| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY, USA; Department of Pediatrics, University of Louisville, Louisville, KY, USA
2 Department of Pediatrics, University of Louisville, Louisville, KY, USA
3 Core Proteomics Laboratory, Kidney Disease Program, Department of Medicine, University of Louisville, Louisville, KY, USA; Medical Molecular Biology Unit, Office for Reaseach and Development, Faculty of Medicine at Siriraj Hospital, Mahidol University, Bangkok, Thailand
4 Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY, USA
5 Core Proteomics Laboratory, Kidney Disease Program, Department of Medicine, University of Louisville, Louisville, KY, USA; Veterans Affairs Medical Center, Louisville, KY, USA; Department of Biochemistry and Molecular Biology, University of Louisville, Louisville, KY, USA
* To whom correspondence should be addressed. E-mail: paul.epstein{at}louisville.edu.
Diabetic cardiomyopathy is a common complication leading to heightened risk of heart failure and death. In the present report, we performed proteomic analysis on total cardiac proteins from the OVE26 mouse model of Type I diabetes to identify protein changes that may contribute to diabetic cardiomyopathy. This analysis revealed that a surprising high proportion (twelve out of twenty) of the altered proteins that could be identified by mass spectrometry were of mitochondrial origin. All but one of these proteins were up-regulated by diabetes. Quantitative RT-PCR, performed for two of these proteins indicated that part of the up-regulation was attributed to increased messenger RNA levels. Morphological study of diabetic hearts showed significantly increased mitochondrial area and number, as well as focal regions with severe damage to mitochondria. Diabetic mitochondria also showed reduced respiratory control ratio (9.63 ± 0.20 vs. 6.13 ± 0.41, p<0.0001) apparently due to reduced state 3 rate, and diminished GSH level (5.5 ± 0.9 vs. 8.2 ± 2.5 µmol/mg protein, p<0.05), indicating impaired mitochondrial function and increased oxidative stress. Further examination revealed increased mitochondrial DNA (1.03 ± 0.18 vs 0.69 ± 0.13 relative copy number, p<0.001) and a tendency to higher protein yield in OVE26 cardiac mitochondria, as well as increased mRNA level for mitochondrial transcription factor A (Tfam) and two mitochondrial-encoded proteins. Taken together, these results show that mitochondria are a primary target in the diabetic heart, probably due to oxidative stress, and that this damage coincides with and may stimulate mitochondrial biogenesis.
This article has been cited by other articles:
|
|
 |
|
  E. D. Abel, S. E. Litwin, and G. Sweeney Cardiac Remodeling in Obesity Physiol Rev, April 1, 2008; 88(2): 389 - 419. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. G. Abraham and A. Kappas Pharmacological and Clinical Aspects of Heme Oxygenase Pharmacol. Rev., March 1, 2008; 60(1): 79 - 127. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Boudina, S. Sena, H. Theobald, X. Sheng, J. J. Wright, X. X. Hu, S. Aziz, J. I. Johnson, H. Bugger, V. G. Zaha, et al. Mitochondrial Energetics in the Heart in Obesity-Related Diabetes: Direct Evidence for Increased Uncoupled Respiration and Activation of Uncoupling Proteins Diabetes, October 1, 2007; 56(10): 2457 - 2466. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. P. Alcolea, I. Llado, F. J. Garcia-Palmer, and M. Gianotti Responses of mitochondrial biogenesis and function to maternal diabetes in rat embryo during the placentation period Am J Physiol Endocrinol Metab, September 1, 2007; 293(3): E636 - E644. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Boudina and E. D. Abel Diabetic Cardiomyopathy Revisited Circulation, June 26, 2007; 115(25): 3213 - 3223. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Hsueh, E. D. Abel, J. L. Breslow, N. Maeda, R. C. Davis, E. A. Fisher, H. Dansky, D. A. McClain, R. McIndoe, M. K. Wassef, et al. Recipes for Creating Animal Models of Diabetic Cardiovascular Disease Circ. Res., May 25, 2007; 100(10): 1415 - 1427. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Nisoli, E. Clementi, M. O. Carruba, and S. Moncada Defective Mitochondrial Biogenesis: A Hallmark of the High Cardiovascular Risk in the Metabolic Syndrome? Circ. Res., March 30, 2007; 100(6): 795 - 806. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. G. Duncan, J. L. Fong, D. M. Medeiros, B. N. Finck, and D. P. Kelly Insulin-Resistant Heart Exhibits a Mitochondrial Biogenic Response Driven by the Peroxisome Proliferator-Activated Receptor-{alpha}/PGC-1{alpha} Gene Regulatory Pathway Circulation, February 20, 2007; 115(7): 909 - 917. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H.-C. Lai, T.-J. Liu, C.-T. Ting, J.-Y. Yang, L. Huang, D. Wallace, P. Kaiser, and P. H. Wang Regulation of IGF-I receptor signaling in diabetic cardiac muscle: dysregulation of cytosolic and mitochondria HSP60 Am J Physiol Endocrinol Metab, January 1, 2007; 292(1): E292 - E297. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. An and B. Rodrigues Role of changes in cardiac metabolism in development of diabetic cardiomyopathy Am J Physiol Heart Circ Physiol, October 1, 2006; 291(4): H1489 - H1506. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Boudina and E. D. Abel Mitochondrial uncoupling: a key contributor to reduced cardiac efficiency in diabetes. Physiology, August 1, 2006; 21: 250 - 258. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. A. Di Noia, S. Van Driesche, F. Palmieri, L.-M. Yang, S. Quan, A. I. Goodman, and N. G. Abraham Heme Oxygenase-1 Enhances Renal Mitochondrial Transport Carriers and Cytochrome c Oxidase Activity in Experimental Diabetes J. Biol. Chem., June 9, 2006; 281(23): 15687 - 15693. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Shen, S. Zheng, N. S. Metreveli, and P. N. Epstein Protection of Cardiac Mitochondria by Overexpression of MnSOD Reduces Diabetic Cardiomyopathy Diabetes, March 1, 2006; 55(3): 798 - 805. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Ghosh, T. Pulinilkunnil, G. Yuen, G. Kewalramani, D. An, D. Qi, A. Abrahani, and B. Rodrigues Cardiomyocyte apoptosis induced by short-term diabetes requires mitochondrial GSH depletion Am J Physiol Heart Circ Physiol, August 1, 2005; 289(2): H768 - H776. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
