Skip to main content

Advertisement

Log in

Serum prolidase enzyme activity and oxidative stress levels in patients with diabetic neuropathy

  • Original Article
  • Published:
Endocrine Aims and scope Submit manuscript

Abstract

Previous studies have suggested that prolidase and nitric oxide (NO) regulate many processes, such as collagen synthesis and matrix remodeling. Oxidative stress plays an important role in the development of microvascular complications in diabetic patients. Data on serum prolidase activity in patients with diabetes mellitus or diabetic neuropathy (DN) are limited and conflicting. The aim of this study was to measure serum prolidase activity, NO, total antioxidant status (TAS), and malondialdehyde (MDA) levels in patients with DN. Forty-five patients with DN and 40 healthy controls were enrolled. Serum prolidase activity, TAS, MDA, and NO levels were determined. Serum MDA and NO levels were significantly higher in DN patients than controls (p = 0.002, p = 0.001, respectively), while prolidase activity and TAS levels were lower (p = 0.003, p = 0.001, respectively). Prolidase activity was negatively correlated with NO and MDA (r = −0.911, p < 0.001; r = −0.905, p < 0.001, respectively), while positively correlated with TAS (r = 0.981, p < 0.001) in DN patients. The current study is the first showing the decreased serum prolidase enzyme activity. Our results suggest that decreased collagen turnover may occur in DN patients, who have increased oxidative stress and increased NO levels. Decreased prolidase activity seems to be associated with increased NO levels and oxidative stress along with decreased antioxidant levels in DN. Therefore, decreased prolidase activity may play a role in pathogenesis of DN. Prospective clinical studies are necessary to confirm these findings.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

Abbreviations

ROS:

Reactive oxygen species

DM:

Diabetes mellitus

ECM:

Extracellular matrix

NO:

Nitric oxide

NOS:

Nitric oxide synthase

MMPs:

Metalloproteinase

DN:

Diabetic neuropathy

TAS:

Total antioxidant status

MDA:

Malondialdehyde

NO2 /NO3 :

Nitrite/nitrate

HbA1c:

Glycosylated hemoglobin

References

  1. H. Vlassara, Recent progress in advanced glycation end products and diabetic complications. Diabetes 46, 19–25 (1997)

    Article  Google Scholar 

  2. J.W. Baynes, Role of oxidative stress in development of complications in diabetes. Diabetes 40, 405–412 (1991)

    Article  CAS  PubMed  Google Scholar 

  3. B. Sözmen, Y. Delen, F.K. Girgin, E.Y. Sözmen, Catalase and paraoxanase in hypertensive type 2 diabetes mellitus: correlation with glycemic control. Clin. Biochem. 32, 423–427 (1999)

    Article  PubMed  Google Scholar 

  4. A.P. Barbosa, J.L. Medina, E.P. Ramos, H.P. Barros, Prevalence and risk factors of clinical diabetic polyneuropathy in a Portuguese primary health care population. Diabetes Metab. 27, 496–502 (2001)

    CAS  PubMed  Google Scholar 

  5. S. Yamagishi, S. Ueda, T. Matsui, K. Nakamura, S. Okuda, Role of advanced glycation end products (AGEs) and oxidative stress in diabetic retinopathy. Curr. Pharm. Des. 14, 962–968 (2008)

    Article  CAS  PubMed  Google Scholar 

  6. D.R. Sell, V.M. Monnier, End-stage renal disease and diabetes catalyze the formation of a pentose-derived crosslink from aging human collagen. J. Clin. Invest. 85, 380–384 (1990)

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  7. A.C. Newby, K.M. Southgate, M. Davies, Extracellular matrix degrading metalloproteinases in the pathogenesis of arteriosclerosis. Basic Res. Cardiol. 89, 59–70 (1994)

    CAS  PubMed  Google Scholar 

  8. A.P. Boright, C.R. Scriver, G.A. Landcaster, F. Choy, Prolidase deficiency: biochemical classification of alleles. Am. J. Hum. Genet. 44, 731–740 (1989)

    CAS  PubMed Central  PubMed  Google Scholar 

  9. A. Muszynska, J. Palka, E. Gorodkiewicz, The mechanism of daunorubicininduced inhibition of prolidase activity in human skin fibroblasts and its implication to impaired collagen biosynthesis. Exp. Toxicol. Pathol. 52, 149–155 (2000)

