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Impaired mitochondrial respiratory functions and oxidative stress in streptozotocin-induced diabetic rats.

Raza H, Prabu SK, John A, Avadhani NG - Int J Mol Sci (2011)

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.

View Article: PubMed Central - PubMed

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.

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Succinate-dependent oxygen uptake by mitochondria from control and diabetic rats. Succinate-dependent oxygen consumption by freshly prepared mitochondria from control and diabetic rats in the presence (State 3) or absence of ADP (State 4) was measured as described in the Materials and Methods (a). Respiratory Control Rate (RCR) was calculated as the ratio of State 3/State 4 respiration (b) and expressed relative to control rats. The values are mean ± S.E.M. of three independent experiments. * indicate significant difference (P < 0.05) from control animals. (□) Control; (▪) Diabetic.
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f5-ijms-12-03133: Succinate-dependent oxygen uptake by mitochondria from control and diabetic rats. Succinate-dependent oxygen consumption by freshly prepared mitochondria from control and diabetic rats in the presence (State 3) or absence of ADP (State 4) was measured as described in the Materials and Methods (a). Respiratory Control Rate (RCR) was calculated as the ratio of State 3/State 4 respiration (b) and expressed relative to control rats. The values are mean ± S.E.M. of three independent experiments. * indicate significant difference (P < 0.05) from control animals. (□) Control; (▪) Diabetic.

Mentions: We also determined O2 consumption as an index for mitochondrial respiratory function in diabetic rats. As shown in Figure 5a, the ADP-coupled State 3 respiration was increased in all the tissues in diabetic rats. However, the respiratory control ratio (RCR) of State 3 over State 4 was significantly inhibited (18–32%; P < 0.05) in diabetic rats (Figure 5b).


Impaired mitochondrial respiratory functions and oxidative stress in streptozotocin-induced diabetic rats.

Raza H, Prabu SK, John A, Avadhani NG - Int J Mol Sci (2011)

Succinate-dependent oxygen uptake by mitochondria from control and diabetic rats. Succinate-dependent oxygen consumption by freshly prepared mitochondria from control and diabetic rats in the presence (State 3) or absence of ADP (State 4) was measured as described in the Materials and Methods (a). Respiratory Control Rate (RCR) was calculated as the ratio of State 3/State 4 respiration (b) and expressed relative to control rats. The values are mean ± S.E.M. of three independent experiments. * indicate significant difference (P < 0.05) from control animals. (□) Control; (▪) Diabetic.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC3116180&req=5

f5-ijms-12-03133: Succinate-dependent oxygen uptake by mitochondria from control and diabetic rats. Succinate-dependent oxygen consumption by freshly prepared mitochondria from control and diabetic rats in the presence (State 3) or absence of ADP (State 4) was measured as described in the Materials and Methods (a). Respiratory Control Rate (RCR) was calculated as the ratio of State 3/State 4 respiration (b) and expressed relative to control rats. The values are mean ± S.E.M. of three independent experiments. * indicate significant difference (P < 0.05) from control animals. (□) Control; (▪) Diabetic.
Mentions: We also determined O2 consumption as an index for mitochondrial respiratory function in diabetic rats. As shown in Figure 5a, the ADP-coupled State 3 respiration was increased in all the tissues in diabetic rats. However, the respiratory control ratio (RCR) of State 3 over State 4 was significantly inhibited (18–32%; P < 0.05) in diabetic rats (Figure 5b).

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.

View Article: PubMed Central - PubMed

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.

Show MeSH
Related in: MedlinePlus