DOI QR코드

DOI QR Code

Prostaglandin synthase activity of sigma- and mu-class glutathione transferases in a parasitic trematode, Clonorchis sinensis

  • Jiyoung Kim (Department of Microbiology, Gachon University College of Medicine) ;
  • Woon-Mok Sohn (Department of Parasitology and Tropical Medicine, and Institute of Health Sciences, Gyeongsang National University College of Medicine) ;
  • Young-An Bae (Department of Microbiology, Gachon University College of Medicine)
  • Received : 2024.01.22
  • Accepted : 2024.03.21
  • Published : 2024.05.31

Abstract

Sigma-class glutathione transferase (GST) proteins with dual GST and prostaglandin synthase (PGS) activities play a crucial role in the establishment of Clonorchis sinensis infection. Herein, we analyzed the structural and enzymatic properties of sigma-class GST (CsGST-σ) proteins to obtain insight into their antioxidant and immunomodulatory functions in comparison with mu-class GST (CsGST-µ) proteins. CsGST-σ proteins conserved characteristic structures, which had been described in mammalian hematopoietic prostaglandin D2 synthases. Recombinant forms of these CsGST-σ and CsGST-µ proteins expressed in Escherichia coli exhibited considerable degrees of GST and PGS activities with substantially different specific activities. All recombinant proteins displayed higher affinities toward prostaglandin H2 (PGS substrate; average Km of 30.7 and 3.0 ㎛ for prostaglandin D2 [PGDS] and E2 synthase [PGES], respectively) than those toward CDNB (GST substrate; average Km of 1,205.1 ㎛). Furthermore, the catalytic efficiency (Kcat/Km) of the PGDS/PGES activity was higher than that of GST activity (average Kcat/Km of 3.1, 0.7, and 7.0×10-3 s-1-1 for PGDS, PGES, and GST, respectively). Our data strongly suggest that the C. sinensis sigma- and mu-class GST proteins are deeply involved in regulating host immune responses by generating PGD2 and PGE2 in addition to their roles in general detoxification.

Keywords

Acknowledgement

This work was supported by the Basic Science Research Programs of the National Research Foundation of Korea (NRF), funded by the Ministry of Education (NRF-2017R1D1A1B03028355) and by the Gachon University research fund of 2018 (GCU-2018-0329) to YAB.

