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首页> 外文期刊>American Journal of Physiology >Metallothionein prevents diabetes-induced cardiac pathological changes, likely via the inhibition of succinyl-CoA:3-ketoacid coenzyme A transferase-1 nitration at Trp374
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Metallothionein prevents diabetes-induced cardiac pathological changes, likely via the inhibition of succinyl-CoA:3-ketoacid coenzyme A transferase-1 nitration at Trp374

机译：金属硫蛋白可通过抑制Trp374的琥珀酰辅酶A：3-酮酸辅酶A转移酶1硝化作用来预防糖尿病引起的心脏病理变化

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We previously demonstrated that metallothionein (MT)-mediated protection from diabetesinduced pathological changes in cardiac tissues is related to suppression of superoxide generation and protein nitration. The present study investigated which diabetes-nitrated protein(s) mediate the development of these pathological changes by identifying the panel of nitrated proteins present in diabetic hearts of wild-type (WT) mice and not in those of cardiac-specific MT-overexpressing transgenic (MT-TG) mice. At 2, 4, 8, and 16 wk after streptozotocin induction of diabetes, histopathological examination of the WT and MT-TG diabetic hearts revealed cardiac structure derangement and remodeling, significantly increased superoxide generation, and 3-nitrotyrosine accumulation. A nitrated protein of 58 kDa, succinyl-CoA:3-ketoacid CoA transferase- 1 (SCOT), was identified by mass spectrometry. Although total SCOT expression was not significantly different between the two types of mice, the diabetic WT hearts showed significantly increased nitration content and dramatically decreased catalyzing activity of SCOT. Although SCOT nitration sites were identified at Tyr76, Tyr117, Tyr135, Tyr226, Tyr368, and Trp374, only Tyr76 and Trp374 were found to be located in the active site by three-dimensional structure modeling. However, only Trp374 showed a significantly different nitration level between the WT and MT-TG diabetic hearts. These results suggest that MT prevention of diabetes-induced pathological changes in cardiac tissues is most likely mediated by suppression of SCOT nitration at Trp374.
机译：我们以前证明金属硫蛋白（MT）介导的保护作用，可防止糖尿病引起的心脏组织病理变化与抑制超氧化物生成和蛋白质硝化有关。本研究通过鉴定野生型（WT）小鼠的糖尿病心脏中而非心脏特异性MT过表达的转基因动物中存在的硝化蛋白质组，研究了哪些糖尿病相关蛋白介导了这些病理变化的发展。 （MT-TG）小鼠。链脲佐菌素诱导糖尿病后第2、4、8和16周，对WT和MT-TG糖尿病心脏的组织病理学检查显示心脏结构紊乱和重塑，超氧化物生成显着增加以及3-硝基酪氨酸积累。通过质谱鉴定了58kDa的硝化蛋白琥珀酰-CoA：3-酮酸CoA转移酶-1（SCOT）。尽管两种类型的小鼠之间总的SCOT表达没有显着差异，但糖尿病WT心脏的硝化含量明显增加，而SCOT的催化活性却大大降低。尽管在Tyr76，Tyr117，Tyr135，Tyr226，Tyr368和Trp374处发现了SCOT硝化位点，但通过三维结构建模仅发现了Tyr76和Trp374位于活性位点。但是，只有Trp374在WT和MT-TG糖尿病心脏之间显示出明显不同的硝化水平。这些结果表明，MT预防糖尿病引起的心脏组织病理变化最可能是通过抑制Trp374处的SCOT硝化作用介导的。

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