197
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发表时间:
1998-01-01
影响因子:
4.1
通讯作者:
Harris, RA
Harris, RA
中科院分区:
生物学3区
文献类型:
--
作者:
Wu, PF;Sato, J;Harris, RA

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本研究调查是否已知改变丙酮酸脱氢酶复合物的活性和磷酸化状态的条件下,有特定的影响丙酮酸脱氢酶激酶(PDK)在大鼠心脏的同工酶的水平。免疫印迹分析显示,饥饿或链脲佐菌素导致糖尿病的大鼠心脏中PDK4的量显著增加。饥饿大鼠的再喂养和糖尿病大鼠的胰岛素治疗非常有效地逆转了PDK4蛋白的增加,并将PDK酶活性恢复到了普通饲料喂养的对照大鼠的水平。饥饿和糖尿病也显著增加了PDK4 mRNA的丰度,并且再喂养和胰岛素治疗降低了对照大鼠的信息水平。PDK1和PDK2蛋白的量以及它们的信息的丰富度在响应饥饿和糖尿病时发生很少或没有变化。所观察到的PDK同工酶相对丰度的变化可能解释了先前关于饥饿和糖尿病对心脏PDK活性影响的研究。结果表明,控制PDK 4的量对于长期调节大鼠心脏丙酮酸脱氢酶复合物活性非常重要。
This study investigated whether conditions known to alter the activity and phosphorylation state of the pyruvate dehydrogenase complex have specific effects on the levels of isoenzymes of pyruvate dehydrogenase kinase (PDK) in rat heart. Immunoblot analysis revealed a remarkable increase in the amount of PDK4 in the hearts of rats that had been starved or rendered diabetic with streptozotocin. Re-feeding of starved rats and insulin treatment of diabetic rats very effectively reversed the increase in PDK4 protein and restored PDK enzyme activity to levels of chow-fed control rats, Starvation and diabetes also markedly increased the abundance of PDK4 mRNA, and re-feeding and insulin treatment reduced levels of the message to that of controls, In contrast with the findings for PDK4, little or no changes in the amounts of PDK1 and PDK2 protein and the abundance of their messages occurred In response to starvation and diabetes. The observed shift in the relative abundance of PDK isoenzymes probably explains previous studies of the effects of starvation and diabetes on heart PDK activity. The results indicate that control of the amount of PDK4 is important in long-term regulation of the activity of the pyruvate dehydrogenase complex in rat heart.