Skip to main content
PMC home page
Journal of Clinical Laboratory Analysis logoLink to Journal of Clinical Laboratory Analysis
. 2010 Jan 19;24(1):6–11. doi: 10.1002/jcla.20361

Prolidase activity and oxidative status in patients with thalassemia major

Alpay Cakmak 1,✉, Murat Soker 2, Ahmet Koc 3, Nurten Aksoy 4
PMCID: PMC6647656  PMID: 20087956

Abstract

Aim: Prolidase is a specific imidodipeptidase involved in collagen degradation. The increase in the enzyme activity is believed to be correlated with the increased intensity of collagen degradation. The study aimed to evaluate the relationship between prolidase activity and oxidative status in patients with thalassemia major. Methods: Comparison was made between 87 patients diagnosed with thalassemia major and 33 healthy children of similar age and gender. Mean age of the subjects was 7.5±4.3 years in the group of patients with thalassemia major and 8.9±3.1 years in the control group. Serum prolidase activity was measured spectrophotometrically. Oxidative status was determined using total oxidant status (TOS), total antioxidant capacity (TAC), and oxidative stress index (OSI) measurement. Results: Prolidase activity was significantly increased in patients with thalassemia major (53.7±8.7 U/l) compared to the control group (49.2±7.2 U/l, P<0.001). TOS was significantly increased in the patient group (5.31±3.14 mmol H2O2 equiv./l) compared to the control group (3.49±2.98 μmol H2O2 equiv./l) and the OSI was also significantly increased in the patient group (3.86±3.28 arbitrary unit) compared to the control group (2.53±2.70 arbitrary unit) (P<0.0001 and P<0.001, respectively), while there were no significant differences between the patient (1.61±0.30 μmol Trolox equiv./l) and control (1.64±0.33 μmol Trolox equiv./l) groups with respect to TAC. Conclusion: Significant increases in prolidase activity in patients with thalassemia major may constitute a key parameter in demonstrating a disorder of the collagen metabolism. J. Clin. Lab. Anal. 24:6–11, 2010. © 2010 Wiley‐Liss, Inc.

