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Prolidase-dependent regulation of collagen biosynthesis

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Abstract

Prolidase [EC.3.4.13.9] is a cytosolic imidodipeptidase, which specifically splits imidodipeptides with C-terminal proline or hydroxyproline. The enzyme plays an important role in the recycling of proline from imidodipeptides (mostly derived from degradation products of collagen) for resynthesis of collagen and other proline-containing proteins. The enzyme activity is up-regulated by β1-integrin receptor stimulation. The increase in the enzyme activity is due to its phosphorylation on serine/threonine residues. Collagen is not only structural component of extracellular matrix. It has been recognized as a ligand for integrin receptors, which play an important role in signaling that regulate ion transport, lipid metabolism, kinase activation and gene expression. Therefore, changes in the quantity, structure and distribution of collagens in tissues may affect cell signaling, metabolism and function. Several line of evidence suggests that prolidase activity may be a step-limiting factor in the regulation of collagen biosynthesis. It has been shown in different physiologic and pathologic conditions. It is of great importance during wound healing, inflammation, aging, tissue fibrosis and possibly skeletal abnormalities seen in Osteogenesis Imperfecta. The mechanism of prolidase-dependent regulation of collagen biosynthesis was found at both transcriptional and post-transcriptional levels. In this study, we provide evidence for prolidase-dependent transcriptional regulation of collagen biosynthesis. The mechanism was found at the level of NF-kB, known inhibitor of type I collagen gene expression. Modulation of integrin-dependent signaling by stimulatory (i.e. thrombin) or inhibitory (i.e. echistatin) β1-integrin ligands or by nitric oxide donors (i.e. DETA/NO) affect prolidase at post-transcriptional level. All those factors may represent novel approach to pharmacotherapy of connective tissue disorders.

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References

  • Adibi SA, Mercer DW (1973) Protein digestion in human intestine as reflected in luminal, mucosal and plasma amino acid concentration after meals. J Clin Invest 52:1586–1591

    Article  PubMed  CAS  Google Scholar 

  • Akiyama SK, Nagata K, Yamada K (1990) Cell surface receptors for extracellular matrix components. Biochim Biophys Acta 1031:91–110

    PubMed  CAS  Google Scholar 

  • Ball SP, Tongue N, Gibaud A, Lependu J, Mollicone R, Gerard R, Oriol R (1991) The human chromosome 19 linkage group FUT1(H), FUT2 (SE), LE, LU, PEPD, C3, APOC2, D19S7 and D19S9. Ann Hum Genet 55:225–233

    Article  PubMed  CAS  Google Scholar 

  • Barua PK, Neiders ME, Topolnycky A, Zambon JJ, Birkedal-Hansen H (1989) Purification of an 80,000-M, glycylprolyl peptidase from Bacteroides gingivalis. Infect Immun 57:2522–2528

    PubMed  CAS  Google Scholar 

  • Bissel M (1981) How does extracellular matrix direct gene expression? J Theor Biol 99:31–68

    Article  Google Scholar 

  • Boright AP, Scriver CR, Lancaster GA, Choy F (1989) Prolidase deficiency: biochemical classification of alleles. Am J Hum Genet 44:731–740

    PubMed  CAS  Google Scholar 

  • Carey DJ (1991) Control of growth and differentiation of vascular cells by extracellular matrix. Ann Rev Physiol 53:161–177

    Article  CAS  Google Scholar 

  • Cechowska-Pasko M, Palka JA, Wojtukiewicz MZ (2006) Enhanced prolidase activity and decreased collage content in breast cancer tissue. Int J Exp Path 87:289–296

    Article  CAS  Google Scholar 

  • Chamson A, Voigtlander V, Myara I, Frey J (1989) Collagen biosynthetic anomalies in prolidase deficiency: effect of glycyl-l-proline on the degradation of newly synthesized collagen. Clin Physiol Biochem 7(3-4):128–136

    PubMed  CAS  Google Scholar 

  • Donjacour AA, Cunha GR (1991) Stromal regulation of epithelial function. Cancer Treat Res 53:335–364

