Diabetes-associated nitration of tyrosine and inactivation of succinyl-CoA:3-oxoacid CoA-transferase.
Diabetes-associated nitration of tyrosine and inactivation of succinyl-CoA:3-oxoacid CoA-transferase.
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DOI：
10.1152/ajpheart.2001.281.6.h2289
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发表时间：
2001-12
期刊：
影响因子：
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通讯作者：
I. Turko;Sisi Marcondes;Ferid Murad
中科院分区：
文献类型：
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作者：
I. Turko;Sisi Marcondes;Ferid Murad
糖尿病患者体内高水平的氮和氧的活性物种可能会引起蛋白质的改变。最近，在一些糖尿病组织中发现蛋白质酪氨酸硝化增加。为了了解蛋白质酪氨酸硝化是糖尿病相关并发症的原因还是结果，必须用糖尿病体内模型识别易硝化的特定蛋白质。在本研究中，我们证明了琥珀酰辅酶A：3-氧基辅酶A转移酶(SCOT；EC 2.8.3.5)对链脲佐菌素处理的大鼠心脏的酪氨酸硝化反应敏感。链脲佐菌素给药4wk和8wk以及糖尿病进展后，大鼠心脏的SCOT催化活性分别下降了24%和39%。SCOT催化活性的降低伴随着SCOT蛋白中硝基酪氨酸的积累。SCOT是一种线粒体基质蛋白，负责酮体的利用。在葡萄糖缺乏期间，酮体提供了另一种能量来源。由于糖尿病导致心肌基质利用的严重紊乱，我们认为Scot酪氨酸硝化是糖尿病心脏这种损害的一个促成因素。
High levels of reactive species of nitrogen and oxygen in diabetes may cause modifications of proteins. Recently, an increase in protein tyrosine nitration was found in several diabetic tissues. To understand whether protein tyrosine nitration is the cause or the result of the associated diabetic complications, it is essential to identify specific proteins vulnerable to nitration with in vivo models of diabetes. In the present study, we have demonstrated that succinyl-CoA:3-oxoacid CoA-transferase (SCOT; EC 2.8.3.5) is susceptible to tyrosine nitration in hearts from streptozotocin-treated rats. After 4 and 8 wk of streptozotocin administration and diabetes progression, SCOT from rat hearts had a 24% and 39% decrease in catalytic activity, respectively. The decrease in SCOT catalytic activity is accompanied by an accumulation of nitrotyrosine in SCOT protein. SCOT is a mitochondrial matrix protein responsible for ketone body utilization. Ketone bodies provide an alternative source of energy during periods of glucose deficiency. Because diabetes results in profound derangements in myocardial substrate utilization, we suggest that SCOT tyrosine nitration is a contributing factor to this impairment in the diabetic heart.