References

  1. Armstrong RN. Structure, catalytic mechanism, and evolution of the glutathione transferases. Chem Res Toxicol 2003;10(1):2-18. https://doi.org/10.1021/tx960072x
  2. Bartling D, Radzio R, Steiner U, Weiler EW. A glutathione-S-transferase with glutathione-peroxidase activity from Arabidopsis thaliana - molecular cloning and functional characterization. Eur J Biochem 1993;216(2):579-586. https://doi.org/10.1111/j.1432-1033.1993.tb18177.x
  3. Fernandez-Canon JM, Penalva MA. Characterization of a fungal maleylacetoacetate isomerase gene and identification of its human homologue. J Biol Chem 1998;273(1):329-337. https://doi.org/10.1074/jbc.273.1.329
  4. Kim JG, Kang I, Ahn CS, Sohn WM, Kong Y. Omega-class glutathione transferases protect DNA from oxidative stress in pathogenic helminth reproductive cells. Antioxidants 2023;12(3):560. http://doi:10.3390/antiox12030560
  5. Jowsey IR, Thomson AM, Flanagan JU, Murdock PR, Moore GB, et al. Mammalian class sigma glutathione S-transferases: catalytic properties and tissue-specific expression of human and rat GSH-dependent prostaglandin D2 synthase. Biochem J 2001;359(Pt 3):507-516. https://doi.org/10.1042/0264-6021:3590507
  6. Hayes JD, Flanagan JU, Jowsey IR. Glutathione transferases. Annu Rev Pharmacol Toxicol 2005;45:51-88. https://doi.org/10.1146/annurev.pharmtox.45.120403.095857
  7. Chemale G, Morphew R, Moxon JV, Morassuti AL, Lacourse EJ, et al. Proteomic analysis of glutathione transferases from the liver fluke parasite, Fasciola hepatica. Proteomics 2006;6(23):6263-6273. https://doi.org/10.1002/pmic.200600499
  8. Morphew RM, Eccleston N, Wilkinson TJ, McGarry J, Perally S, et al. Proteomics and in silico approaches to extend understanding of the glutathione transferase superfamily of the tropical liver fluke Fasciola gigantica. J Proteome Res 2012;11(12):5876-5889. https://doi.org/10.1021/pr300654w
  9. Bae YA, Ahn DW, Lee EG, Kim SH, Cai GB, et al. Differential activation of diverse glutathione transferases of Clonorchis sinensis in response to the host bile and oxidative stressors. PLoS Negl Trop Dis 2013;7(5):e2211. https://doi.org/10.1371/journal.pntd.0002211
  10. Ricciotti E, FitzGerald GA. Prostaglandins and inflammation. Arterioscler Thromb Vasc Biol 2011;31(5):986-1000. https://doi.org/10.1161/ATVBAHA.110.207449
  11. Joo M, Sadikot RT. PGD synthase and PGD2 in immune response. Mediators Inflamm 2012;2012:503128. https://doi.org/10.1155/2012/503128
  12. Inoue T, Irikura D, Okazaki N, Kinugasa S, Matsumura H, et al. Mechanism of metal activation of human hematopoietic prostaglandin D synthase. Nat Struct Biol 2003;10(4):291-296. https://doi.org/10.1038/nsb907
  13. Kanaoka Y, Fujimori K, Kikuno R, Sakaguchi Y, Urade Y, et al. Structure and chromosomal localization of human and mouse genes for hematopoietic prostaglandin D synthase. Conservation of the ancestral genomic structure of sigma-class glutathione S-transferase. Eur J Biochem 2000;267(11):3315-3322. https://doi.org/10.1046/j.1432-1327.2000.01362.x
  14. Kubata BK, Duszenko M, Martin KS, Urade Y. Molecular basis for prostaglandin production in hosts and parasites. Trends Parasitol 2007;23(7):325-331. https://doi.org/10.1016/j.pt.2007.05.005
  15. Sommer A, Rickert R, Fischer P, Steinhart H, Walter RD, et al. A dominant role for extracellular glutathione S-transferase from Onchocerca volvulus is the production of prostaglandin D2. Infect Immun 2003;71(6):3603-3606. https://doi.org/10.1128/IAI.71.6.3603-3606.2003
  16. Johnson KA, Angelucci F, Bellelli A, Herve M, Fontaine J, et al. Crystal structure of the 28 kDa glutathione S-transferase from Schistosoma haematobium. Biochemistry 2003;42(34):10084-10094. https://doi.org/10.1021/bi034449r
  17. LaCourse EJ, Perally P, Morphew RM, Moxon JV, Prescott M, et al. The sigma class glutathione transferase from the liver fluke Fasciola hepatica. PLoS Negl Trop Dis 2012;6(5):e1666. https://doi.org/10.1371/journal.pntd.0001666
  18. Gourbal BE, Guillou F, Mitta G, Sibille P, Theron A, et al. Excretory-secretory products of larval Fasciola hepatica investigated using a two-dimensional proteomic approach. Mol Biochem Parasitol 2008;161(1):63-66. https://doi.org/10.1016/j.molbiopara.2008.05.002
