SpringerLink
Log in

Molecular cloning, expression, and characterization of cyclophilin A from Clonorchis sinensis

  • Original Paper
  • Published:
Parasitology Research Aims and scope Submit manuscript

Abstract

This study described the recognization, cloning, and recombinant expression of cyclophilin A-like gene from Clonorchis sinensis adult complementary DNA library (CsCyPA) and its expression and secretion in adult. Western blotting demonstrated the recombinant CsCyPA could be recognized by sera of clonorchiasis patients and a sole protein of the same size in the excretory-secretory antigens of in vitro cultured adult could be recognized by antiserum raised against the recombinant CsCyPA. Immunohistochemistry demonstrated that the CsCyPA was secreted in scattered vesicles from subtegumental parenchyma cells to the surface of tegument and mainly released from the tegument. ELISA showed the serum levels of IgG against CsCyPA in clonorchiasis patients negatively correlated with worm loads. This study suggested that C. sinensis adult in biliary ducts could release CsCyPA without signal peptide through nonclassical secretory pathway into the liver and might play a role in inflammation and biliary epithelium proliferation and adenomatoid hyperplasia.

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

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price includes VAT (Germany)

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  • Al-Ghoul M, Brück TB, Lauer-Fields JL, Asirvatham VS, Zapata C, Kerr RG, Fields GB (2008) Comparative proteomic analysis of matched primary and metastatic melanoma cell lines. J Proteome Res 7:4107–4118

    Article  PubMed  CAS  Google Scholar 

  • Allain F, Vanpouille C, Carpentier M, Slomianny MC, Durieux S, Spik G (2002) Interaction with glycosaminoglycans is required for cyclophilin B to trigger integrin-mediated adhesion of peripheral blood T lymphocytes to extracellular matrix. Proc Natl Acad Sci USA 99:2714–2719

    Google Scholar 

  • Espino AM, Diaz A, Perez A, Finlay CM (1998) Dynamics of antigenemia and coproantigens during a human Fasciola hepatica outbreak. J Clin Microbiol 36:2723–2726

    PubMed  CAS  Google Scholar 

  • Billich A, Winkler G, Aschauer H, Rot A, Peichl P (1997) Presence of cyclophilin A in synovial fluids of patients with rheumatoid arthritis. J Exp Med 185:975–980

    Article  PubMed  CAS  Google Scholar 

  • Candé C, Vahsen N, Kouranti I, Schmitt E, Daugas E, Spahr C, Luban J, Kroemer RT, Giordanetto F, Garrido C, Penninger JM, Kroemer G (2004) AIF and cyclophilin A cooperate in apoptosis-associated chromatinolysis. Oncogene 3:1514–1521

    Article  Google Scholar 

  • Chen X, Hu X, Wu Z, Yu X, Ma C, Zhou Z (2007) Immunological cross-reactivity analysis on recombinant histamine-releasing factors from Schistosoma japonicum, Clonorchis sinensis, and Wistar rat. Parasitol Res 100:749–754

    Article  PubMed  Google Scholar 

  • Choi KJ, Piao YJ, Lim MJ, Kim JH, Ha J, Choe W, Kim SS (2007) Overexpressed Cyclophilin A in cancer cells renders resistance to hypoxia- and cisplatin-induced cell death. Cancer Res 67:3654–3662

    Article  PubMed  CAS  Google Scholar 

  • Edgar CE, Lindquist LD, McKean DL, Strasser A, Bram RJ (2010) CAML regulates Bim-dependent thymocyte death. Cell Death Differ 17:1566–1576

    Article  PubMed  CAS  Google Scholar 

  • Fischer G, Wittmann-Liebold B, Lang K, Kiefhaber T, Schmid FX (1989) Cyclophilin and peptidyl-prolyl cis-trans isomerase are probably identical proteins. Nature 337:476–478

    Article  PubMed  CAS  Google Scholar 

  • Gaither LA, Borawski J, Anderson LJ, Balabanis KA, Devay P, Joberty G, Rau C, Schirle M, Bouwmeester T, Mickanin C, Zhao S, Vickers C, Lee L, Deng G, Baryza J, Fujimoto RA, Lin K, Compton T, Wiedmann B (2010) Multiple cyclophilins involved in different cellular pathways mediate HCV replication. Virology 397:43–55