    PubMed  CAS  Google Scholar 

  • Endo F, Hata A, Indo Y, Motohara K, Matsuda I (1987a) Immunochemical analyses of prolidase deficiency and molecular cloning of a cDNA for prolidase of human liver. J Inherit Metab Dis 10:305–307

    Article  PubMed  CAS  Google Scholar 

  • Endo F, Motohara K, Indo Y, Matsuda I (1987b) Immunochemical studies of human prolidase with monoclonal antibodies: absence of the subunit of prolidase in a patient with prolidase deficiency. Pediatr Res 22:627–633

    Article  PubMed  CAS  Google Scholar 

  • Endo F, Tanoue A, Ogata T, Motohara K, Matsuda I (1988) Immunoaffinity purification of human prolidase. Clin Chim Acta 176:143–150

    Article  PubMed  CAS  Google Scholar 

  • Endo F, Tanoue A, Nakai H, Hata A, Indo Y, Titani K, Matsuda I (1989) Primary structure and gene localization of human prolidase. J Biol Chem 264:4476–4481

    PubMed  CAS  Google Scholar 

  • Endo F, Matsuda I (1991) Molecular basis of prolidase (Peptidase D) deficiency. Mol Biol Med 8:117–127

    PubMed  CAS  Google Scholar 

  • Freij BJ, Levy HL, Dudin GL, Mutasim D, Deeb M, Der Kaloustian VA (1984) Clinical and biochemical characteristics of prolidase deficiency in siblings. Am J Med Genet 19:561–566

    Article  PubMed  CAS  Google Scholar 

  • Fremeau RT, Caron MG, Blakely RD (1992) Molecular cloning and expression of a high affinity l-proline transporter expressed in putative glutamatergic pathways of rat brain. Neuron 8:915–926

    Article  PubMed  CAS  Google Scholar 

  • Galicka A, Wolczynski S, Anchim T, Surazynski A, Lesniewicz R, Palka J (2001) Defects of type I procollagen metabolism correlated with decrease of prolidase activity in a case of lethal osteogenesis imperfecta. Eur J Biochem 268:2172–2178

    Article  PubMed  CAS  Google Scholar 

  • Ghosh M, Grunden AM, Dunn DM, Weiss R, Adams WW (1998) Characterization of native and recombinants forms of an unusual cobalt-dependent proline dipeptidase (Prolidase) from the hypertermophilic archaeon Pyrococcus furiosus. J Bacteriology 180:4781–4789

    CAS  Google Scholar 

  • Goodman SI, Solomons CC, Muschenheim F, Macintyre CA, Miles B, O′Brien D (1968) A syndrome resembling lathyrism associated with iminodipeptiduria. Am J Med 45:152–159

    Article  PubMed  CAS  Google Scholar 

  • Hui KS, Lajtha A (1978) Peptidase activity in brain: comparison with other organs. J Neurochem 30:321–328

    Article  PubMed  CAS  Google Scholar 

  • Isemura M, Hanyu T, Gejyo F, Nakazawa R, Igarashi R, Matsuo S, Ikeda K, Sato Y (1979) Prolidase deficiency with imidodipeptiduria. A familial case with and without clinical symptoms. Clin Chim Acta 93:401–409

    Article  PubMed  CAS  Google Scholar 

  • Ivaska J, Reunanen H, Westermarck J, Koivisto L, Kahari VM, Heino J (1999) Integrin α2β1 mediates isoform-specific activation of p38 and up-regulation of collagen gene transcription by a mechanism involving the alpha2 cytoplasmic tail. J Cell Biol 147:401–416

    Article  PubMed  CAS  Google Scholar 

  • Jackson SH, Dennis AN, Greenberg M (1975) Iminopeptiduria. A genetic defect in recycling collagen: a method for determining prolidase in red blood cells. Can Med Assoc J 113:759–763

    PubMed  CAS  Google Scholar 

  • Juliano RL, Haskill S (1993) Signal transduction from the extracellular matrix. J Cell Biol 120:577–585

