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Impaired Mitochondrial Respiratory Functions and Oxidative Stress in Streptozotocin-Induced Diabetic Rats
Department of Biochemistry, Faculty of Medicine and Health Sciences, UAE University, Al Ain, United Arab Emirates
Department of Animal Biology, School of Veterinary Medicine, 3800 Spruce Street, University of Pennsylvania, Philadelphia, PA 19104, USA
* Authors to whom correspondence should be addressed.
Received: 14 March 2011; in revised form: 11 April 2011 / Accepted: 29 April 2011 / Published: 13 May 2011
Abstract: We have previously shown a tissue-specific increase in oxidative stress in the early stages of streptozotocin (STZ)-induced diabetic rats. In this study, we investigated oxidative stress-related long-term complications and mitochondrial dysfunctions in the different tissues of STZ-induced diabetic rats (>15 mM blood glucose for 8 weeks). These animals showed a persistent increase in reactive oxygen and nitrogen species (ROS and RNS, respectively) production. Oxidative protein carbonylation was also increased with the maximum effect observed in the pancreas of diabetic rats. The activities of mitochondrial respiratory enzymes ubiquinol: cytochrome c oxidoreductase (Complex III) and cytochrome c oxidase (Complex IV) were significantly decreased while that of NADH:ubiquinone oxidoreductase (Complex I) and succinate:ubiquinone oxidoreductase (Complex II) were moderately increased in diabetic rats, which was confirmed by the increased expression of the 70 kDa Complex II sub-unit. Mitochondrial matrix aconitase, a ROS sensitive enzyme, was markedly inhibited in the diabetic rat tissues. Increased expression of oxidative stress marker proteins Hsp-70 and HO-1 was also observed along with increased expression of nitric oxide synthase. These results suggest that mitochondrial respiratory complexes may play a critical role in ROS/RNS homeostasis and oxidative stress related changes in type 1 diabetes and may have implications in the etiology of diabetes and its complications.
Keywords: diabetes; oxidative stress; ROS; NO; mitochondrial respiration
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MDPI and ACS Style
Raza, H.; Prabu, S.K.; John, A.; Avadhani, N.G. Impaired Mitochondrial Respiratory Functions and Oxidative Stress in Streptozotocin-Induced Diabetic Rats. Int. J. Mol. Sci. 2011, 12, 3133-3147.
Raza H, Prabu SK, John A, Avadhani NG. Impaired Mitochondrial Respiratory Functions and Oxidative Stress in Streptozotocin-Induced Diabetic Rats. International Journal of Molecular Sciences. 2011; 12(5):3133-3147.
Raza, Haider; Prabu, Subbuswamy K.; John, Annie; Avadhani, Narayan G. 2011. "Impaired Mitochondrial Respiratory Functions and Oxidative Stress in Streptozotocin-Induced Diabetic Rats." Int. J. Mol. Sci. 12, no. 5: 3133-3147.