    Article  PubMed  CAS  Google Scholar 

  • Galat A (1999) Variations of sequences and amino acid compositions of proteins that sustain their biological functions: an analysis of the cyclophilin family of proteins. Arch Biochem Biophys 371:149–162

    Article  PubMed  CAS  Google Scholar 

  • Handschumacher RE, Harding MW, Rice J, Drugge RJ, Speicher DW (1984) Cyclophilin: a specific cytosolic binding protein for cyclosporin A. Science 226:544–547

    Article  PubMed  CAS  Google Scholar 

  • Hu F, Yu X, Ma C, Zhou H, Zhou Z, Li Y, Lu F, Xu J, Wu Z, Hu X (2007) Clonorchis sinensis: expression, characterization, immunolocalization and serological reactivity of one excretory/secretory antigen-LPAP homologue. Exp Parasitol 117:157–164

    Article  PubMed  CAS  Google Scholar 

  • Hu F, Hu X, Ma C, Zhao J, Xu J, Yu X (2009) Molecular characterization of a novel Clonorchis sinensis secretory phospholipase A(2) and investigation of its potential contribution to hepatic fibrosis. Mol Biochem Parasitol 167:127–134

    Article  PubMed  CAS  Google Scholar 

  • Ivery MT (2000) Immunophilins: switched on protein binding domains? Med Res Rev 20:452–484

    Article  PubMed  CAS  Google Scholar 

  • ** ZG, Melaragno MG, Liao DF, Yan C, Haendeler J, Suh YA, Lambeth JD, Berk BC (2000) Cyclophilin A is a secreted growth factor induced by oxidative stress. Circ Res 87:789–796

    PubMed  CAS  Google Scholar 

  • Kratz A, Harding MW, Craft J, Mackworth-Young CG, Handschumacher RE (1992) Autoantibodies against cyclophilin in systemic lupus erythematosus and Lyme disease. Clin Exp Immunol 90:422–427

    Article  PubMed  CAS  Google Scholar 

  • Li Y, Hu X, Xu J, Hu F, Ma C, Yu X (2009a) Molecular cloning and analysis of stage and tissue-specific expression of Cathepsin L-like protease from Clonorchis sinensis. J Parasitol Res 105:447–452

    Article  Google Scholar 

  • Li Y, Kar AK, Sodroski J (2009b) Target cell type-dependent modulation of human immunodeficiency virus type 1 capsid disassembly by cyclophilin A. J Virol 83:10951–10962

    Article  PubMed  CAS  Google Scholar 

  • Lun ZR, Gasser RB, Lai DH, Li AX, Zhu XQ, Yu XB, Fang YY (2005) Clonorchiasis: a key foodborne zoonosis in China. Lancet Infect Dis 5:31–41

    Article  PubMed  Google Scholar 

  • Ma C, Hu X, Hu F, Li Y, Chen X, Zhou Z, Lu F, Xu J, Wu Z, Yu X (2007) Molecular characterization and serodiagnosis analysis of a novel lysophospholipase from Clonorchis sinensis. Parasitol Res 101:419–425

    Article  PubMed  Google Scholar 

  • Marks AR (1996) Cellular functions of immunophilins. Physiol Rev 76:631–649

    PubMed  CAS  Google Scholar 

  • Montague JW, Gaido ML, Frye C, Cidlowski JA (1994) A calcium-dependent nuclease from apoptotic rat thymocytes is homologous with cyclophilin. Recombinant cyclophilins A, B, and C have nuclease activity. J Biol Chem 269:18877–18880

    PubMed  CAS  Google Scholar 

  • Peng H, Vijayakumar S, Schiene-Fischer C, Li H, Purkerson JM, Malesevic M, Liebscher J, Al-Awqati Q, Schwartz GJ (2009) Secreted cyclophilin A, a peptidylprolyl cis-trans isomerase, mediates matrix assembly of hensin, a protein implicated in epithelial differentiation. J Biol Chem 284:6465–6475

    Article  PubMed  CAS  Google Scholar 

  • Qi YJ, He QY, Ma YF, Du YW, Liu GC, Li YJ, Tsao GS, Ngai SM, Chiu JF (2008) Proteomic identification of malignant transformation-related proteins in esophageal squamous cell carcinoma. J Cell Biochem 104:1625–1635

    Article  PubMed  CAS  Google Scholar 

  • Satoh K, Shimokawa H, Berk BC (2010) Cyclophilin A: promising new target in cardiovascular therapy. Circ J 74(11):2249–2256