Keywords: thalassemia major, prolidase activity, collagen, oxidative status

REFERENCES

  • 1. Myara I, Charpentier C, Lemonnier A. Prolidase and prolidase deficiency. Life Sci 1984;34:1985–1998. [DOI] [PubMed] [Google Scholar]
  • 2. Gürdol F, Genç S, Yalçin Ö, Gültepe M. The presence of prolidase activity in amniotic fluid and its evaluation as a maturity test. Biol Neonate 1995;67:34–38. [DOI] [PubMed] [Google Scholar]
  • 3. Yaron A, Naider F. Proline‐dependent structural and biological properties of peptides and proteins. Crit Rev Biochem Mol Biol 1993;28:31–81. [DOI] [PubMed] [Google Scholar]
  • 4. Emmerson KS, Phang JM. Hydrolysis of proline dipeptides completely fulfills the proline requirement in a proline‐auxotropic Chinese hamster ovary cell line. J Nutr 1993;123:909–914. [DOI] [PubMed] [Google Scholar]
  • 5. Jackson SH, Dennis AW, Greenberg M. Iminodipeptiduria: A genetic defect in recycling collagen; A method for determining prolidase in erythrocytes. Can Med Assoc J 1975;113:762–763. [PMC free article] [PubMed] [Google Scholar]
  • 6. Myara I, Myara A, Mangeat M, Fabre M, Carpentier C, Lemonier A. Plasma prolidase activity: A possible index of collagen catabolism in chronic liver disease. Clin Chem 1984;30:211–215. [PubMed] [Google Scholar]
  • 7. Hui KS, Lajtha A. Prolidase activity in brain: Comparison with other organs. J Neurochem 1978;30:321–327. [DOI] [PubMed] [Google Scholar]
  • 8. Keser I, Sanlioglu AD, Manguoglu E, et al. Molecular analysis of beta‐thalassemia and sickle cell anemia in Antalya. Acta Haematol 2004;111:205–210. [DOI] [PubMed] [Google Scholar]
  • 9. Vaskaridou E, Kyrtsonis MC, Terpos E, et al. Bone resorption is increased in young adults with thalassaemia major. Br J Haematol 2002;112:36–41. [DOI] [PubMed] [Google Scholar]
  • 10. Wonke B. Annotation: Bone disease in thalassemia major. Br J Haematol 1998;103:897–901. [DOI] [PubMed] [Google Scholar]
  • 11. Grant SF, Reid DM, Blake G, et al. Reduced bone density osteoporosis associated with a polymorphic sp1 binding site in the collagen type a1 gene. Nat Genet 1996;14:203–205. [DOI] [PubMed] [Google Scholar]
  • 12. Perrotta S, Cappellini MD, Bertoldo F, et al. Osteoporosis in beta‐thalassemia major patients: Analysis of the genetic background. Br J Haematol 2000;111:461–466. [DOI] [PubMed] [Google Scholar]
  • 13. Ralston SH. Genetic control of susceptibility to osteoporosis. J Clin Endocrinol Metab 2002;86:2460–2466. [DOI] [PubMed] [Google Scholar]
  • 14. Wonke B, Jensen C, Hanslip JJ, et al. Genetic and acquired predisposing factors and treatment of osteoporosis in thalassaemia major. J Pediatr Endocrinol Metab 1998;3:795–801. [PubMed] [Google Scholar]
  • 15. Rund D, Rachmilewitz E. Beta‐thalassemia. N Engl J Med 2005;353:1135–1146. [DOI] [PubMed] [Google Scholar]
  • 16. Voskaridou E, Terpos E. New insights into the pathophysiology and management of osteoporosis in patients with beta thalassaemia. Br J Haematol 2004;127:127–139. [DOI] [PubMed] [Google Scholar]
  • 17. Jensen CE, Tuck SM, Agnew JE, et al. High incidence of osteoporosis in thalassaemia major. J Pediatr Endocrinol Metab 1998;11:975–977. [PubMed] [Google Scholar]
  • 18. Shamshirsaz AA, Bekheirnia MR, Kamgar M, et al. Metabolic and endocrinologic complications in beta‐thalassemia major: A multicenter study in Tehran. BMC Endocr Disord 2003;3:4. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 19. Myara I, Charpentier C, Lemonnier A. Optimal conditions for prolidase assay by proline colorimetric determination: Application to iminodipeptiduria. Clin Chim Acta 1982;125:193–205. [DOI] [PubMed] [Google Scholar]
  • 20. Chinard FP. Photometric estimation of proline and ornithine. J Biol Chem 1952;199:91–95. [PubMed] [Google Scholar]
  • 21. Erel O. A novel automated method to measure total antioxidant response against potent free radical reactions. Clin Biochem 2004;37:112–119. [DOI] [PubMed] [Google Scholar]
  • 22. Erel O. A new automated colorimetric method for measuring total oxidant status. Clin Biochem 2005;38:1103–1111. [DOI] [PubMed] [Google Scholar]
  • 23. Kosecik M, Erel O, Sevinc E, et al. Increased oxidative stress in children exposed to passive smoking. Int J Cardiol 2005;100:61–64. [DOI] [PubMed] [Google Scholar]
  • 24. Kurien BT, Patel NC, Porter AC, et al. Prolidase deficiency and the biochemical assays used in its diagnosis. Anal Biochem 2005;349:165–175. [DOI] [PubMed] [Google Scholar]
