Table of Contents
ISRN Endocrinology
Volume 2012, Article ID 162802, 10 pages
http://dx.doi.org/10.5402/2012/162802
Research Article

C-Peptide Reduces Mitochondrial Superoxide Generation by Restoring Complex I Activity in High Glucose-Exposed Renal Microvascular Endothelial Cells

1Department of Physiology and Pharmacology, West Virginia University School of Medicine, P.O. Box 9105, Morgantown, WV 26506, USA
2Center for Cardiovascular and Respiratory Sciences, West Virginia University School of Medicine, Morgantown, WV 26506, USA
3Division of Exercise Physiology, West Virginia University School of Medicine, Morgantown, WV 26506, USA

Received 14 March 2012; Accepted 10 April 2012

Academic Editors: O. Giampietro, J. Pachucki, and H. Tamemoto

Copyright © 2012 Himani Vejandla et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. P. A. McCullough, G. L. Bakris, W. F. Owen, P. S. Klassen, and R. M. Califf, “Slowing the progression of diabetic nephropathy and its cardiovascular consequences,” American Heart Journal, vol. 148, no. 2, pp. 243–251, 2004. View at Publisher · View at Google Scholar · View at Scopus
  2. R. A. Nugent, S. F. Fathima, A. B. Feigl, and D. Chyung, “The burden of chronic kidney disease on developing nations: a 21st century challenge in global health,” Nephron, vol. 118, no. 3, pp. c269–c276, 2011. View at Publisher · View at Google Scholar · View at Scopus
  3. C. E. Mogensen, “Preventing end-stage renal disease,” Diabetic Medicine, vol. 15, no. 4, pp. S51–S56, 1998. View at Google Scholar · View at Scopus
  4. C. E. Mogensen, “The kidney in diabetes: how to control renal and related cardiovascular complications,” American Journal of Kidney Diseases, vol. 37, no. 1, supplement 2, pp. S2–S6, 2001. View at Google Scholar · View at Scopus
  5. J. B. McGill, “Improving microvascular outcomes in patients with diabetes through management of hypertension,” Postgraduate Medicine, vol. 121, no. 2, pp. 89–101, 2009. View at Publisher · View at Google Scholar · View at Scopus
  6. M. Brownlee, “Biochemistry and molecular cell biology of diabetic complications,” Nature, vol. 414, no. 6865, pp. 813–820, 2001. View at Publisher · View at Google Scholar · View at Scopus
  7. M. Brownlee, “The pathobiology of diabetic complications: a unifying mechanism,” Diabetes, vol. 54, no. 6, pp. 1615–1625, 2005. View at Publisher · View at Google Scholar · View at Scopus
  8. Y. Du, C. M. Miller, and T. S. Kern, “Hyperglycemia increases mitochondrial superoxide in retina and retinal cells,” Free Radical Biology and Medicine, vol. 35, no. 11, pp. 1491–1499, 2003. View at Publisher · View at Google Scholar · View at Scopus
  9. B. D. Fink, K. J. Reszka, J. A. Herlein, M. M. Mathahs, and W. I. Sivitz, “Respiratory uncoupling by UCP1 and UCP2 and superoxide generation in endothelial cell mitochondria,” American Journal of Physiology, vol. 288, no. 1, pp. E71–E79, 2005. View at Publisher · View at Google Scholar · View at Scopus
  10. W. F. Graier, K. Posch, E. Fleischhacker, T. C. Wascher, and G. M. Kostner, “Increased superoxide anion formation in endothelial cells during hyperglycemia: an adaptive response or initial step of vascular dysfunction?” Diabetes Research and Clinical Practice, vol. 45, no. 2-3, pp. 153–160, 1999. View at Publisher · View at Google Scholar · View at Scopus
  11. C. Quijano, L. Castro, G. Peluffo, V. Valez, and R. Radi, “Enhanced mitochondrial superoxide in hyperglycemic endothelial cells: direct measurements and formation of hydrogen peroxide and peroxynitrite,” American Journal of Physiology, vol. 293, no. 6, pp. H3404–H3414, 2007. View at Publisher · View at Google Scholar · View at Scopus
  12. H. Bugger, S. Boudina, X. X. Hu et al., “Type 1 diabetic akita mouse hearts are insulin sensitive but manifest structurally abnormal mitochondria that remain coupled despite increased uncoupling protein 3,” Diabetes, vol. 57, no. 11, pp. 2924–2932, 2008. View at Publisher · View at Google Scholar · View at Scopus
  13. J. A. Herlein, B. D. Fink, Y. O'Malley, and W. I. Sivitz, “Superoxide and respiratory coupling in mitochondria of insulin-deficient diabetic rats,” Endocrinology, vol. 150, no. 1, pp. 46–55, 2009. View at Publisher · View at Google Scholar · View at Scopus