    Article  PubMed  CAS  Google Scholar 

  • Schreiber SL (1992) Immunophilin-sensitive protein phosphatase action in cell signaling pathways. Cell 70:365–368

    Article  PubMed  CAS  Google Scholar 

  • Seko Y, Fujimura T, Taka H, Mineki R, Murayama K, Nagai R (2004) Hypoxia followed by reoxygenation induces secretion of cyclophilin A from cultured rat cardiac myocytes. Biochem Biophys Res Commun 317:162–168

    Article  PubMed  CAS  Google Scholar 

  • Sherry B, Yartlett N, Strupp A, Cerami A (1992) Identification of cyclophilin as a proinflammatory secretory product of lipopolysaccharide-activated macrophages. Proc Natl Acad Sci USA 89:3511–3515

    Article  PubMed  CAS  Google Scholar 

  • Smart EJ, Ying Y, Donzell WC, Anderson RG (1996) A role for caveolin in transport of cholesterol from endoplasmic reticulumto plasma membrane. J Biol Chem 271:29427–29435

    Article  PubMed  CAS  Google Scholar 

  • Suzuki J, ** ZG, Meoli DF, Matoba T, Berk BC (2006) Cyclophilin A is secreted by a vesicular pathway in vascular smooth muscle cells. Circ Res 98:811–817

    Article  PubMed  CAS  Google Scholar 

  • Takahashi N, Hayano T, Suzuki M (1989) Peptidyl-prolyl cis-trans isomerase is the cyclosporin A-binding protein cyclophilin. Nature 337:473–475

    Article  PubMed  CAS  Google Scholar 

  • Wang P, Heitman J (2005) The cyclophilins. Genome Biol 6:226

    Article  PubMed  Google Scholar 

  • Xu Q, Leiva MC, Fischkoff SA, Handschumacher RE, Lyttle CR (1992) Leukocyte chemotactic activity of cyclophilin. J Biol Chem 267:11968–11971

    PubMed  CAS  Google Scholar 

  • Xu J, Hu X, Kang Y, Wu Z, Chen S, **e Y, Yu X (2004) Construction of full-length gene expression library of Clonorchis sinensis adults and establishment of the gene expression pattern. Chin J Zoonoses 2:383–393

    Google Scholar 

  • Yang H, Chen J, Yang J, Qiao S, Zhao S, Yu L (2007) Cyclophilin A is upregulated in small cell lung cancer and activates ERK1/2 signal. Biochem Biophys Res Commun 361:763–767

    Article  PubMed  CAS  Google Scholar 

  • Yurchenko V, Zybarth G, O'Connor M, Dai WW, Franchin G, Hao T, Guo H, Hung HC, Toole B, Gallay P, Sherry B, Bukrinsky M (2002) Active-site residues of cyclophilin A are crucial for its signaling activity via CD147. J Biol Chem 277:22959–22965

    Article  PubMed  CAS  Google Scholar 

  • Zhu C, Wang X, Deinum J, Huang Z, Gao J, Modjtahedi N, Neagu MR, Nilsson M, Eriksson PS, Hagberg H, Luban J, Kroemer G, Blomgren K (2007) Cyclophilin A participates in the nuclear translocation of apoptosis-inducing factor in neurons after cerebral hypoxia-ischemia. J Exp Med 204:1741–1748

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by China National Great Basic Research Program (973 program, No.2010CB530003) and China National Natural Science Foundation (No.30771887).

Author information

Authors and Affiliations

  1. Zhongshan School of Medicine, Department of Parasitology, Sun Yat-sen University, Guangzhou, People’s Republic of China

    Weihua Wu, Jiajia Chen, Suxiang Zeng, Zhao** Zhang, Wenjia Gan, ** Zhang, Wenjia Gan, **nbing Yu & Xuchu Hu

Authors
  1. Weihua Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jiajia Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Suxiang Zeng
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Zhao** Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Wenjia Gan
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. **nbing Yu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Xuchu Hu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Xuchu Hu.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wu, W., Chen, J., Zeng, S. et al. Molecular cloning, expression, and characterization of cyclophilin A from Clonorchis sinensis . Parasitol Res 109, 345–351 (2011). https://doi.org/10.1007/s00436-011-2262-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00436-011-2262-2

Keywords

Search

Navigation