    Article  CAS  PubMed  Google Scholar 

  10. J. Palka, W. Miltyk, E. Karna, S. Woczyñski, Modulation of prolidase activity during in vitro aging of human skin fibroblasts the role of extracellular matrix collagen. Tokai J. Exp. Clin. Med. 21, 207–213 (1996)

    CAS  PubMed  Google Scholar 

  11. M. Aslan, Y. Nazligul, M. Horoz, C. Bolukbas, F. Bolukbas, N. Aksoy, H. Celik, O. Erel, Serum prolidase activity and oxidative status in Helicobacter pylori infection. Clin. Biochem. 40, 37–40 (2007)

    Article  CAS  PubMed  Google Scholar 

  12. A. Cakmak, M. Soker, A. Koc, N. Aksoy, Prolidase activity and oxidative status in patients with thalassemia major. J. Clin. Lab. Anal. 24, 6–11 (2000)

    Article  Google Scholar 

  13. R.G. Knowles, S. Moncada, Nitric oxide synthase in mammals. Biochem. J. 198, 249–258 (1994)

    Google Scholar 

  14. T. Tsuruda, L.C. Costello-Boerrigter, J.C. Burnett Jr, Matrix metalloproteinases: pathways of induction by bioactive molecules. Heart Fail. Rev. 9, 53–61 (2004)

    Article  CAS  PubMed  Google Scholar 

  15. S. Araki, M. Haneda, D. Koya, K. Isshiki, S. Kume, T. Sugimoto, H. Kawai, Y. Nishio, A. Kashiwagi, T. Uzu, H. Maegawa, Association between urinary type IV collagen level and deterioration of renal function in type 2 diabetic patients without overt proteinuria. Diabetes Care 33, 1805–1810 (2010)

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  16. R. Hill, Extracellular matrix remodelling in human diabetic neuropathy. J. Anat. 214, 219–225 (2009)

    Article  PubMed Central  PubMed  Google Scholar 

  17. J.L. Bradley, R.H. King, J.R. Muddle, P.K. Thomas, The extracellular matrix of peripheral nerve in diabetic polyneuropathy. Acta Neuropathol. 99, 539–546 (2000)

    Article  CAS  PubMed  Google Scholar 

  18. P.E. Arkkila, T. Ronnemaa, P.J. Koskinen, I.M. Kantola, E. Seppanen, J.S. Viikari, Biochemical markers of type III and I collagen: association with retinopathy and neuropathy in type 1 diabetic subjects. Diabet. Med. 18, 816–821 (2001)

    Article  CAS  PubMed  Google Scholar 

  19. B. Brosset, I. Myara, M. Fabre, A. Lemonnier, Plasma prolidase and prolinase activity in alcoholic liver disease. Clin. Chim. Acta 175, 291–295 (1988)

    Article  CAS  PubMed  Google Scholar 

  20. I. Myara, P. Marcon, A. Lemonnier, B. Chatelier, M. Mangeot, Determination of prolinase activity in plasma. Application to liver disease and its relation with prolidase activity. Clin. Biochem. 18, 220–223 (1985)

    Article  CAS  PubMed  Google Scholar 

  21. R. Demirbag, A. Yildiz, M. Gur, R. Yilmaz, K. Elci, N. Aksoy, Serum prolidase activity in patients with hypertension and its relation with left ventricular hypertrophy. Clin. Biochem. 40, 1020–1025 (2007)

    Article  CAS  PubMed  Google Scholar 

  22. T.R. Evrenkaya, E.M. Atasoyu, M. Kara, S. Unver, M. Gultepe, The role of prolidase activity in the diagnosis of uremic bone disease. Ren. Fail. 28, 271–274 (2006)

    Article  CAS  PubMed  Google Scholar 

  23. F. Gejyo, B.K. Kishore, M. Arakawa, Prolidase and prolinase activities in the erythrocytes of patients with chronic uremia. Nephron 35, 58–61 (1983)

    Article  CAS  PubMed  Google Scholar 

  24. A.B. Erbagci, M. Araz, A. Erbagci, M. Tarakcioglu, E.S. Namiduru, Serum prolidase activity as a marker of osteoporosis in type 2 diabetes mellitus. Clin. Biochem. 35, 263–268 (2002)

    Article  CAS  PubMed  Google Scholar 

  25. O. Altindag, O. Erel, N. Aksoy, S. Selek, H. Celik, M. Karaoglanoglu, Increased oxidative stress and its relation with collagen metabolism in knee osteoarthritis. Rheumatol. Int. 27, 339–344 (2007)

