Yang Xiaojuan, Song Jing, Yan Liang-Jun
Department of Pharmaceutical Sciences, UNT System College of Pharmacy, University of North Texas Health Science Center, Fort Worth, TX 76107, USA.
Antioxidants (Basel). 2019 Feb 2;8(2):32. doi: 10.3390/antiox8020032.
Mitochondrial dihydrolipoamide dehydrogenase (DLDH) is a redox enzyme involved in decarboxylation of pyruvate to form acetyl-CoA during the cascade of glucose metabolism and mitochondrial adenine triphosphate (ATP) production. Depending on physiological or pathophysiological conditions, DLDH can either enhance or attenuate the production of reactive oxygen species (ROS) and reactive nitrogen species. Recent research in our laboratory has demonstrated that inhibition of DLDH induced antioxidative responses and could serve as a protective approach against oxidative stress in stroke injury. In this perspective article, we postulated that chronic inhibition of DLDH could also attenuate oxidative stress in type 2 diabetes. We discussed DLDH-involving mitochondrial metabolic pathways and metabolic intermediates that could accumulate upon DLDH inhibition and their corresponding roles in abrogating oxidative stress in diabetes. We also discussed a couple of DLDH inhibitors that could be tested in animal models of type 2 diabetes. It is our belief that DLDH inhibition could be a novel approach to fighting type 2 diabetes.
线粒体二氢硫辛酰胺脱氢酶（DLDH）是一种氧化还原酶，在葡萄糖代谢级联反应和线粒体三磷酸腺苷（ATP）生成过程中，参与丙酮酸脱羧形成乙酰辅酶A。根据生理或病理生理条件，DLDH既可以增强也可以减弱活性氧（ROS）和活性氮的生成。我们实验室最近的研究表明，抑制DLDH可诱导抗氧化反应，并可作为一种针对中风损伤氧化应激的保护方法。在这篇观点文章中，我们推测，长期抑制DLDH也可能减轻2型糖尿病中的氧化应激。我们讨论了涉及DLDH的线粒体代谢途径以及DLDH抑制后可能积累的代谢中间体，以及它们在消除糖尿病氧化应激中的相应作用。我们还讨论了几种可在2型糖尿病动物模型中进行测试的DLDH抑制剂。我们相信，抑制DLDH可能是对抗2型糖尿病的一种新方法。
