Generic placeholder image

Current Proteomics

Editor-in-Chief

ISSN (Print): 1570-1646
ISSN (Online): 1875-6247

Research Article

Upregulation of Cathepsin B-like Protease Activity During Apoptosis in Giardia duodenalis

Author(s): Sergio Alonso Durán-Pérez, Héctor Samuel López-Moreno, Maribel Jiménez-Edeza, Jesús Ricardo Parra-Unda, Edgar Rangel-López and José Guadalupe Rendón-Maldonado*

Volume 16, Issue 4, 2019

Page: [330 - 337] Pages: 8

DOI: 10.2174/1570164616666190204112452

Price: $65

Abstract

Background: In eukaryotic cells, apoptosis signaling pathways are controlled mainly by aspartic acid cysteine proteases (caspases). However, certain unicellular microorganisms, such as Giardia duodenalis, lack these proteins. Thus, other cysteine proteases may play an important role in the parasite apoptosis signaling pathway.

Objective: To understand the effect of cathepsin B-like inhibition on the cell viability of Giardia duodenalis and its cell death process.

Methods: Bioinformatics analysis was performed to identify apoptotic proteases. Analysis showed that cathepsin B-like protease genes from G. duodenalis were the best candidate. A homology modeling technique was used to explore in silico the inhibitory effect of E-64 against cathepsin B-like proteases from G. duodenalis genome and to examine the effect of curcumin on cathepsin B-like activity regulation. In addition, the effect of E-64 on parasite survival and DNA fragmentation was tested.

Results: Eight cathepsin B-like protease coding genes were identified in silico. Interestingly, while these sequences lacked the cathepsin B characteristic occluding loop, they maintained the catalytic active- site responsible for cathepsin B activity, which was evidenced by the increase in the degradation of the Z-RR-AMC substrate, suggesting the upregulation of the activity of these proteins. Additionally, inhibition of E-64 against G. duodenalis trophozoites caused a decrease in DNA fragmentation compared to control cells and had a positive effect on parasite survival after exposure to curcumin.

Conclusion: Overall, these results suggested that Giardia duodenalis might have a cell death mechanism in which cathepsin B-like proteases play an important role.

Keywords: Apoptosis-like, cathepsin B-like, Giardia duodenalis, E-64, eukaryotes, infections.