    Article  PubMed  CAS  Google Scholar 

  • Karna E, Surazynski A, Palka J (2000) Collagen metabolism disturbances are accompanied by an increase in prolidase activity in lung carcinoma planoepitheliale. Int J Exp Path 81:341–347

    Article  CAS  Google Scholar 

  • Karna E, Surazynski A, Orlowski K, Laszkiewicz J, Puchalski Z, Nawrat P, Palka J (2002) Serum and tissue level of insulin-like growth factor-I (IGF-I) and IGF-I binding proteins as an index of pancreatitis and pancreatic cancer. Int J Exp Pathol 83:239–245

    Article  PubMed  CAS  Google Scholar 

  • Karna E, Miltyk W, Palka J, Jarzabek K, Wolczynski S (2006) Hyaluronic acid counteracts interleukin-1-induced inhibition of collage biosynthesis In cultured human chondrocytes. Pharmacol Res 54:275–281

    Article  PubMed  CAS  Google Scholar 

  • King GF, Kuchel PW (1984) A proton NMR study of imidodipeptide transport and hydrolysis in the human erythrocyte. Biochem J 220:553–560

    PubMed  CAS  Google Scholar 

  • King GF, Middlehurst CR, Kichel PW (1986) Direct NMR evidence that prolidase is specific for the trans isomer of imidodipeptide substrate. Biochemistry 25:1054–1059

    Article  PubMed  CAS  Google Scholar 

  • King GF, Crossley MJ, Kuchel PW (1989) Inhibition and active-site modelling of prolidase. Eur J Biochem 180:377–384

    Article  PubMed  CAS  Google Scholar 

  • Kouba DJ, Chung KY, Nishiyama T, Vindevoghel L, Kon A, Klement JF, Uitto J, Mauviel A (1999) Nuclear factor-kappa B mediates TNF-alpha inhibitory effect on alpha 2(I) collagen (COL1A2) gene transcription in human dermal fibroblasts. J Immunol 162:4226–4234

    PubMed  CAS  Google Scholar 

  • Labat-Robert J, Robert L (2000) Interaction between cells and extracellular matrix: signaling by integrins and the elastin-laminin receptor. Prog Mol Subcell Biol 25:57–70

    PubMed  CAS  Google Scholar 

  • Ledoux P, Scriver C, Hechtman P (1991) Molecular heterogeneity and variable clinical expression at the PEPD locus. Am J Hum Genet 49:411–415

    Google Scholar 

  • Ledoux P, Scriver CR, Hechtman P (1996) Expression and molecular analysis of mutations in deficiency. Am J Hum Genet 59:1035–1039

    PubMed  CAS  Google Scholar 

  • Lemieux B, Auray-Blais C, Giguere R, Shapcott D (1984) Prolidase deficiency: detection of cases by a newborn urinary screening program. J Inherit Metab Dis 7:145–148

    Article  PubMed  Google Scholar 

  • Lin LN, Brandts JF (1979) Role of cis–trans isomerism of the peptide bond in protease specificity. Kinetic studies on small proline-containing peptides and on polyproline. Biochemistry 18:43–47

    Article  PubMed  CAS  Google Scholar 

  • Lupi A, Rossi E, Vaghi P, Gallanti A, Cetta G, Forlino A (2005) N-benzyloxycarbonyl-l-proline: an in vitro and in vivo inhibitor of prolidase. Biochim Biophys Acta 1744:157–163

    Article  PubMed  CAS  Google Scholar 

  • Lupi A, Della Torre S, Campari E, Tenni R, Cetta G, Rosii A, Forlino A (2006a) Human recombinant prolidase from eucaryotic and procaryotic sources. Expression, purification, characterization and long-term stability studies. FEBS J 273:5466–5478

    Article  PubMed  CAS  Google Scholar 

  • Lupi A, Rossi E, Campari E, Pecora F, Lund AM, Elcioglu NH, Gultepe M, Di Rocco M, Cetta G, Forlino A (2006b) Molecular characterization of six patients with prolidase deficiency: identification of the first small duplication in the prolidase gene and of a mutation generating symptomatic and asymptomatic outcomes within the same family. J Med Genet 43:e58

