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Proteomic analysis of glomeruli from streptozotocin-induced diabetic rats

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Abstract

The kidney glomeruli are the sites of plasma filtration and production of primary urine. However, they are also the locus of kidney diseases, which progress to chronic renal failure. Glomeruli are a major target of injury in diabetic nephropathy (DN). The mechanisms by which glomerular filtration are regulated are poorly understood, and proteomic investigations of isolated glomeruli on the progressive development of DN in animal models have not been determined. To understand the molecular mechanism leading to DN, especially the glomerular injury mechanism, the differences in the glomerular proteomes of streptozotocin (STZ)-induced- and non-diabetic rats at six and 24 weeks were analyzed via two-dimensional electrophoresis (2-DE). To identify the progressive stages of DN, body weight, blood glucose, and proteinuria were measured periodically, and pathological changes were evaluated by periodic acid-Schiff staining. Magnetic beads were used to isolate glomeruli from kidneys and the glomerular proteomes of non-diabetic and STZ-induced diabetic rats were analyzed by 2-DE and nano-LC-ESI-MS/MS. Glutathione peroxidase 3, peroxiredoxin 2, and histone H2A were down-regulated, and annexin A3 was up-regulated, in the STZ-induced group compared with the controls. Glutathione peroxidase 3 and annexin A3, which might help elucidate the mechanism of DN, were verified by Western blotting. These proteins could potentially provide insight into the mechanism of glomerular injury in DN.

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References

  1. Hidai, H. (2000) Need for an incentive-based reimbursement policy toward quality care for dialysis patient management. Kidney Int. 58: 363–373.

    Article  CAS  Google Scholar 

  2. Ritz, E., I. Rychlik, F. Locatelli, and S. Halimi (1999) End-stage renal failure in type 2 diabetes: A medical catastrophe of worldwide dimensions. Am. J. Kidney Dis. 34: 795–808.

    Article  CAS  Google Scholar 

  3. Association, A. D. (2005) Standards of medical care in diabetes. Diabetes Care 28: 4–36.

    Article  Google Scholar 

  4. Hwang, P. T., O. D. Kwon, H. J. Kim, B. G. Kim, S. H. Kim, Y. W. Jang, P. K. Kim, G. Y. Han, and C. W. Kim (2012) Hyperglycemia decreases the expression of ATP synthase beta subunit and enolase 2 in glomerular epithelial cells. Tohoku J. Exp. Med. 231: 45–56.

    Article  Google Scholar 

  5. Schrier, R. W. (2007) Diseases of the kidney & urinary tract. 8th ed. Wolters Kluwer Health/Lippincott Williams & Wilkins, Philadelphia, USA.

    Google Scholar 

  6. Valderrabano, F., R. Jofre, and J. M. Lopez-Gomez (2001) Quality of life in end-stage renal disease patients. Am. J. Kidney Dis. 38: 443–464.

    Article  CAS  Google Scholar 

  7. Cooper, M. E. (2001) Interaction of metabolic and haemodynamic factors in mediating experimental diabetic nephropathy. Diabetol. 44: 1957–1972.

    Article  CAS  Google Scholar 

  8. Shields, A. T. and C. H. Chesnut (2001) Diagnosis of postmenopausal osteoporosis: Reviews in endocrine and metabolic disorders. Rev. Endocr. Metab. Disord. 2: 23–33.

    Article  CAS  Google Scholar 

  9. Aseer, K. R. and J. W. Yun (2013) Gender-dependent expression of pancreatic proteins in streptozotocin-induced diabetic rats. Biotechnol. Bioproc. Eng. 18: 1122–1134.

    Article  CAS  Google Scholar 

  10. Chaudhari, H. N. and J. W. Yun (2014) Gender-dimorphic regulation of liver proteins in Streptozotocin-induced diabetic rats. Biotechnol. Bioproc. Eng. 19: 93–107.

    Article  CAS  Google Scholar 

  11. Takemoto, M., N. Asker, H. Gerhardt, A. Lundkvist, B. R. Johansson, Y. Saito, and C. Betsholtz (2002) A new method for large scale isolation of kidney glomeruli from mice. Am. J. Pathol. 161: 799–805.

    Article  Google Scholar 

  12. Cho, E. H., M. R. Kim, H. J. Kim, D. Y. Lee, P. K. Kim, K. M. Choi, O. H. Ryu, and C. W. Kim (2007) The discovery of biomarkers for type 2 diabetic nephropathy by serum proteome analysis. Proteomics Clin. Appl. 1: 352–361.

    Article  CAS  Google Scholar 

  13. Kim, M. R., S. A. Yu, M. Y. Kim, K. M. Choi, and C. W. Kim (2014) Analysis of glycated serum proteins in type 2 diabetes patients with nephropathy. Biotechnol. Bioproc. Eng. 19: 83–92.

