Document Type
Article
Publication Date
2009
College/Unit
School of Medicine
Department/Program/Center
Physiology, Pharmacology & Neuroscience
Abstract
Background
Diabetes has become the single most common cause for end-stage renal disease in the United States. It has been established that mitochondrial damage occurs during diabetes; however, little is known about what initiates mitochondrial injury and oxidant production during the early stages of diabetes. Inactivation of mitochondrial respiratory complexes or alteration of their critical subunits can lead to generation of mitochondrial oxidants, mitochondrial damage, and organ injury. Thus, one goal of this study was to determine the status of mitochondrial respiratory complexes in the rat kidney during the early stages of diabetes (5-weeks post streptozotocin injection).
Methods
Mitochondrial complex activity assays, blue native gel electrophoresis (BN-PAGE), Complex III immunoprecipitation, and an ATP assay were performed to examine the effects of diabetes on the status of respiratory complexes and energy levels in renal mitochondria. Creatinine clearance and urine albumin excretion were measured to assess the status of renal function in our model.
Results
Interestingly, of all four respiratory complexes only cytochrome c reductase (Complex-III) activity was significantly decreased, whereas two Complex III subunits, Core 2 protein and Rieske protein, were up regulated in the diabetic renal mitochondria. The BN-PAGE data suggested that Complex III failed to assemble correctly, which could also explain the compensatory upregulation of specific Complex III subunits. In addition, the renal F0F1-ATPase activity and ATP levels were increased during diabetes.
Conclusion
In summary, these findings show for the first time that early (and selective) inactivation of Complex-III may contribute to the mitochondrial oxidant production which occurs in the early stages of diabetes.
Digital Commons Citation
Munusamy, Shankar; Saba, Hamida; Mitchell, Tanecia; Megyesi, Judit K.; Brock, Robert W.; and MacMillian-Crow, Lee A., "Alteration of renal respiratory Complex-III during experimental type-1 diabetes" (2009). Faculty & Staff Scholarship. 2860.
https://researchrepository.wvu.edu/faculty_publications/2860
Source Citation
Munusamy, S., Saba, H., Mitchell, T. et al. Alteration of renal respiratory Complex-III during experimental type-1 diabetes. BMC Endocr Disord 9, 2 (2009). https://doi.org/10.1186/1472-6823-9-2
Comments
© 2009 Munusamy et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.