The Effect of Alpha-Tocopherol on the Expression of Epidermal Growth Factor Receptor and Transforming Growth Factor Beta Genes in Three Developmental Stages of Echinococcus granulosus
Background: In recent decades platyhelminths have been used as model organisms to address some of the fundamental questions related to the growth and development of animal organisms. Epidermal Growth Factor Receptors (EGFR) and Transforming Growth Factor beta (TGF-beta) have a regulatory role in the growth and development of Echinococcus species. This study determined the effect of alpha-tocopherol on the expression of EGFR and TGF-beta genes in three in vitro developmental stages of E. granulosus.
Methods: E. granulosus protoscoleces were cultured in diphasic medium containing bovine serum and CMRL 1066. Three developmental stages of E. granulosus, i.e. invaginated protoscoleces, evaginated protoscoleces and three-proglottid worms, were treated by alpha-tocopherol (250 μg/ml for 36 h) and the expression of EGFR and TGF-beta genes were evaluated by using qPCR analysis.
Results: Intact protoscoleces were successfully developed to the segmented worms in diphasic culture media. Higher levels of both EGFR and TGF-beta gene expression were observed in the invaginated protoscoleces as well as the segmented worms in comparison to the non-treated controls.
Conclusion: Administration of alpha-tocopherol to different developmental stages of E. granulosus significantly enhanced EGFR and TGF-beta expression in the parasite. Both oxidant and non-oxidant activities of alpha-tocopherol could explain the study findings. Overexpression of the genes could in turn enhance growth factor effects and facilitates the viability of the parasite.
2. Willms K, Zurabian R. Taenia crassiceps: in vivo and in vitro models. Parasitology. 2010;137(3):335-46.
3. Flisser A, Avila G, Maravilla P, et al. Taenia solium: current understanding of laboratory animal models of taeniosis. Parasitology. 2010;137(3):347-57.
4. McKay DM. The immune response to and im-munomodulation by Hymenolepis diminuta. Parasitolo-gy. 2010;137(3):385-94.
5. Alvarez JI, Mishra BB, Gundra UM, et al. Mesoces-toides corti intracranial infection as a murine model for neurocysticercosis. Parasitology. 2010;137(3):359-72.
6. Valizadeh, M., B. Haghpanah, A. Badirzadeh, et al. Immunization of sheep against Echinococcus granulosus with protoscolex tegumental surface antigens. Vet World. 2017; 10(8): 854-858.
7. Cheng Z, Liu F, Li X, et al. EGF-mediated EGFR/ERK signaling pathway promotes germina-tive cell proliferation in Echinococcus multilocularis that contributes to larval growth and development. Plos Neg Trop Dis. 2017;11(2): e0005418.
8. Konrad C, Kroner A, Spiliotis M, et al. Identifica-tion and molecular characterisation of a gene en-coding a member of the insulin receptor family in Echinococcus multilocularis. Int J Parasitol. 2003;33(3):301-12.
9. Adalid-Peralta L, Rosas G, Arce-Sillas A, et al. Ef-fect of transforming growth factor-β upon taenia so-lium and Taenia crassiceps Cysticerci. Sci Rep. 2017;7(1):12345.
10. Osman A, Niles EG, Verjovski-Almeida S, et al. Schistosoma mansoni TGF-β receptor II: role in host ligand-induced regulation of a schistosome target gene. PloS Pathog. 2006;2(6): e54.
11. Vicogne J, Cailliau K, Tulasne D, et al. Conservation of epidermal growth factor receptor function in the human parasitic helminth Schistosoma mansoni. J Biol Chem. 2004; 279(36):37407-14.
12. Ernst I, Pallauf K, Bendall J, et al. Vitamin E sup-plementation and lifespan in model organisms. Ageing Res Rev. 2013;12(1):365-75.
13. Wang X, Quinn PJ. Vitamin E and its function in membranes. Prog Lipid Res. 1999;38(4):309-36.
14. Fusi E, Rebucci R, Pecorini C, et al. Alpha-tocopherol counteracts the cytotoxicity induced by ochratoxin a in primary porcine fibroblasts. Toxins. 2010;2(6):1265-78.
15. Traber MG, Atkinson J. Vitamin E, antioxidant and nothing more. Free Radical Bio Med. 2007;43(1):4-15.
16. Azzi A, Gysin R, KempnÁ P, et al. Vitamin E me-diates cell signaling and regulation of gene expres-sion. Ann N Y Acad Sci. 2005; 1031(1):86-95.
17. Rimbach G, Minihane AM, Majewicz J, et al. Regu-lation of cell signalling by vitamin E. P Nutr Soc. 2002;61(4):415-25.