  14. C. M. Palmeira, A. P. Rolo, J. Berthiaume, J. A. Bjork, and K. B. Wallace, “Hyperglycemia decreases mitochondrial function: the regulatory role of mitochondrial biogenesis,” Toxicology and Applied Pharmacology, vol. 225, no. 2, pp. 214–220, 2007. View at Publisher · View at Google Scholar · View at Scopus
  15. W. I. Sivitz and M. A. Yorek, “Mitochondrial dysfunction in diabetes: from molecular mechanisms to functional significance and therapeutic opportunities,” Antioxidants and Redox Signaling, vol. 12, no. 4, pp. 537–577, 2010. View at Publisher · View at Google Scholar · View at Scopus
  16. D. Esterházy, M. S. King, G. Yakovlev, and J. Hirst, “Production of reactive oxygen species by complex I (NADH:ubiquinone oxidoreductase) from Escherichia coli and comparison to the enzyme from mitochondria,” Biochemistry, vol. 47, no. 12, pp. 3964–3971, 2008. View at Publisher · View at Google Scholar · View at Scopus
  17. A. J. Lambert and M. D. Brand, “Inhibitors of the quinone-binding site allow rapid superoxide production from mitochondrial NADH:ubiquinone oxidoreductase (complex I),” The Journal of Biological Chemistry, vol. 279, no. 38, pp. 39414–39420, 2004. View at Publisher · View at Google Scholar · View at Scopus
  18. M. L. Genova, M. M. Pich, A. Bernacchia et al., “The mitochondrial production of reactive oxygen species in relation to aging and pathology,” Annals of the New York Academy of Sciences, vol. 1011, pp. 86–100, 2004. View at Publisher · View at Google Scholar · View at Scopus
  19. M. L. Genova, B. Ventura, G. Giuliano et al., “The site of production of superoxide radical in mitochondrial Complex I is not a bound ubisemiquinone but presumably iron-sulfur cluster N2,” FEBS Letters, vol. 505, no. 3, pp. 364–368, 2001. View at Publisher · View at Google Scholar · View at Scopus
  20. M. P. Murphy, “How mitochondria produce reactive oxygen species,” Biochemical Journal, vol. 417, no. 1, pp. 1–13, 2009. View at Publisher · View at Google Scholar · View at Scopus
  21. D. F. Steiner, “On the role of the proinsulin C-peptide,” Diabetes, vol. 27, no. 1, pp. 145–148, 1978. View at Google Scholar · View at Scopus
  22. B. L. Johansson, K. Borg, E. Fernqvist-Forbes, A. Kernell, T. Odergren, and J. Wahren, “Beneficial effects of C-peptide on incipient nephropathy and neuropathy in patients with Type 1 diabetes mellitus,” Diabetic Medicine, vol. 17, no. 3, pp. 181–189, 2000. View at Publisher · View at Google Scholar · View at Scopus
  23. B. L. Johansson, S. Sjoberg, and J. Wahren, “The influence of human C-peptide on renal function and glucose utilization in Type 1 (insulin-dependent) diabetic patients,” Diabetologia, vol. 35, no. 2, pp. 121–128, 1992. View at Google Scholar · View at Scopus
  24. D. Y. Huang, K. Richter, A. Breidenbach, and V. Vallon, “Human C-peptide acutely lowers glomerular hyperfiltration and proteinuria in diabetic rats: a dose-response study,” Naunyn-Schmiedeberg's Archives of Pharmacology, vol. 365, no. 1, pp. 67–73, 2002. View at Publisher · View at Google Scholar · View at Scopus
  25. L. Nordquist, R. Brown, A. Fasching, P. Persson, and F. Palm, “Proinsulin C-peptide reduces diabetes-induced glomerular hyperfiltration via efferent arteriole dilation and inhibition of tubular sodium reabsorption,” American Journal of Physiology, vol. 297, no. 5, pp. F1265–F1272, 2009. View at Publisher · View at Google Scholar · View at Scopus
  26. L. Nordquist, Y. L. En, M. Sjöquist, A. Patzak, and A. E. G. Persson, “Proinsulin C-peptide constricts glomerular afferent arterioles in diabetic mice. A potential renoprotective mechanism,” American Journal of Physiology, vol. 294, no. 3, pp. R835–R841, 2008. View at Publisher · View at Google Scholar · View at Scopus
  27. B. Samnegård, S. H. Jacobson, G. Jaremko, B. L. Johansson, and M. Sjöquist, “Effects of C-peptide on glomerular and renal size and renal function in diabetic rats,” Kidney International, vol. 60, no. 4, pp. 1258–1265, 2001. View at Publisher · View at Google Scholar · View at Scopus