    Article  CAS  PubMed  Google Scholar 

  26. E. Uzar, Y. Tamam, O. Evliyaoglu, A. Tuzcu, C. Beyaz, A. Acar, B. Aydın, N. Tasdemir, Serum prolidase activity and oxidative status in patients with diabetic neuropathy. Neurol. Sci. 33, 875–880 (2012)

    Article  PubMed  Google Scholar 

  27. No authors listed. Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes. Care. 20, 1183-1197 (1997)

    Google Scholar 

  28. No authors listed. American Diabetes Association. Report and recommendations of the San Antonio Conference on diabetic neuropathy. Muscle Nerve 11, 661–667 (1998)

    Google Scholar 

  29. O. Erel, A novel automated direct measurement method for total antioxidant capacity using a new generation more stable ABTS radical cation. Clin. Biochem. 37, 277–285 (2004)

    Article  CAS  PubMed  Google Scholar 

  30. T. Yoshioka, K. Kawada, T. Shimada, M. Mori, Lipid peroxidation in maternal and cord blood and protective mechanisms against activated oxygen toxicity in the blood. Am. J. Obster. Gynecol. 135, 372–376 (1979)

    CAS  Google Scholar 

  31. I. Myara, C. Charpentier, A. Lemonnier, Optimal conditions for prolidase assay by proline colorimetric determination: application to imminodipeptiduria. Clin. Chim. Acta 125, 193–205 (1982)

    Article  CAS  PubMed  Google Scholar 

  32. F.P. Chinard, Photometric estimation of proline and ornithine. J. Biol. Chem. 199, 91–95 (1952)

    CAS  PubMed  Google Scholar 

  33. W.R. Tracey, J. Tse, G. Carter, Lipopolysaccharide-induced changes in plasma nitrite and nitrate concentrations in rats and mice: pharmacological evaluation of nitric oxide synthase inhibitors. J. Pharmacol. Exp. Ther. 272, 1011–1015 (1995)

    CAS  PubMed  Google Scholar 

  34. N.E. Cameron, S.E. Eaton, M.A. Cotter, S. Tesfaye, Vascular factors and metabolic interactions in the pathogenesis of diabetic neuropathy. Diabetologia 44, 1973–1988 (2001)

    Article  CAS  PubMed  Google Scholar 

  35. B.C. Callaghan, H.T. Cheng, C.L. Stables, A.L. Smith, E.L. Feldman, Diabetic neuropathy: clinical manifestations and current treatments. Lancet Neurol. 11, 521–534 (2012)

    Article  PubMed  Google Scholar 

  36. P. Sienkiewicz, M. Palka, J. Palka, Oxidative stress induces IGF-I receptor signaling disturbances in cultured human dermal fibroblasts. A possible mechanism for collagen biosynthesis inhibition. Cell. Mol. Biol. Lett. 9, 643–650 (2004)

    CAS  PubMed  Google Scholar 

  37. M. Savas, E. Yeni, A. Verit, M. Gulum, N. Aksoy, H. Ciftci, A. Altunkol, H. Oncel, Acute effect of phosphodiesterase type 5 inhibitor on serum oxidative status and prolidase activities in men with erectile dysfunction. Clinics (Sao Paulo) 65, 1311–1314 (2010)

    Article  Google Scholar 

  38. Y. Huang, M. Mironova, M.F. Lopes-Virella, Oxidized LDL stimulates matrix metalloproteinase-1 expression in human vascular endothelial cells. Arterioscler. Thromb. Vasc. Biol. 19, 2640–2647 (1999)

    Article  CAS  PubMed  Google Scholar 

  39. M. Navab, J.A. Berliner, A.D. Watson, S.Y. Hama, M.C. Territo, A.J. Lusis, D.M. Shih, B.J. Van Lenten, J.S. Frank, L.L. Demer, P.A. Edwards, A.M. Fogelman, The yin and yang of oxidation in the development of fatty streak: a review based on the 1994 George Lyman Duff Memorial Lecture. Arterioscler. Thromb. Vasc. Biol. 16, 831–842 (1996)

    Article  CAS  PubMed  Google Scholar 

  40. J.M. Mei, G.L. Borchert, S.P. Donald, J.M. Phang, Matrix metalloproteinase (s) mediate (s) NO-induced dissociation of beta-catenin from membrane bound E-cadherin and formation of nuclear beta-catenin/LEF-1 complex. Carcinogenesis 23, 2119–2122 (2002)