    Article  PubMed  CAS  Google Scholar 

  • Miltyk W, Karna E, Palka J (1996) Inhibition of prolidase activity by non-steroid anti-inflammatory drugs in cultured human skin fibroblasts. Pol J Pharmacol 48:609–613

    PubMed  CAS  Google Scholar 

  • Miltyk W, Karna E, Wolczynski S, Palka J (1998) Insulin-like growth factor I-dependent regulation of prolidase activity in cultured human skin fibroblasts. Mol Cell Biochem 189:177–183

    Article  PubMed  CAS  Google Scholar 

  • Miltyk W, Palka J (2000) Potential role of pyrroline 5-carboxylate in regulation of collagen biosynthesis in cultured human skin fibroblasts. Comp Biochem Physiol A Mol Integr Physiol 125:265–271

    Article  PubMed  CAS  Google Scholar 

  • Miltyk W, Surazynski A, Kasprzak KS, Fivash MJ Jr, Buzard GS, Phang JM (2005) Inhibition of prolidase activity by nickel causes decreased growth of proline auxotrophic CHO cells. J Cell Biochem 94:1210–1217

    Article  PubMed  CAS  Google Scholar 

  • Miltyk W, Karna E, Palka JA (2007) Prolidase-independent mechanism of camptothecin-induced inhibition of collagen biosynthesis in cultured human skin fibroblasts. J Biochem 141:287–292

    Article  PubMed  CAS  Google Scholar 

  • Mock WL, Green PC, Boyer KD (1990) Specificity and pH dependence acylproline cleavage by prolidase. J Biol Chem 265:19600–19605

    PubMed  CAS  Google Scholar 

  • Mock WL, Green PC (1991) Mechanism and inhibition of prolidase. J Biol Chem 265:19606–19610

    Google Scholar 

  • Mock WL, Zhuang H (1991) Chemical modification locates guanidinyl and carboxylate groups within the active site of prolidase. Biochem Biophys Res Commun 180:401–406

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Myara I, Charpentier C, Lemonnier A (1984) Minireview: prolidase and prolidase deficiency. Life Sci 34:1985–1998

    Article  PubMed  CAS  Google Scholar 

  • Naughten ER, Proctor SP, Levy HL, Coulombe JT, Amplola MG (1984) Congenital expression of prolidase defect in prolidase deficiency. Ped Res 18:259–264

    Article  CAS  Google Scholar 

  • Pałka JA, Miltyk W, Karna E, Wołczyński S (1996) Modulation of prolidase activity during in vitro aging of human skin fibroblasts. The role of extracellular matrix collagen. Tokai J Exp Clin Med 21:207–13

    PubMed  Google Scholar 

  • Palka JA, Phang JM (1997) Prolidase activity in fibroblasts is regulated by interaction of extracellular matrix with cell surface integrin receptor. J Cell Biochem 67:166–175

    Article  PubMed  CAS  Google Scholar 

  • Peterkofsky B, Chojkier M, Bateman J (1982) Determination of collagen synthesis in tissue and cell culture system. In: Furthmayr (ed) Immunochemistry of the extracellular matrix. CRC Press, Boca Raton, pp 19–47

  • Phang JM, Scriver CR (1989) In: Scriver CR, Beaudet AL, Sly WS, Valle D (eds) The metabolic basis of inherited disease. Disorders of proline and hydroxyproline metabolism. McGraw Hill, New York, pp 577–597

  • Pierard GE, Cornil F, Lapiere CHM (1984) Pathogenesis of ulcerations in deficiency of prolidase. Am J Dermatopathol 6:491–498

    Article  PubMed  CAS  Google Scholar 

  • Powell GH, Maniscalco RM (1976) Bound hydroxyproline excretion following gelatin loading in prolidase deficiency. Metabolism 25:503–508

    Article  PubMed  CAS  Google Scholar 

  • Reid KBM, Porter RR (1976) A collagen-like amino acid sequence in a polypeptide chain of human C1q (a subcomponent of the first component of complement). Biochem J 155:19–23

