Chronic inhibition of mitochondrial dihydrolipoamide dehydrogenase (DLDH) as an approach to managing diabetic oxidative stress

Xiaojuan Yang, Jing Song, Liang-Jun Yan

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Article number32
JournalAntioxidants
Volume8
Issue number2
DOIs
StatePublished - 1 Jan 2019

Fingerprint

Dihydrolipoamide Dehydrogenase
Oxidative stress
Oxidative Stress
Medical problems
Type 2 Diabetes Mellitus
Reactive Nitrogen Species
Acetyl Coenzyme A
Decarboxylation
Adenine
Metabolic Networks and Pathways
Pyruvic Acid
Metabolism
Oxidation-Reduction
Reactive Oxygen Species
Animals
Animal Models
Stroke
Glucose

Keywords

  • Diabetes mellitus
  • Dihydrolipoamide dehydrogenase
  • Mitochondria
  • Oxidative stress
  • Reactive oxygen species

Cite this

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abstract = "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.",
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Chronic inhibition of mitochondrial dihydrolipoamide dehydrogenase (DLDH) as an approach to managing diabetic oxidative stress. / Yang, Xiaojuan; Song, Jing; Yan, Liang-Jun.

In: Antioxidants, Vol. 8, No. 2, 32, 01.01.2019.

Research output: Contribution to journalArticle

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