Inverse alterations of BCKA dehydrogenase activity in cardiac and skeletal muscles of diabetic rats.
Inverse alterations of BCKA dehydrogenase activity in cardiac and skeletal muscles of diabetic rats.
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糖尿病大鼠心肌和骨骼肌中 BCKA 脱氢酶活性的反向改变。
DOI：
10.1152/ajpendo.1999.277.4.e685
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发表时间：
1999
期刊：
影响因子：
--
通讯作者：
Adibi,SA
中科院分区：
文献类型：
--
作者：
Lombardo,YB;Serdikoff,C;Thamotharan,M;Paul,HS;Adibi,SA
大鼠心肌和骨骼肌作为研究支链α-酮酸（BCKA）氧化调控的模型组织，其BCKA脱氢酶的活性状态差异很大。在本实验中，我们研究了它们的BCKA脱氢酶对代谢改变（如糖尿病）的反应是否也有所不同，如果是的话，我们将研究这种差异背后的机制。对骨骼肌（腓肠肌）中BCKA脱氢酶的研究表明：1)糖尿病使BCKA脱氢酶活性增加，2)使BCKA脱氢酶所有亚基（E1α、E1β、E2）的蛋白和基因表达增加，3)使BCKA脱氢酶活性增加，4)使BCKA脱氢酶失活率降低。5)降低其相关激酶（BCKAD激酶）的蛋白表达，但不影响其基因表达。与此形成鲜明对比的是，对心肌中BCKA脱氢酶的研究表明，糖尿病1)降低了其活性，2)对其任何亚基的蛋白或基因表达均无影响，3)降低了其活性状态，4)增加了其失活率，5)增加了其相关激酶的蛋白和基因表达。总之，我们的数据表明，在糖尿病中，骨骼肌中BCKAD激酶的蛋白表达在转录后下调，而在心肌中，BCKAD激酶的蛋白表达在翻译前上调，导致这些肌肉中BCKA脱氢酶活性的反向改变。
Rat cardiac and skeletal muscles, which have been used as model tissues for studies of regulation of branched-chain α-keto acid (BCKA) oxidation, vary greatly in the activity state of their BCKA dehydrogenase. In the present experiment, we have investigated whether they also vary in response of their BCKA dehydrogenase to a metabolic alteration such as diabetes and, if so, to investigate the mechanism that underlies the difference. Diabetes was produced by depriving streptozotocin-treated rats of insulin administration for 96 h. The investigation of BCKA dehydrogenase in the skeletal muscle (gastrocnemius) showed that diabetes1) increased its activity,2) increased the protein and gene expressions of all of its subunits (E1α, E1β, E2),3) increased its activity state,4) decreased the rate of its inactivation, and5) decreased the protein expression of its associated kinase (BCKAD kinase) without affecting its gene expression. In sharp contrast, the investigation of BCKA dehydrogenase in the cardiac muscle showed that diabetes1) decreased its activity,2) had no effect on either protein or gene expression of any of its subunits,3) decreased its activity state,4) increased its rate of inactivation, and5) increased both the protein and gene expressions of its associated kinase. In conclusion, our data suggest that, in diabetes, the protein expression of BCKAD kinase is downregulated posttranscriptionally in the skeletal muscle, whereas it is upregulated pretranslationally in the cardiac muscle, causing inverse alterations of BCKA dehydrogenase activity in these muscles.