    Article  CAS  Google Scholar 

  14. Bradford, M. M. (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal. Biochem. 72: 248–254.

    Article  CAS  Google Scholar 

  15. So, E. J., H. J. Kim, and C. W. Kim (2008) Proteomic analysis of human proximal tubular cells exposed to high glucose concentrations. Proteomics Clin. Appl. 2: 1118–1126.

    Article  CAS  Google Scholar 

  16. Kim, H. J., M. R. Kim, E. J. So, and C. W. Kim (2007) Comparison of proteomes in various human plasma preparations by two-dimensional gel electrophoresis. J. Biochem. Biophys. Methods 70: 619–625.

    Article  CAS  Google Scholar 

  17. Kim, H. J., H. S. Yoo, P. K. Kim, M. R. Kim, H. W. Lee, and C. W. Kim (2011) Comparative analysis of serum proteomes of patients with cardiovascular disease. Clin. Biochem. 44: 178–184.

    Article  CAS  Google Scholar 

  18. Lee, E. K., H. Cho, and C. W. Kim (2011) Proteomic analysis of cancer stem cells in human prostate cancer cells. Biochem. Biophys. Res. Commun. 412: 279–285.

    Article  CAS  Google Scholar 

  19. Link, A. J., J. Eng, D. M. Schieltz, E. Carmack, G. J. Mize, D. R. Morris, B. M. Garvik, and J. R. Yates(1999) Direct analysis of protein complexes using mass spectrometry. Nat. Biotechnol. 17: 676–682.

    Article  CAS  Google Scholar 

  20. Tryggvason, S., M. Nukui, A. Oddsson, K. Tryggvason, and H. Jornvall (2007) Glomerulus proteome analysis with two-dimensional gel electrophoresis and mass spectrometry. Cell Mol. Life Sci. 64: 3317–3335.

    Article  CAS  Google Scholar 

  21. Blutke, A., C. Block, F. Berendt, N. Herbach, E. Kemter, K. Amann, T. Frohlich, G. J. Arnold, and R. Wanke (2011) Differential glomerular proteome analysis of two murine nephropathy models at onset of albuminuria. Proteom Clin. Appl. 5: 375–381.

    Article  CAS  Google Scholar 

  22. Zhang, Y., Y. Yoshida, B. Xu, S. Magdeldin, H. Fujinaka, Z. Liu, M. Miyamoto, E. Yaoita, and T. Yamamoto (2011) Comparison of human glomerulus proteomic profiles obtained from low quantities of samples by different mass spectrometry with the comprehensive database. Proteome Sci. 9: 47.

    Article  CAS  Google Scholar 

  23. Yoshida, Y., K. Miyazaki, J. Kamiie, M. Sato, S. Okuizumi, A. Kenmochi, K. Kamijo, T. Nabetani, A. Tsugita, B. Xu, Y. Zhang, E. Yaoita, T. Osawa, and T. Yamamoto (2005) Two-dimensional electrophoretic profiling of normal human kidney glomerulus proteome and construction of an extensible markup language (XML)-based database. Proteomics 5: 1083–1096.

    Article  CAS  Google Scholar 

  24. Cui, Z., Y. Yoshida, B. Xu, Y. Zhang, M. Nameta, S. Magdeldin, T. Makiguchi, T. Ikoma, H. Fujinaka, E. Yaoita, and T. Yamamoto (2013) Profiling and annotation of human kidney glomerulus proteome. Proteome Sci. 11: 13.

    Article  CAS  Google Scholar 

  25. Kim, H. J., E. H. Cho, J. H. Yoo, P. K. Kim, J. S. Shin, M. R. Kim, and C. W. Kim (2007) Proteome analysis of serum from type 2 diabetics with nephropathy. J. Proteome Res. 6: 735–743.

    Article  CAS  Google Scholar 

  26. Brunskill, E. W. and S. S. Potter (2012) Changes in the gene expression programs of renal mesangial cells during diabetic nephropathy. BMC Nephrol. 13: 70.

    Article  Google Scholar 

  27. Yoshimura, S., K. Watanabe, H. Suemizu, T. Onozawa, J. Mizoguchi, K. Tsuda, H. Hatta, and T. Moriuchi (1991) Tissue specific expression of the plasma glutathione peroxidase gene in rat kidney. J. Biochem. 109: 918–923.

    CAS  Google Scholar 

  28. Maser, R. L., B. S. Magenheimer, and J. P. Calvet (1994) Mouse plasma glutathione peroxidase. cDNA sequence analysis and renal proximal tubular expression and secretion. J. Biol. Chem. 269: 27066–27073.

    CAS  Google Scholar 

  29. Schwaab, V., J. Faure, J. P. Dufaure, and J. R. Drevet (1998) GPx3: The plasma-type glutathione peroxidase is expressed under androgenic control in the mouse epididymis and vas deferens. Mol. Reprod. Dev. 51: 362–372.

