Impaired mitochondrial respiratory functions and oxidative stress in streptozotocin-induced diabetic rats.
Bottom Line: These animals showed a persistent increase in reactive oxygen and nitrogen species (ROS and RNS, respectively) production.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.
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.
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Mentions: Tissues from diabetic rats exhibited a modest but significant increase (20–35%; P < 0.05) in oxidative carbonylation of proteins (Figure 3). Mitochondria from pancreas and kidney (Figure 3a) appear to be more affected (30–35% increase) than liver and brain (∼20% increase). On the other hand, a marked increase in microsomal protein carbonylation in pancreas, liver and kidney (about 2–3 fold) was observed, while brain exhibited only about a 20% increase in carbonylated proteins (Figure 3b). Cytosolic fraction also showed a significant increase in protein carbonylation in pancreas and kidney from diabetic tissues while brain and liver exhibited a marginal increase (15–20%) (Figure 3c).