  • 25. Lasco A, Morabito N, Gaudio A, Buemi M, Wasniewska M, Frisina N. Effects of hormonal replacement therapy on bone metabolism in young adults with beta‐thalassemia major. Osteoporos Int 2001;12:570–575. [DOI] [PubMed] [Google Scholar]
  • 26. Liu YZ, Liu YJ, Recker RR, Deng HW. Molecular studies of identification of genes for osteoporosis: The 2002 update. J Endocrinol 2003;177:147–196. [DOI] [PubMed] [Google Scholar]
  • 27. Lawrence GR. Pathogenesis of osteoporosis: Concepts, conflicts and prospects. J Clin Invest 2005;115:3318–3325. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 28. Dresner PR, Rachmilewitz E, Blumenfeld A, Idelson M, Goldfarb AW. Bone mineral metabolism in adults with beta‐thalassaemia major and intermedia. Br J Haematol 2000;111:902–907. [PubMed] [Google Scholar]
  • 29. Kyriakou A, Savva SC, Savvides I, et al. Gender differences in the prevalence and severity of bone disease in thalassaemia. Pediatr Endocrinol Rev 2008;6:116–122. [PubMed] [Google Scholar]
  • 30. Toker A, Aksoy H, Borekci B, Oskan A. Correlations of serum IL‐6 levels and prolidase activity between bone turnover markers and bone mineral density in postmenopausal women with and without osteoporosis. Turk J Med Sci 2007;37:129–134 [Google Scholar]
  • 31. Namiduru ES, Binnur Erbagci A, Celik A, Yilmaz M, Tarakçioglu M. Serum prolidase activity in postmenopausal osteoporosis. Minerva Med 2007;98:647–651 [PubMed] [Google Scholar]
  • 32. Evrenkaya TR, Atasoyu EM, Kara M, Unver S, Gultepe M. The role of prolidase activity in the diagnosis of uremic bone disease. Ren Fail 2006;28:271–274. [DOI] [PubMed] [Google Scholar]
  • 33. Erbagci AB, Araz M, Erbagci A, Tarakçioglu M, Namiduru ES. Serum prolidase activity as a marker of osteoporosis in type 2 diabetes mellitus. Clin Biochem 2002;35:263–268. [DOI] [PubMed] [Google Scholar]
  • 34. Surazynski A, Miltyk W, Palka J, Phang JM. Prolidase‐dependent regulation of collagen biosynthesis. Amino Acids 2008;35:731–738. [DOI] [PubMed] [Google Scholar]
  • 35. Lupi A, Tenni R, Rossi A, Cetta G, Forlino A. Human prolidase and prolidase deficiency: An overview on the characterization of the enzyme involved in proline recycling and on the effects of its mutations. Amino Acids 2008;35:739–752. [DOI] [PubMed] [Google Scholar]
  • 36. Livrea MA, Tesoriere L, Maggio A, et al. Oxidative modification of low density lipoprotein and atherogenetic risk in beta‐thalassemia. Blood 1998;92:3936–3942. [PubMed] [Google Scholar]
  • 37. Barrano B, Bertrand G, Isaja T, et al. Plasma homocysteine is not involved in the thrombotic risk of b‐thalassemia major patients. Acta Haematologica 2000;104:148–150. [DOI] [PubMed] [Google Scholar]
  • 38. Tesoriere L, Arpa D, Moggio A, et al. Oxidation resistance of LDL is correlated with vitamin E status in betathalassemia intermedia. Atheroseclerosis 1998;137:429–435 [DOI] [PubMed] [Google Scholar]
  • 39. Knutson MD, Walter PB, Ames BN, et al. Both iron deficiency and daily iron supplements increase lipid peroxidation in rats. J Nutr 2000;130:621–628. [DOI] [PubMed] [Google Scholar]
  • 40. Walter PB, Knutson MD, Paler‐ Martinez A, et al. Iron deficiency and iron excess damage mitochondria and mitochondrial DNA in rats. Proc Natl Acad Sci USA 2002;99:2264–2269. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 41. Tesoriere L, D'Arpa D, Butera D, et al. Oral supplements of vitamin E improve measures of oxidative stress in plasma and reduce oxidative damage to LDL and erythrocytes in beta‐thalassemia intermedia patients. Free Radic Res 2001;34:529–540. [DOI] [PubMed] [Google Scholar]
  • 42. Kassab‐Chekir A, Laradi S, Ferchichi S, et al. Oxidant, antioxidant status and metabolic data in patients with betathalassemia. Clin Chim Acta 2003;338:79–86. [DOI] [PubMed] [Google Scholar]
  • 43. Dhawan V, Kumar KHR, Marwaha RK, et al. Antioxidant status in children with homozygous beta thalassemia. Indian Pediatr 2005;42:1141–1145. [PubMed] [Google Scholar]
  • 44. Vives Corrons JL, Miguel‐Garcia A, Pujades MA, et al. Increased susceptibility of microcytic red blood cells to in vitro oxidative stress. Eur J Haematol 1995;55:327–331. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Laboratory Analysis are provided here courtesy of Wiley

RESOURCES