Graphical Abstract
[1]
Quihui-Cota, L.; Morales-Figueroa, G.G. Persistence of intestinal parasitic infections during the national De-worming campaign in schoolchildren of Northwestern Mexico: A cross-sectional study. Ann. Gastroenterol., 2012, 25, 57-60.
[2]
Goyal, N.; Rishi, P.; Shukla, G. Lactobacillus Rhamnosus GG antagonizes giardia intestinalis induced oxidative stress and intestinal disaccharidases: An experimental study. World J. Microbiol. Biotechnol., 2013, 29, 1049-1057.
[3]
Coelho, C.H.; Durigan, M.; Leal, D.A.G.; Schneider, A.B.; Franco, R.M.B.; Singer, S.M. Giardiasis as a neglected disease in Brazil: Systematic review of 20 years of publications. PLoS Negl. Trop. Dis., 2017, 11, e0006005.
[4]
Adam, R.D. Biology of Giardia lamblia. Clin. Microbiol. Rev., 2001, 14, 447-475.
[5]
Lujan, H.D.; Touz, M.C. Protein trafficking in Giardia lamblia. Cell. Microbiol., 2003, 5, 427-434.
[6]
Reece, S.E.; Pollitt, L.C.; Colegrave, N.; Gardner, A. The meaning of death: Evolution and ecology of apoptosis in protozoan parasites. PLoS Pathog., 2011, 7, e1002320.
[7]
Ghosh, E.; Ghosh, A.; Ghosh, A.N.; Nozaki, T.; Ganguly, S. Oxidative stress-induced cell cycle blockage and a protease-independent programmed cell death in microaerophilic giardia lamblia. Drug Des. Devel. Ther., 2009, 3, 103-110.
[8]
Correa, G.; Vilela, R.; Menna-Barreto, R.F.; Midlej, V.; Benchimol, M. Cell death induction in giardia lamblia: Effect of beta-lapachone and starvation. Parasitol. Int., 2009, 58, 424-437.
[9]
Turk, B.; Stoka, V. Protease signalling in cell death: Caspases versus cysteine cathepsins. FEBS Lett., 2007, 581, 2761-2767.
[10]
Repnik, U.; Hafner Cesen, M.; Turk, B. . Lysosomal membrane permeabilization in cell death: Concepts and challenges. Mitochondrion 2014. 19 Pt A, 49-57
[11]
DuBois, K.N.; Abodeely, M.; Sakanari, J.; Craik, C.S.; Lee, M.; McKerrow, J.H.; Sajid, M. Identification of the major cysteine protease of giardia and its role in encystation. J. Biol. Chem., 2008, 283, 18024-18031.
[12]
Ch’ng, J.H.; Kotturi, S.R.; Chong, A.G.; Lear, M.J.; Tan, K.S. A programmed cell death pathway in the malaria parasite Plasmodium falciparum has general features of mammalian apoptosis but is mediated by clan CA cysteine proteases. Cell Death Dis., 2010, 1, e26.
[13]
El-Fadili, A.K.; Zangger, H.; Desponds, C.; Gonzalez, I.J.; Zalila, H.; Schaff, C.; Ives, A.; Masina, S.; Mottram, J.C.; Fasel, N. Cathepsin B-like and cell death in the unicellular human pathogen Leishmania. Cell Death Dis., 2010, 1, e71.
[14]
Johansson, A.C.; Appelqvist, H.; Nilsson, C.; Kagedal, K.; Roberg, K.; Ollinger, K. Regulation of apoptosis-associated lysosomal membrane permeabilization. Apoptosis, 2010, 15, 527-540.
[15]
Chen, Q.Y.; Shi, J.G.; Yao, Q.H.; Jiao, D.M.; Wang, Y.Y.; Hu, H.Z.; Wu, Y.Q.; Song, J.; Yan, J.; Wu, L.J. Lysosomal membrane permeabilization is involved in curcumin-induced apoptosis of A549 lung carcinoma cells. Mol. Cell. Biochem., 2012, 359, 389-398.
[16]
Perez-Arriaga, L.; Mendoza-Magana, M.L.; Cortes-Zarate, R.; Corona-Rivera, A.; Bobadilla-Morales, L.; Troyo-Sanroman, R.; Ramirez-Herrera, M.A. Cytotoxic effect of curcumin on Giardia lamblia trophozoites. Acta Trop., 2006, 98, 152-161.
[17]
de Paula Aguiar, D.; Brunetto Moreira Moscardini, M.; Rezende Morais, E.; Graciano de Paula, R.; Ferreira, P.M.; Afonso, A.; Belo, S.; Tomie Ouchida, A.; Curti, C.; Cunha, W.R.; Rodrigues, V.; Magalhaes, L.G. Curcumin generates oxidative stress and induces apoptosis in adult Schistosoma mansoni worms. PLoS One, 2016, 11, e0167135.
[18]
Nayak, A.; Gayen, P.; Saini, P.; Mukherjee, N.; Babu, S.P. Molecular evidence of curcumin-induced apoptosis in the filarial worm setaria cervi. Parasitol. Res., 2012, 111, 1173-1186.
[19]
Zimmermann, L.; Stephens, A.; Nam, S-Z.; Rau, D.; Kubler, J.; Lozajic, M.; Gabler, F.; Soding, J.; Lupas, A.N.; Alva, V. A completely reimplemented MPI bioinformatics toolkit with a new HHpred server at its core. J. Mol. Biol., 2018, 430, 2237-2243.
[20]
