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

[ Vol. 16 , Issue. 4 ]

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*   Pages 330 - 337 ( 8 )

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.

Method: 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.

Affiliation:

Doctorado en Biotecnologia, Facultad de Ciencias Quimico Biologicas, Universidad Autonoma de Sinaloa, Calzada de las Americas Norte 2771, Burocrata, 80030 Culiacan, Sinaloa, Doctorado en Biotecnologia, Facultad de Ciencias Quimico Biologicas, Universidad Autonoma de Sinaloa, Calzada de las Americas Norte 2771, Burocrata, 80030 Culiacan, Sinaloa, 1bDoctorado en Ciencias Biomedicas, Facultad de Ciencias Quimico Biologicas, Universidad Autonoma de Sinaloa, Calzada de las Americas Norte 2771, Burocrata, 80030 Culiacan, Sinaloa, Doctorado en Biotecnologia, Facultad de Ciencias Quimico Biologicas, Universidad Autonoma de Sinaloa, Calzada de las Americas Norte 2771, Burocrata, 80030 Culiacan, Sinaloa, Laboratorio de Aminoacidos Excitadores, Instituto Nacional de Neurologia y Neurocirugia Manuel Velasco Suarez, Insurgentes Sur 3877, 14269, Ciudad de Mexico, Doctorado en Biotecnologia, Facultad de Ciencias Quimico Biologicas, Universidad Autonoma de Sinaloa, Calzada de las Americas Norte 2771, Burocrata, 80030 Culiacan, Sinaloa



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