  28. B. Samnegård, S. H. Jacobson, G. Jaremko et al., “C-peptide prevents glomerular hypertrophy and mesangial matrix expansion in diabetic rats,” Nephrology Dialysis Transplantation, vol. 20, no. 3, pp. 532–538, 2005. View at Publisher · View at Google Scholar · View at Scopus
  29. N. M. Al-Rasheed, F. Meakin, E. L. Royal et al., “Potent activation of multiple signalling pathways by C-peptide in opossum kidney proximal tubular cells,” Diabetologia, vol. 47, no. 6, pp. 987–997, 2004. View at Google Scholar · View at Scopus
  30. J. Shafqat, L. Juntti-Berggren, Z. Zhong et al., “Proinsulin C-peptide and its analogues induce intracellular Ca2+ increases in human renal tubular cells,” Cellular and Molecular Life Sciences, vol. 59, no. 7, pp. 1185–1189, 2002. View at Publisher · View at Google Scholar · View at Scopus
  31. Z. Zhong, A. Davidescu, I. Ehrén et al., “C-peptide stimulates ERK1/2 and JNK MAP kinases via activation of protein kinase C in human renal tubular cells,” Diabetologia, vol. 48, no. 1, pp. 187–197, 2005. View at Publisher · View at Google Scholar · View at Scopus
  32. R. R. Langley, K. M. Ramirez, R. Z. Tsan, M. Van Arsdall, M. B. Nilsson, and I. J. Fidler, “Tissue-specific microvascular endothelial cell lines from H-2Kb-tsA58 mice for studies of angiogenesis and metastasis,” Cancer Research, vol. 63, no. 11, pp. 2971–2976, 2003. View at Google Scholar · View at Scopus
  33. D. L. Horwitz, J. I. Starr, and M. E. Mako, “Proinsulin, insulin and C-peptide concentrations in human portal and peripheral blood,” Journal of Clinical Investigation, vol. 55, no. 6, pp. 1278–1283, 1975. View at Google Scholar · View at Scopus
  34. T. Wallerath, T. Kunt, T. Forst et al., “Stimulation of endothelial nitric oxide synthase by proinsulin C-peptide,” Nitric Oxide, vol. 9, no. 2, pp. 95–102, 2003. View at Publisher · View at Google Scholar · View at Scopus
  35. E. R. Dabkowski, C. L. Williamson, and J. M. Hollander, “Mitochondria-specific transgenic overexpression of phospholipid hydroperoxide glutathione peroxidase (GPx4) attenuates ischemia/reperfusion-associated cardiac dysfunction,” Free Radical Biology and Medicine, vol. 45, no. 6, pp. 855–865, 2008. View at Publisher · View at Google Scholar · View at Scopus
  36. M. Friederich, P. Hansell, and F. Palm, “Diabetes, oxidative stress, nitric oxide and mitochondria function,” Current Diabetes Reviews, vol. 5, no. 2, pp. 120–144, 2009. View at Publisher · View at Google Scholar · View at Scopus
  37. S. Munusamy and L. A. MacMillan-Crow, “Mitochondrial superoxide plays a crucial role in the development of mitochondrial dysfunction during high glucose exposure in rat renal proximal tubular cells,” Free Radical Biology and Medicine, vol. 46, no. 8, pp. 1149–1157, 2009. View at Publisher · View at Google Scholar · View at Scopus
  38. P. Mukhopadhyay, M. Rajesh, K. Yoshihiro, G. Haskó, and P. Pacher, “Simple quantitative detection of mitochondrial superoxide production in live cells,” Biochemical and Biophysical Research Communications, vol. 358, no. 1, pp. 203–208, 2007. View at Publisher · View at Google Scholar · View at Scopus
  39. I. A. Trounce, Y. L. Kim, A. S. Jun, and D. C. Wallace, “Assessment of mitochondrial oxidative phosphorylation in patient muscle biopsies, lymphoblasts, and transmitochondrial cell lines,” Methods in Enzymology, vol. 264, pp. 484–509, 1996. View at Google Scholar · View at Scopus
  40. X. Shen, S. Zheng, V. Thongboonkerd et al., “Cardiac mitochondrial damage and biogenesis in a chronic model of type 1 diabetes,” American Journal of Physiology, vol. 287, no. 5, pp. E896–E905, 2004. View at Publisher · View at Google Scholar · View at Scopus
  41. S. S. Korshunov, V. P. Skulachev, and A. A. Starkov, “High protonic potential actuates a mechanism of production of reactive oxygen species in mitochondria,” FEBS Letters, vol. 416, no. 1, pp. 15–18, 1997. View at Publisher · View at Google Scholar · View at Scopus
  42. A. P. Rolo and C. M. Palmeira, “Diabetes and mitochondrial function: role of hyperglycemia and oxidative stress,” Toxicology and Applied Pharmacology, vol. 212, no. 2, pp. 167–178, 2006. View at Publisher · View at Google Scholar · View at Scopus