Webb, B.; Sali, A. Comparative protein structure modeling using modeller. Curr. Protoc. Bioinformatics, 2016, 54
[http://dx.doi.org/ Doi:10.1002/ 0471250953.bi0506s15]
[21]
Laskowski, R.A.; MacArthur, M.W.; Moss, D.S.; Thornton, J.M. PROCHECK: A program to check the stereochemical quality of protein structures. J. Appl. Cryst., 1993, 26, 283-291.
[22]
Bowie, J.U.; Luthy, R.; Eisenberg, D. A method to identify protein sequences that fold into a known three-dimensional structure. Science, 1991, 253(5016), 164-170.
[23]
Luthy, R.; Bowie, J.U.; Eisenberg, D. Assessment of protein models with three-dimensional profiles. Nature, 1992, 356, 83-85.
[24]
Wiederstein, M.; Sippl, M.J. ProSA-web: Interactive web service for the recognition of errors in three-dimensional structures of proteins. Nucleic Acids Res., 2007, 35, W407-W410.
[25]
Sippl, M.J. Recognition of errors in three-dimensional structures of proteins. Proteins, 1993, 17, 355-362.
[26]
Zhou, H.; Skolnick, J. FINDSITE(comb): A threading/structure-based, proteomic-scale virtual ligand screening approach. J. Chem. Inf. Model., 2013, 53, 230-240.
[27]
Keister, D.B. Axenic culture of Giardia lamblia in TYI-S-33 medium supplemented with bile. Trans. R. Soc. Trop. Med. Hyg., 1983, 77, 487-488.
[28]
Minina, E.A.; Coll, N.S.; Tuominen, H.; Bozhkov, P.V. Metacaspases versus caspases in development and cell fate regulation. Cell Death Differ., 2017, 24, 1314-1325.
[29]
Artus, C.; Maquarre, E.; Moubarak, R.S.; Delettre, C.; Jasmin, C.; Susin, S.A.; Robert-Lézénès, J. CD44 ligation induces caspase-independent cell death via a novel calpain/AIF pathway in human erythroleukemia cells. Oncogene, 2006, 25, 5741-5751.
[30]
Bagchi, S.; Oniku, A.E.; Topping, K.; Mamhoud, Z.N.; Paget, T.A. Programmed cell death in giardia. Parasitology, 2012, 139, 894-903.
[31]
John, B.; Sali, A. comparative protein structure modeling by iterative alignment, model building and model assessment. Nucleic Acids Res., 2003, 31, 3982-3992.
[32]
Sali, A.; Sali, A. Statistical potential for assessment and prediction of protein structures. Protein Sci., 2006, 15(11), 2507-2524.
[33]
Li, Y.Y.; Fang, J.; Ao, G.Z. Cathepsin B and L inhibitors: A patent review (2010 - present). Expert Opin. Ther. Pat., 2017, 27, 643-656.
[34]
Reich, M.; Wieczerzak, E.; Jankowska, E.; Palesch, D.; Boehm, B.O.; Burster, T. Specific cathepsin B inhibitor is cell-permeable and activates presentation of TTC in primary human dendritic cells. Immunol. Lett., 2009, 123, 155-159.
[35]
Matsumoto, K.; Mizoue, K.; Kitamura, K.; Tse, W.C.; Huber, C.P.; Ishida, T. Structural basis of inhibition of cysteine proteases by E-64 and its derivatives. Biopolymers, 1999, 51, 99-107.
[36]
Mendoza-Palomares, C.; Biteau, N.; Giroud, C.; Coustou, V.; Coetzer, T.; Authie, E.; Boulange, A.; Baltz, T. Molecular and biochemical characterization of a cathepsin B-like protease family unique to Trypanosoma congolense. Eukaryot. Cell, 2008, 7, 684-697.
[37]
Malagon, D.; Diaz-Lopez, M.; Benitez, R.; Adroher, F.J. Cathepsin B- and L-like cysteine protease activities during the in vitro development of Hysterothylacium aduncum (nematoda: Anisakidae), a worldwide fish parasite. Parasitol. Int., 2010, 59, 89-92.
[38]
Vancompernolle, K.; Van Herreweghe, F.; Pynaert, G.; Van de Craen, M.; De Vos, K.; Totty, N.; Sterling, A.; Fiers, W.; Vandenabeele, P.; Grooten, J. Atractyloside-induced release of cathepsin B, a protease with caspase-processing activity. FEBS Lett., 1998, 438, 150-158.
[39]
Rico, E.; Alzate, J.F.; Arias, A.A.; Moreno, D.; Clos, J.; Gago, F.; Moreno, I.; Dominguez, M.; Jimenez-Ruiz, A. Leishmania infantum expresses a mitochondrial nuclease homologous to EndoG that migrates to the nucleus in response to an apoptotic stimulus. Mol. Biochem. Parasitol., 2009, 163, 28-38.
[40]
Cai, Y.M.; Yu, J.; Ge, Y.; Mironov, A.; Gallois, P. Two proteases with caspase-3-like activity, cathepsin B and proteasome, antagonistically control ER-stress-induced programmed cell death in Arabidopsis. New Phytol., 2018, 218, 1143-1155.

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy