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Proteasome activity in experimental diabetes

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Central European Journal of Biology

Abstract

Numerous studies have indicated that oxidative stress contributes to the development and progression of diabetes and other related complications. Since the ubiquitin-proteasome pathway is involved in degradation of oxidized proteins, it is to be expected that alterations in proteasome-dependent proteolysis accompany diabetes. This paper focuses on the role of the proteasome in alloxan-induced experimental diabetes. The changes in proteasomal activity and oxidative stress indices (protein oxidation and lipid peroxidation) were evaluated. The obtained results revealed increased protein oxidation and lipid peroxidation, as well as alterations in proteasomal activities in diabetic rats. Our data indicates a significant decrease in chymotryptic-like activity; increased tryptic-like activity; and unchanged post-glutamyl peptide hydrolytic-like activity. These findings suggest the presence of oxidative stress in diabetes that appears to result in changes to the ubiquitin-proteasome pathway.

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References

  1. P. Brooks, G. Fuertes, R.Z. Murray, S. Bose, E. Knecht, M.C. Rechsteiner, K.B. Hendil, K. Tanaka, J. Dyson and J. Rivett: “Subcellular localization of proteasomes and their regulatory complexes in mammalian cells”, Biochem. J., Vol. 346, (2000), pp. 155–161.

    Article  PubMed  CAS  Google Scholar 

  2. C. Wojcik and G.N. DeMartino: “Intracellular localization of proteasomes”, Int. J. Biochem. Cell Biol., Vol. 35, (2003), pp. 579–589.

    Article  PubMed  CAS  Google Scholar 

  3. J. Lowe, D. Stock, B. Jap, P. Zwickl, W. Baumeister and R. Huber: “Crystal structure of the 20S proteasome from the archaeon T. acidophilum at 3.4 A resolution”, Science, Vol. 268, (1995), pp. 533–539.

    PubMed  CAS  Google Scholar 

  4. G. Puhler, S. Weinkauf, L. Bachmann, S. Muller, A. Engel, R. Hegerl and W. Baumeister: “Subunit stoichiometry and three-dimensional arrangement in proteasomes from Thermoplasma acidophilum”, EMBO J., Vol. 11, (1992), pp. 1607–1616.

    PubMed  CAS  Google Scholar 

  5. M. Orlowski, C. Cardozo and C. Michaud: “Evidence for the presence of five distinct proteolytic components in the pituitary multicatalytic proteinase complex. Properties of two components cleaving bonds on the carboxyl side of branched chain and small neutral amino acids”, Biochem., Vol. 32, (1993), pp. 1563–1572.

    Article  CAS  Google Scholar 

  6. H.P. Schmid and J. Briand: “Proteasomes and related complexes”, Mol. Biol. Reports, Vol. 24, (1997), pp. 1–138.

    CAS  Google Scholar 

  7. C. Naujokat and S. Hoffmann: “Role and function of the 26S proteasome in proliferation and apoptosis”, Lab Invest., Vol. 82, (2002), pp. 965–980.

    PubMed  CAS  Google Scholar 

  8. E. Reinstein: “Immunologic aspects of protein degradation by the ubiquitin-proteasome system”, Isr. Med. Assoc. J., Vol. 6, (2004), pp. 420–424.

    PubMed  CAS  Google Scholar 

  9. S.P. Wolff and R.T. Dean: “Glucose autoxidation and protein modification. The potential role of’ autoxidative glycosylation’ in diabetes”, Biochem. J., Vol. 245, (1987), pp. 243–250.

    PubMed  CAS  Google Scholar 

  10. M. Brownlee, A. Cerami and H. Vlassara: “Advanced products of nonenzymatic glycosylation and the pathogenesis of diabetic vascular disease”, Diabetes Metab. Rev., Vol. 4, (1988), pp. 437–451.

    Article  PubMed  CAS  Google Scholar 

  11. T. Inoguchi, P. Li, F. Umeda, H.Y. Yu, M. Kakimoto, M. Imamura, T. Aoki, T. Etoh, T. Hashimoto, M. Naruse, H. Sano, H. Utsumi and H. Nawata: “High glucose level and free fatty acid stimulate reactive oxygen species production through protein kinase C-dependent activation of NAD(P)H oxidase in cultured vascular cells”, Diabetes, Vol. 49, (2000), pp. 1939–1945.

    PubMed  CAS  Google Scholar 

  12. F. Cosentino, K. Hishikawa, Z.S. Katusic and T.F. Luscher: “High glucose increases nitric oxide synthase expression and superoxide anion generation in human aortic endothelial cells”, Circulation, Vol. 96, (1997), pp. 25–28.

    PubMed  CAS  Google Scholar 

  13. M.C. Desco, M. Asensi, R. Marquez, J. Martinez-Valls, M. Vento, F.V. Pallardo, J. Sastre and J. Vina: “Xanthine oxidase is involved in free radical production in type 1 diabetes: protection by allopurinol”, Diabetes, Vol. 51, (2002), pp. 1118–1124.

    PubMed  CAS  Google Scholar 

  14. L.W. Oberley: “Free radicals and diabetes”, Free Radic. Biol. Med., Vol. 5, (1988), pp. 113–124.

    Article  PubMed  CAS  Google Scholar 

  15. E.R. Stadtman and C.N. Oliver: “Metal-catalyzed oxidation of proteins. Physiological consequences”, J. Biol. Chem., Vol. 266, (1991), pp. 2005–2008.

    PubMed  CAS  Google Scholar 

  16. T. Miyata, R. Inagi, K. Asahi, Y. Yamada, K. Horie, H. Sakai, K. Uchida and K. Kurokawa: “Generation of protein carbonyls by glycoxidation and lipoxidation reactions with autoxidation products of ascorbic acid and polyunsaturated fatty acids”, FEBS Lett., Vol. 437, (1998), pp. 24–28.

    Article  PubMed  CAS  Google Scholar 

  17. T. Grune, T. Reinheckel, M. Joshi and K.J. Davies: “Proteolysis in cultured liver epithelial cells during oxidative stress. Role of the multicatalytic proteinase complex, proteasome”, J. Biol. Chem., Vol. 270, (1995), pp. 2344–2351.

    Article  PubMed  CAS  Google Scholar 

  18. T. Reinheckel, N. Sitte, O. Ullrich, U. Kuckelkorn, K.J. Davies and T. Grune: “Comparative resistance of the 20S and 26S proteasome to oxidative stress”, Biochem. J., Vol. 335, (1998), pp. 637–642.

    PubMed  CAS  Google Scholar 

  19. O.H. Lowry, N.J. Rosebrough, A.L. Farr and R.J. Randall: “Protein measurement with the Folin phenol reagent”, J. Biol. Chem., Vol. 193, (1951), pp. 265–275.

    PubMed  CAS  Google Scholar 

  20. F.E. Hunter, Jr., J.M. Gebicki, P.E. Hoffsten, J. Weinstein and A. Scott: “Swelling and lysis of rat liver mitochondria induced by ferrous ions”, J. Biol. Chem., Vol. 238, (1963), pp. 828–835.

    PubMed  CAS  Google Scholar 

  21. M.J. Whitekus, N. Li, M. Zhang, M. Wang, M.A. Horwitz, S.K. Nelson, L.D. Horwitz, N. Brechun, D. Diaz-Sanchez and A.E. Nel: “Thiol antioxidants inhibit the adjuvant effects of aerosolized diesel exhaust particles in a murine model for ovalbumin sensitization”, J. Immunol., Vol. 168, (2002), pp. 2560–2567.

    PubMed  CAS  Google Scholar 

  22. A.L. Bulteau, K.C. Lundberg, K.M. Humphries, H.A. Sadek, P.A. Szweda, B. Friguet and L.I. Szweda: “Oxidative modification and inactivation of the proteasome during coronary occlusion/reperfusion”, J. Biol. Chem., Vol. 276, (2001), pp. 30057–30063.

    Article  PubMed  CAS  Google Scholar 

  23. D. Voges, P. Zwickl and W. Baumeister: “The 26S proteasome: a molecular machine designed for controlled proteolysis”, Annu. Rev. Biochem., Vol. 68, (1999), pp. 1015–1068.

    Article  PubMed  CAS  Google Scholar 

  24. R. Shringarpure, T. Grune and K.J. Davies: “Protein oxidation and 20S proteasome-dependent proteolysis in mammalian cells”, Cell Mol. Life Sci., Vol. 58, (2001), pp. 1442–1450.

    Article  PubMed  CAS  Google Scholar 

  25. T. Grune, T. Reinheckel, M. Joshi and K.J. Davies: “Proteolysis in cultured liver epithelial cells during oxidative stress. Role of the multicatalytic proteinase complex, proteasome”, J. Biol. Chem., Vol. 270, (1995), pp. 2344–2351.

    Article  PubMed  CAS  Google Scholar 

  26. S. Merforth, L. Kuehn, A. Osmers and B. Dahlmann: “Alteration of 20S proteasome-subtypes and proteasome activator PA28 in skeletal muscle of rat after induction of diabetes mellitus”, Int. J. Biochem. Cell Biol., Vol. 35, (2003), pp. 740–748.

    Article  PubMed  CAS  Google Scholar 

  27. A.J. Ashford and V.M. Pain: “Effect of diabetes on the rates of synthesis and degradation of ribosomes in rat muscle and liver in vivo”, J. Biol. Chem., Vol. 261, (1986), pp. 4059–4065.

    PubMed  CAS  Google Scholar 

  28. O.L. Smith, C.Y. Wong and R.A. Gelfand: “Skeletal muscle proteolysis in rats with acute streptozocin-induced diabetes”, Diabetes, Vol. 38, (1989), pp. 1117–1122.