  19. Mulvenna J, Sripa B, Brindley PJ, Gorman J, Jones MK, et al. The secreted and surface proteomes of the adult stage of the carcinogenic human liver fluke Opisthorchis viverrini. Proteomics 2010;10(5):1063-1078. https://doi.org/10.1002/pmic.200900393
  20. Jefferies JR, Campbell AM, van Rossum AJ, Barrett J, Brophy PM. Proteomic analysis of Fasciola hepatica excretory-secretory products. Proteomics 2001;1(9):1128-1132. https://doi.org/10.1002/1615-9861(200109)1:9<1128::AID-PROT1128>3.0.CO;2-0
  21. Morphew RM, Wright HA, LaCourse EJ, Woods DJ, Brophy PM. Comparative proteomics of excretory-secretory proteins released by the liver fluke Fasciola hepatica in sheep host bile and during in vitro culture ex host. Mol Cell Proteomics 2007; 6(6):963-972. https://doi.org/10.1074/mcp.M600375-MCP200
  22. Lun, ZR, Gasser RB, Lai DH, Li AX, Zhu XQ, et al. Clonorchiasis: a key foodborne zoonosis in China. Lancet Infect Dis 2005;5(1):31-41. https://doi.org/10.1016/S1473-3099(04)01252-6
  23. Shin HR, Oh JK, Masuyer E, Curado MP, Bouvard V, et al. Epidemiology of cholangiocarcinoma: an update focusing on risk factors. Cancer Sci 2010;101(3):579-585. https://doi.org/10.1111/j.1349-7006.2009.01458.x
  24. Koda S, Zhu XQ, Zheng KY, Yan C. Molecular mechanisms of Clonorchis sinensis-host interactions and implications for vaccine development. Front Cell Dev Biol 2022:9:781768. https://doi.org/10.3389/fcell.2021.781768
  25. Oyesola OO, Wojno EDT. Prostaglandin regulation of type 2 inflammation: from basic biology to therapeutic interventions. Eur J Immunol 2021;51(10):2399-2416. https://doi.org/10.1002/eji.202048909
  26. Bae YA, Kim JG, Kong Y. Phylogenetic characterization of Clonorchis sinensis proteins homologous to the sigma-class glutathione transferase and their differential expression profiles. Mol Biochem Parasitol 2016;206(1-2):46-55. https://doi.org/10.1016/j.molbiopara.2016.01.002
  27. de Smith AJ, Walters RG, Froguel P, Blakemore AI. Human genes involve in copy number variation: mechanisms of origin, functional effects and implications for disease. Cytogenet Genome Res 2008;123(1-4):17-26. https://doi.org/10.1159/000184688
  28. L'vova MN, Duzhak TG, Tsentalovich IuP, Katokhin AV, Mordvinov VA. Secretome of the adult liver fluke Opisthorchis felineus. Parazitologiia 2014;48(3):169-184 (in Russian).
  29. Hong ST, Kho WG, Kim WH, Chai JY, Lee SH. Turnover of biliary epithelial cells in Clonorchis sinensis infected rats. Parasites Hosts Dis 1993;31(2):83-89. https://doi.org/10.3347/kjp.1993.31.2.83
  30. Robinson MW, Menon R, Donnelly SM, Dalton JP, Ranganathan S. An integrated transcriptomic and proteomics analysis of the secretome of the helminth pathogen Fasciola hepatica: proteins associated with invasion and infection of the mammalian host. Mol Cell Proteomics 2009;8(8):1891-1907. https://doi.org/10.1074/mcp.M900045-MCP200
  31. Angeli V, Faveeuw C, Roye O, Fontaine J, Teissier E, et al. Role of the parasite-derived prostaglandin D2 in the inhibition of epidermal Langerhans cell migration during schistosomiasis infection. J Exp Med 2001;193(10):1135-1147. https://doi.org/10.1084/jem.193.10.1135
  32. Pakharukova MY, Zaparina OG, Kovner AV, Mordvinov VA. Inhibition of Opisthorchis felineus glutathione-dependent prostaglandin synthase by resveratrol correlates with attenuation of cholangiocyte neoplasia in a hamster model of opisthorchiasis. Int J Parasitol 2019;49(12):963-973. https://doi.org/10.1016/j.ijpara.2019.07.002
  33. Fusco AC, Salafsky B, Delbrook K. Schistosoma mansoni: production of cercarial eicosanoids as correlates of penetration and transformation. J Parasitol 1986;72(3):397-404. https://doi.org/10.2307/3281679
  34. Maeng S, Lee HW, Bashir Q, Kim TI, Hong SJ, et al. Oxidative stress-mediated mouse liver lesions caused by Clonorchis sinensis infection. Int J Parasitol 2016;46(3):195-204. https://doi.org/10.1016/j.ijpara.2015.11.003
  35. Ahn CS, Kim JG, Kang I, Kong Y. Omega-class glutathione transferases of carcinogenic liver fluke, Clonorchis sinensis, modulate apoptosis and differentiation of host cholangiocytes. Antioxidants (Basel) 2021;10(7):1017. https://doi.org/10.3390/antiox10071017
  36. Beuckmann CT, Fujimori K, Urade Y, Hayaishi O. Identification of mu-class glutathione transferases M2-2 and M3-3 as cytosolic prostaglandin E synthases in the human brain. Neurochem Res 2000;25(5):733-738. https://doi.org/10.1023/a:1007579507804