18. Khanna S, Roy S, Ryu H, et al. Molecular basis of vitamin E action tocotrienol modulates 12-lipoxygenase, a key mediator of glutamate-induced neurodegeneration. J Biol Chem. 2003;278(44):43508-15.
19. Smyth J, Howkins A, Barton M. Factors controlling the differentiation of the hydatid organism, Echino-coccus granulosus, into cystic or strobilar stages in vitro. Nature. 1966; 211:1374-7.
20. Smyth J, Davies Z. In vitro culture of the strobilar stage of Echinococcus granulosus (sheep strain): a review of basic problems and results. Int J Parasitol. 1974;4(6):631-44.
21. Thompson R, Jenkins D. Echinococcus as a model system: biology and epidemiology. Int J Parasitol. 2014;44(12):865-77.
22. Smyth J, Barrett N. Procedures for testing the via-bility of human hydatid cysts following surgical re-moval, especially after chemotherapy. Trans R Soc Trop Med Hyg. 1980;74(5):649-52.
23. Mohammadzadeh T, Sadjjadi S, Rahimi H, et al. Establishment of a modified in vitro cultivation of protoscoleces to adult Echinococcus granulosus; an im-portant way for new investigations on hydatidosis. Iran J Parasitol. 2012;7(1):59-66.
24. Mousavi SM, Afgar A, Mohammadi MA, et al. Calmodulin-specific small interfering RNA induces consistent expression suppression and morphologi-cal changes in Echinococcus granulosus. Sci Rep. 2019;9(1):3894.
25. Matini, M., M. Roostaei, M. Fallah, et al. Genetic identification of Echinococcus granulosus isolates in Hamadan, Western Iran. Iran J Parasitol. 2018;13(3): 423-429.
26. Hajialilo E, Harandi MF, Sharbatkhori M, et al. Ge-netic characterization of Echinococcus granulosus in camels, cattle and sheep from the south-east of Iran indicates the presence of the G3 genotype. J Hel-minthol. 2012;86(3):263-70.
27. Azzi A, Ricciarelli R, Zingg J-M. Non‐antioxidant molecular functions of α‐tocopherol (vitamin E). FEBS Lett. 2002;519(1-3):8-10.
28. Tasanarong A, Kongkham S, Duangchana S, et al. Vitamin E ameliorates renal fibrosis by inhibition of TGF-beta/Smad2/3 signaling pathway in UUO mice. J Med Assoc Thai. 2011;94: S1-9.
29. Wu K, Liu BH, Zhao DY, et al. Effect of vitamin E succinate on expression of TGF-β1, c-Jun and JNK1 in human gastric cancer SGC-7901 cells. World J Gastroenterol. 2001;7(1):83-87.
30. Yiang GT, Chen JN, Lin PS, et al. Combined treatment with vitamin E and gefitinib has synergis-tic effects to inhibit TGF-β1-induced renal fibro-blast proliferation. Mol Med Rep. 2016;13(6):5372-8.
31. Azzi A, Gysin R, Kempná P, et al. Regulation of gene expression by α-tocopherol. Biol Chem. 2004;385(7):585-91.
32. Brehm K, Spiliotis M. The influence of host hor-mones and cytokines on Echinococcus multilocularis signalling and development. Parasite. 2008, 15(3):286-90.
33. Sussmann RA, Fotoran WL, Kimura EA, et al. Plasmodium falciparum uses vitamin E to avoid oxida-tive stress. Parasite Vector. 2017;10(1):461.
34. Kıvanç I, Celik BA, Karakoc Z, et al. Oxi-dant/Antioxidant Status, PON1 and ARES Activi-ties, Trace Element Levels, and Histological Altera-tions in Sheep with Cystic Echinococcosis. Iran J Parasitol. 2018;13(3):448-456.
35. Dezaki ES, Yaghoubi MM, Spiliotis M, et al. Com-parison of ex vivo harvested and in vitro cultured materials from Echinococcus granulosus by measuring expression levels of five genes putatively involved in the development and maturation of adult worms. Parasitol Res. 2016;115(11):4405-16.
36. Dezaki ES, Yaghoobi MM, Taheri E, et al. Differ-ential Expression of Hox and Notch Genes in Lar-val and Adult Stages of Echinococcus granulosus. Kore-an J Parasitol. 2016; 54(5):653-658.
|Issue||Vol 15 No 2 (2020)|
|Alpha-tocopherol; In vitro Hydatid disease Epidermal growth factor receptor (EGFR) Transforming growth factor-beta (TGF- β)|
|Rights and permissions|
|This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.|