    Article  CAS  Google Scholar 

  30. Wilson, K. H., S. E. Eckenrode, Q. Z. Li, Q. G. Ruan, P. Yang, J. D. Shi, A. Davoodi-Semiromi, R. A. McIndoe, B. P. Croker, and J. X. She (2003) Microarray analysis of gene expression in the kidneys of new- and post-onset diabetic NOD mice. Diabetes 52: 2151–2159.

    Article  CAS  Google Scholar 

  31. de Haan, J. B., N. Stefanovic, D. Nikolic-Paterson, L. L. Scurr, K. D. Croft, T. A. Mori, P. Hertzog, I. Kola, R. C. Atkins, and G. H. Tesch (2005) Kidney expression of glutathione peroxidase-1 is not protective against streptozotocin-induced diabetic nephropathy. Am. J. Physiol. Renal. Physiol. 289: 544–551.

    Article  Google Scholar 

  32. Reddi, A. S. and J. S. Bollineni (2001) Selenium-deficient diet induces renal oxidative stress and injury via TGF-beta1 in normal and diabetic rats. Kidney Int. 59: 1342–1353.

    Article  CAS  Google Scholar 

  33. Kahler, W., B. Kuklinski, C. Ruhlmann, and C. Plotz (1993) Diabetes mellitus—a free radical-associated disease. Results of adjuvant antioxidant supplementation. Z Gesamte Inn. Med. 48: 223–232.

    CAS  Google Scholar 

  34. Gerke, V., C. E. Creutz, and S. E. Moss (2005) Annexins: Linking Ca2+ signalling to membrane dynamics. Nat. Rev. Mol. Cell Biol. 6: 449–461.

    Article  CAS  Google Scholar 

  35. Park, J. E., D. H. Lee, J. A. Lee, S. G. Park, N. S. Kim, B. C. Park, and S. Cho (2005) Annexin A3 is a potential angiogenic mediator. Biochem. Biophys. Res. Commun. 337: 1283–1287.

    Article  CAS  Google Scholar 

  36. Kim, N. H., D. R. Cha, Y. S. Kang, S. Y. Han, Y. H. Jee, K. H. Han, J. Y. Han, and Y. S. Kim (2004) Vascular endothelial growth factor is increased during early stage of diabetic nephropathy in type II diabetic rats. J. Endocrinol. 183: 183–194.

    Article  Google Scholar 

  37. Flyvbjerg, A., F. Dagnaes-Hansen, A. S. De Vriese, B. F. Schrijvers, R. G. Tilton, and R. Rasch (2002) Amelioration of longterm renal changes in obese type 2 diabetic mice by a neutralizing vascular endothelial growth factor antibody. Diabetes 51: 3090–3094.

    Article  CAS  Google Scholar 

  38. Hovind, P., L. Tarnow, P. B. Oestergaard, and H. H. Parving (2000) Elevated vascular endothelial growth factor in type 1 diabetic patients with diabetic nephropathy. Kidney Int. Suppl. 75: 56–61.

    Article  Google Scholar 

  39. Chae, H. Z., I. H. Kim, K. Kim, and S. G. Rhee (1993) Cloning, sequencing, and mutation of thiol-specific antioxidant gene of Saccharomyces cerevisiae. J. Biol. Chem. 268: 16815–16821.

    CAS  Google Scholar 

  40. Soini, Y., J. P. Kallio, P. Hirvikoski, H. Helin, P. Kellokumpu-Lehtinen, S. W. Kang, T. L. Tammela, M. Peltoniemi, P. M. Martikainen, and V. L. Kinnula (2006) Oxidative/nitrosative stress and peroxiredoxin 2 are associated with grade and prognosis of human renal carcinoma. APMIS. 114: 329–337.

    Article  CAS  Google Scholar 

  41. Rao, P. V., A. P. Reddy, X. Lu, S. Dasari, A. Krishnaprasad, E. Biggs, C. T. Roberts, and S. R. Nagalla (2009) Proteomic identification of salivary biomarkers of type-2 diabetes. J. Proteome Res. 8: 239–245.

    Article  CAS  Google Scholar 

  42. Lee, S. C., Y. P. Na, and J. B. Lee (2003) Expression of peroxiredoxin II in vascular tumors of the skin: A novel vascular marker of endothelial cells. J. Am. Acad. Dermatol. 49: 487–491.

    Article  Google Scholar 

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Kim, HJ., Kwon, OD., Kim, SH. et al. Proteomic analysis of glomeruli from streptozotocin-induced diabetic rats. Biotechnol Bioproc E 19, 650–659 (2014). https://doi.org/10.1007/s12257-014-0184-4

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  • DOI: https://doi.org/10.1007/s12257-014-0184-4

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