    PubMed  CAS  Google Scholar 

  • Richter AM, Lancaster GA, Choy FYM, Hechtman P (1989) Purification and characterization of activate human erythrocyte prolidase. Biochem Cell Biol 67:34–39

    Article  PubMed  CAS  Google Scholar 

  • Rippe RA, Schrum LW, Stefanovic B, Solís-Herruzo JA, Brenner DA (1999) NF-kappaB inhibits expression of the alpha1(I) collagen gene. DNA Cell Biol 18:751–761

    Article  PubMed  CAS  Google Scholar 

  • Scriver CR (1964) Glycyl-proline in urine of humans with bone disease. Can J Physiol Pharmacol 42:357–364

    PubMed  CAS  Google Scholar 

  • Seger R, Krebs EG (1995) The MAPK signaling cascade. FEBS J 9:726–735

    CAS  Google Scholar 

  • Sjostrom H, Noren O, Josefsson L (1973) Purification and specificity of pig intestinal prolidase. Biochim Biophys Acta 327:457–470

    PubMed  CAS  Google Scholar 

  • Sjostrom H (1974) Enzymatic properties of pig intestinal proline dipeptidase. Acta Chem Scand B 28:802–808

    Article  PubMed  CAS  Google Scholar 

  • Sjostrom H, Noren O (1991) Structural properties of pig intestinal proline dipeptidase. Biochim Biophys Acta 359:177–185

    Google Scholar 

  • Surazynski A, Sienkiewicz P, Wolczynski S, Palka J (2005a) Differential effect of echistatin and thrombin on collagen production and prolidase activity in human dermal fibroblasts and their possible implication in beta1-integrin-mediated signaling. Pharmacol Res 51:217–221

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Surazynski A, Donald SP, Cooper SK, Whiteside MA, Salnikow K, Liu Y, Phang JM (2008) Extracellular matrix and HIF-1 signaling: the role of prolidase. Int J of Cancer (in press)

  • Tanoue A, Endo F, Matsuda I (1990) Structural organization of the gene for human prolidase (peptidase D) and demonstration of a partial gene deletion in a patient with prolidase deficiency. J Biol Chem 265:11306–11311

    PubMed  CAS  Google Scholar 

  • Tanoue A, Endo F, Akaboshi I, Oono T, Arata J, Matsuda I (1991) Molecular defect in siblings with prolidase deficiency and absence or presence of clinical symptoms. J Clin Invest 87:1171–1176

    Article  PubMed  CAS  Google Scholar 

  • Umemura S (1978) Studies on a patient with iminodipeptiduria. II. Lack of prolidase activity in blood cells. Physiol Chem Phys 10:279–285

    PubMed  CAS  Google Scholar 

  • Uramatsu M, Liu G, Uramatsu S, Zhang M, Wang W, Nakayama K, Manabe M, Kodama H (2007) Different effects of sulfur amino acids on prolidase and prolinase activity in normal and prolidase-deficient human erythrocytes. Clin Chim Acta 375:129–135

    Article  PubMed  CAS  Google Scholar 

  • Wang SH, Zhi QW, Sun MJ (2006) Dual activities of human prolidase. Toxicol In Vitro 20:71–77

    Article  PubMed  CAS  Google Scholar 

  • Yaron A, Naider F (1993) Proline-dependent structural and biological properties of peptides and proteins. Crit Rev Biochem Mol Biol 28:31–81

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Medicinal Chemistry, Medical University of Bialystok, ul. Kilińskiego 1, 15-089, Bialystok, Poland

    A. Surazynski, W. Miltyk & J. Palka

  2. Laboratory of Comparative Carcinogenesis, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, MD, USA

    J. M. Phang

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  1. A. Surazynski
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  2. W. Miltyk
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  3. J. Palka
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  4. J. M. Phang
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Correspondence to J. Palka.

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Surazynski, A., Miltyk, W., Palka, J. et al. Prolidase-dependent regulation of collagen biosynthesis. Amino Acids 35, 731–738 (2008). https://doi.org/10.1007/s00726-008-0051-8

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