title: Redox imbalance and mitochondrial abnormalities in the diabetic lung.
abstract: Although the lung is one of the least studied organs in diabetes, increasing evidence indicates that it is an inevitable target of diabetic complications. Nevertheless, the underlying biochemical mechanisms of lung injury in diabetes remain largely unexplored. Given that redox imbalance, oxidative stress, and mitochondrial dysfunction have been implicated in diabetic tissue injury, we set out to investigate mechanisms of lung injury in diabetes. The objective of this study was to evaluate NADH/NAD+redox status, oxidative stress, and mitochondrial abnormalities in the diabetic lung. Using STZ induced diabetes in rat as a model, we measured redox-imbalance related parameters including aldose reductase activity, level of poly ADP ribose polymerase (PAPR-1), NAD+content, NADPH content, reduced form of glutathione (GSH), and glucose 6-phophate dehydrogenase (G6PD) activity. For assessment of mitochondrial abnormalities in the diabetic lung, we measured the activities of mitochondrial electron transport chain complexes I to IV and complex V as well as dihydrolipoamide dehydrogenase (DLDH) content and activity. We also measured the protein content of NAD+dependent enzymes such as sirtuin3 (sirt3) and NAD(P)H: quinone oxidoreductase 1 (NQO1). Our results demonstrate that NADH/NAD+redox imbalance occurs in the diabetic lung. This redox imbalance upregulates the activities of complexes I to IV, but not complex V; and this upregulation is likely the source of increased mitochondrial ROS production, oxidative stress, and cell death in the diabetic lung. These results, together with the findings that the protein contents of DLDH, sirt3, and NQO1 all are decreased in the diabetic lung, demonstrate that redox imbalance, mitochondrial abnormality, and oxidative stress contribute to lung injury in diabetes.
authors.affiliation: Department of Pharmaceutical Sciences, UNT System College of Pharmacy, University of North Texas Health Science Center, Fort Worth, TX 76107, United States.
authors.forename: Jinzi
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Pharmaceutical Sciences, UNT System College of Pharmacy, University of North Texas Health Science Center, Fort Worth, TX 76107, United States.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Jin
authors.affiliation: Department of Pharmaceutical Sciences, UNT System College of Pharmacy, University of North Texas Health Science Center, Fort Worth, TX 76107, United States. Electronic address: liang-jun.yan@unthsc.edu.
authors.forename: Liang-Jun
authors.initials: LJ
authors.lastname: Yan
mesh_terms: D000818:Animals; D003920:Diabetes Mellitus / Q000235:genetics / Q000378:metabolism*; D008058:Dihydrolipoamide Dehydrogenase / Q000235:genetics*; D042967:Electron Transport Complex I / Q000235:genetics / Q000378:metabolism; D005954:Glucosephosphate Dehydrogenase / Q000235:genetics; D005978:Glutathione / Q000235:genetics; D006801:Humans; D008168:Lung / Q000378:metabolism* / Q000473:pathology; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D009243:NAD / Q000378:metabolism; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000235:genetics*; D009249:NADP / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000235:genetics; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics; D051381:Rats; D037761:Sirtuins / Q000235:genetics*
chemical_list: C000607791:SIRT3 protein, rat; D009243:NAD; D009249:NADP; D005954:Glucosephosphate Dehydrogenase; D016660:NAD(P)H Dehydrogenase (Quinone); C507703:NQO1 protein, rat; D008058:Dihydrolipoamide Dehydrogenase; D011065:Poly(ADP-ribose) Polymerases; D037761:Sirtuins; D042967:Electron Transport Complex I; D005978:Glutathione
keywords: Diabetes; Lung injury; Mitochondrial abnormalities; Oxidative stress; Redox imbalance