  43. M. Kanwar, P. S. Chan, T. S. Kern, and R. A. Kowluru, “Oxidative damage in the retinal mitochondria of diabetic mice: possible protection by superoxide dismutase,” Investigative Ophthalmology and Visual Science, vol. 48, no. 8, pp. 3805–3811, 2007. View at Publisher · View at Google Scholar · View at Scopus
  44. M. D. Brand, C. Affourtit, T. C. Esteves et al., “Mitochondrial superoxide: production, biological effects, and activation of uncoupling proteins,” Free Radical Biology and Medicine, vol. 37, no. 6, pp. 755–767, 2004. View at Publisher · View at Google Scholar · View at Scopus
  45. K. Green, M. D. Brand, and M. P. Murphy, “Prevention of mitochondrial oxidative damage as a therapeutic strategy in diabetes,” Diabetes, vol. 53, supplement 1, pp. S110–S118, 2004. View at Google Scholar · View at Scopus
  46. T. R. Hurd, R. Requejo, A. Filipovska et al., “Complex I within oxidatively stressed bovine heart mitochondria is glutathionylated on Cys-531 and Cys-704 of the 75-kDa subunit: potential role of Cys residues in decreasing oxidative damage,” Journal of Biological Chemistry, vol. 283, no. 36, pp. 24801–24815, 2008. View at Publisher · View at Google Scholar · View at Scopus
  47. S. M. Beer, E. R. Taylor, S. E. Brown et al., “Glutaredoxin 2 catalyzes the reversible oxidation and glutathionylation of mitochondrial membrane thiol proteins: implications for mitochondrial redox regulation and antioxidant defense,” Journal of Biological Chemistry, vol. 279, no. 46, pp. 47939–47951, 2004. View at Publisher · View at Google Scholar · View at Scopus
  48. T. R. Hurd, N. J. Costa, C. C. Dahm et al., “Glutathionylation of mitochondrial proteins,” Antioxidants and Redox Signaling, vol. 7, no. 7-8, pp. 999–1010, 2005. View at Publisher · View at Google Scholar · View at Scopus
  49. T. Kitamura, K. Kimura, B. D. Jung et al., “Proinsulin C-peptide rapidly stimulates mitogen-activated protein kinases in swiss 3T3 fibroblasts: requirement of protein kinase C, phosphoinositide 3-kinase and pertussis toxin-sensitive G-protein,” Biochemical Journal, vol. 355, no. 1, pp. 123–129, 2001. View at Publisher · View at Google Scholar · View at Scopus
  50. T. Kitamura, K. Kimura, B. D. Jung et al., “Proinsulin C-peptide activates cAMP response element-binding proteins through the p38 mitogen-activated protein kinase pathway in mouse lung capillary endothelial cells,” Biochemical Journal, vol. 366, no. 3, pp. 737–744, 2002. View at Publisher · View at Google Scholar · View at Scopus
  51. T. Kitamura, K. Kimura, K. Makondo et al., “Proinsulin C-peptide increases nitric oxide production by enhancing mitogen-activated protein-kinase-dependent transcription of endothelial nitric oxide synthase in aortic endothelial cells of Wistar rats,” Diabetologia, vol. 46, no. 12, pp. 1698–1705, 2003. View at Publisher · View at Google Scholar · View at Scopus
  52. G. Grunberger, X. Qiang, Z. Li et al., “Molecular basis for the insulinomimetic effects of C-peptide,” Diabetologia, vol. 44, no. 10, pp. 1247–1257, 2001. View at Publisher · View at Google Scholar · View at Scopus
  53. Z. G. Li, X. Qiang, A. A. F. Sima, and G. Grunberger, “C-peptide attenuates protein tyrosine phosphatase activity and enhances glycogen synthesis in l6 myoblasts,” Biochemical and Biophysical Research Communications, vol. 280, no. 3, pp. 615–619, 2001. View at Publisher · View at Google Scholar · View at Scopus
  54. Z. Zhong, O. Kotova, A. Davidescu et al., “C-peptide stimulates Na+,K+-ATPase via activation of ERK1/2 MAP kinases in human renal tubular cells,” Cellular and Molecular Life Sciences, vol. 61, no. 21, pp. 2782–2790, 2004. View at Publisher · View at Google Scholar · View at Scopus
  55. R. Seger, T. Hanoch, R. Rosenberg et al., “The ERK signaling cascade inhibits gonadotropin-stimulated steroidogenesis,” Journal of Biological Chemistry, vol. 276, no. 17, pp. 13957–13964, 2001. View at Google Scholar · View at Scopus
  56. M. M. Monick, L. S. Powers, C. W. Barrett et al., “Constitutive ERK MAPK activity regulates macrophage ATP production and mitochondrial integrity,” Journal of Immunology, vol. 180, no. 11, pp. 7485–7496, 2008. View at Google Scholar · View at Scopus