    PubMed  CAS  Google Scholar 

  29. H.A. Runnels, W.A. Watkins and J.J. Monaco: “LMP2 expression and proteasome activity in NOD mice”, Nat. Med., Vol. 6, (2000), pp. 1064–1065.

    PubMed  CAS  Google Scholar 

  30. T. Hayashi and D. Faustman: “NOD mice are defective in proteasome production and activation of NF-kappaB”, Mol. Cell. Biol., Vol. 19, (1999), pp. 8646–8659.

    PubMed  CAS  Google Scholar 

  31. S.J. Rhee, Y.C. Jeong and J.H. Choi: “Effects of vitamin E on phospholipase A2 activity and oxidative damage to the liver in streptozotocin-induced diabetic rats”, Ann. Nutr. Metab, Vol. 49, (2005), pp. 392–396.

    Article  PubMed  CAS  Google Scholar 

  32. Y.Y. Jang, J.H. Song, Y.K. Shin, E.S. Han and C.S. Lee: “Protective effect of boldine on oxidative mitochondrial damage in streptozotocin-induced diabetic rats”, Pharmacol. Res., Vol. 42, (2000), pp. 361–371.

    Article  PubMed  CAS  Google Scholar 

  33. E. Altomare, I. Grattagliano, G. Vendemaile, T. Micelli-Ferrari, A. Signorile and L. Cardia: “Oxidative protein damage in human diabetic eye: evidence of a retinal participation”, Eur. J. Clin. Invest, Vol. 27, (1997), pp. 141–147.

    Article  PubMed  CAS  Google Scholar 

  34. V.M. Bhor, N. Raghuram and S. Sivakami: “Oxidative damage and altered antioxidant enzyme activities in the small intestine of streptozotocin-induced diabetic rats”, Int. J Biochem. Cell Biol., Vol. 36, (2004), pp. 89–97.

    Article  PubMed  CAS  Google Scholar 

  35. H. Esterbauer, R.J. Schaur and H. Zollner: “Chemistry and biochemistry of 4-hydroxynonenal, malonaldehyde and related aldehydes”, Free Radic. Biol. Med., Vol. 11, (1991), pp. 81–128.

    Article  PubMed  CAS  Google Scholar 

  36. A. Amici, R.L. Levine, L. Tsai and E.R. Stadtman: “Conversion of amino acid residues in proteins and amino acid homopolymers to carbonyl derivatives by metal-catalyzed oxidation reactions”, J. Biol. Chem., Vol. 264, (1989), pp. 3341–3346.

    PubMed  CAS  Google Scholar 

  37. F. Shang, X. Gong and A. Taylor: “Activity of ubiquitin-dependent pathway in response to oxidative stress. Ubiquitin-activating enzyme is transiently up-regulated”, J. Biol. Chem., Vol. 272, (1997), pp. 23086–23093.

    Article  PubMed  CAS  Google Scholar 

  38. M. Portero-Otin, R. Pamplona, M.C. Ruiz, E. Cabiscol, J. Prat and M.J. Bellmunt: “Diabetes induces an impairment in the proteolytic activity against oxidized proteins and a heterogeneous effect in nonenzymatic protein modifications in the cytosol of rat liver and kidney”, Diabetes, Vol. 48, (1999), pp. 2215–2220.

    PubMed  CAS  Google Scholar 

  39. K. Okada, C. Wangpoengtrakul, T. Osawa, S. Toyokuni, K. Tanaka and K. Uchida: “4-Hydroxy-2-nonenal-mediated impairment of intracellular proteolysis during oxidative stress. Identification of proteasomes as target molecules”, J. Biol. Chem., Vol. 274, (1999), pp. 23787–23793.

    Article  PubMed  CAS  Google Scholar 

  40. M. Balasubramanyam, R. Sampathkumar and V. Mohan: “Is insulin signaling molecules misguided in diabetes for ubiquitin-proteasome mediated degradation?”, Mol. Cell. Biochem., Vol. 275, (2005), pp. 117–125.

    Article  PubMed  CAS  Google Scholar 

  41. M. Kawaguchi, K. Minami, K. Nagashima and S. Seino: “Essential role of ubiquitin-proteasome system in normal regulation of insulin secretion”, J. Biol. Chem., DOI: 10.1074/jbc.M601228200.

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  1. Institute of Physiology, Bulgarian Academy of Sciences, 1113, Sofia, Bulgaria

    Albena Alexandrova, Lubomir Petrov & Margarita Kirkova

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  1. Albena Alexandrova
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  2. Lubomir Petrov
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  3. Margarita Kirkova
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Alexandrova, A., Petrov, L. & Kirkova, M. Proteasome activity in experimental diabetes. cent.eur.j.biol. 1, 289–298 (2006). https://doi.org/10.2478/s11535-006-0017-3

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  • DOI: https://doi.org/10.2478/s11535-006-0017-3

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