    Article  CAS  PubMed  Google Scholar 

  41. A. Surazynski, Y. Liu, W. Miltyk, J.M. Phang, Nitric oxide regulates prolidase activity by serine/threonine phosphorylation. J. Cell. Biochem. 96, 1086–1094 (2005)

    Article  CAS  PubMed  Google Scholar 

  42. M. Aslan, T. Sabuncu, A. Kocyigit, H. Celik, S. Selek, Relationship between total oxidant status and severity of diabetic nephropathy in type 2 diabetic patients. Nutr. Metab. Cardiovasc. Dis. 17, 734–740 (2007)

    Article  CAS  PubMed  Google Scholar 

  43. S.V. Brodsky, A.M. Morrishow, N. Dharia, S.S. Gross, M.S. Goligorsky, Glucose scavenging of nitric oxide. Am. J. Physiol. Renal. Physiol. 280, 480–486 (2001)

    Google Scholar 

  44. S. Srinivasan, M.E. Hatley, D.T. Bolick, L.A. Palmer, D. Edelstein, M. Brownlee, C.C. Hedrick, Hyperglycemia-induced superoxide production decreases eNOS expression via AP-1 activation in aortic endothelial cells. Diabetologia 47, 1727–1734 (2004)

    Article  CAS  PubMed  Google Scholar 

  45. A. Ozkul, M. Ayhan, C. Yenisey, A. Akyol, E. Guney, F.A. Ergin, The role of oxidative stress and endothelial injury in diabetic neuropathy and neuropathic pain. Neuro. Endocrinol. Lett. 31, 261–264 (2010)

    CAS  PubMed  Google Scholar 

  46. V. Ramakrishna, R. Jailkhani, Oxidative stress in non-insulin-dependent diabetes mellitus (NIDDM) patients. Acta Diabetol. 45, 41–46 (2008)

    Article  CAS  PubMed  Google Scholar 

  47. D. Hu, K.A. Jablonski, J.A. Henderson, M.F. Magee, T.K. Welty, D.C. Robbins, B.V. Howard, Glycaemic control in diabetic American Indians. Diabetes Care 22, 1802–1807 (1999)

    Article  CAS  PubMed  Google Scholar 

  48. S.R.J. Maxwell, H. Thomason, D. Sandler, C. LeGuen, M.A. Baxter, G.H. Thorpe, A.F. Jones, A.H. Barnett, Poor glycaemic control is associated with reduced serum free radical scavenging (antioxidant) activity in non-insulin-dependent diabetes mellitus. Ann. Clin. Biochem. 34, 638–644 (1997)

    Article  PubMed  Google Scholar 

  49. I.N. Migdalis, P. Triantafilou, E. Petridou, N. Varvarigos, V. Totolos, A. Rigopoulos, Lipid peroxides in type 2 diabetic patients with neuropathy. Res. Commun. Mol. Pathol. Pharmacol. 117–118, 5–12 (2005)

    PubMed  Google Scholar 

  50. A.M. Vincent, K. Kato, L.L. McLean, M.E. Soules, E.L. Feldman, Sensory neurons and Schwann cells respond to oxidative stress by increasing antioxidant defense mechanisms. Antioxid. Redox Signal. 11, 425–438 (2009)

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  51. C. Figueroa-Romero, M. Sadidi, E.L. Feldman, Mechanisms of disease: the oxidative stress theory of diabetic neuropathy. Rev. Endocr. Metab. Disord. 9, 301–314 (2008)

    Article  CAS  PubMed  Google Scholar 

  52. D.D. Wayner, G.W. Burton, K.U. Ingold, L.R. Barclay, S.J. Locke, The relative contributions of vitamin E, urate, ascorbate and proteins to the total peroxyl radical-trapping antioxidant activity of human blood plasma. Biochim. Biophys. Acta 924, 408–419 (1987)

    Article  CAS  PubMed  Google Scholar 

Download references

Conflict of interest

The authors stated that there are no conflicts of interest regarding the publication of this article.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Mehmet Aslan.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sayın, R., Aslan, M., Kucukoglu, M.E. et al. Serum prolidase enzyme activity and oxidative stress levels in patients with diabetic neuropathy. Endocrine 47, 146–151 (2014). https://doi.org/10.1007/s12020-013-0136-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12020-013-0136-3

Keywords

Navigation