دورية أكاديمية
Deubiquitinating enzymes as possible drug targets for schistosomiasis.
| العنوان: | Deubiquitinating enzymes as possible drug targets for schistosomiasis. |
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| المؤلفون: | Barban do Patrocínio A; Medicine Faculty of Ribeirão Preto, University of São Paulo (Department of Biochemistry and Immunology). Avenue Bandeirantes, 3900. Ribeirão Preto (São Paulo), Brazil; CEP 14049-900., Cabral FJ; Institute of Biology, University State of Campinas (Department of Animal Biology). Rua Monteiro Lobato, 255. Campinas (São Paulo) Brazil; CEP 13083-862. Electronic address: fjanku@unicamp.br., de Paiva TH; Institute of Exact and Biological Sciences, Federal University of Ouro Preto, Campus Universitário Morro do Cruzeiro- Bauxita. Ouro Preto (Minas Gerais), Brazil; CEP 35400-000., Magalhães LG; Research Group on Natural Products (Center for Research in Sciences and Technology), University of Franca. Av. Dr. Armando de Sáles Oliveira, 201 - Parque Universitário, Franca (São Paulo), Brazil; CEP 14404-600. Electronic address: lizandra.magalhaes@unifran.edu.br., Paula LAL; Research Group on Natural Products (Center for Research in Sciences and Technology), University of Franca. Av. Dr. Armando de Sáles Oliveira, 201 - Parque Universitário, Franca (São Paulo), Brazil; CEP 14404-600., Brigato OM; Medicine Faculty of Ribeirão Preto, University of São Paulo (Department of Biochemistry and Immunology). Avenue Bandeirantes, 3900. Ribeirão Preto (São Paulo), Brazil; CEP 14049-900. Electronic address: olinda@fmrp.usp.br., Guerra-Sá R; Institute of Exact and Biological Sciences, Federal University of Ouro Preto, Campus Universitário Morro do Cruzeiro- Bauxita. Ouro Preto (Minas Gerais), Brazil; CEP 35400-000., Rodrigues V; Medicine Faculty of Ribeirão Preto, University of São Paulo (Department of Biochemistry and Immunology). Avenue Bandeirantes, 3900. Ribeirão Preto (São Paulo), Brazil; CEP 14049-900. Electronic address: vrodrigu@fmrp.usp.br. |
| المصدر: | Acta tropica [Acta Trop] 2021 May; Vol. 217, pp. 105856. Date of Electronic Publication: 2021 Feb 09. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Country of Publication: Netherlands NLM ID: 0370374 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-6254 (Electronic) Linking ISSN: 0001706X NLM ISO Abbreviation: Acta Trop Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Amsterdam : Elsevier Original Publication: Basel. |
| مواضيع طبية MeSH: | Aminopyridines/*pharmacology , Deubiquitinating Enzymes/*antagonists & inhibitors , Schistosoma mansoni/*drug effects , Schistosomiasis/*drug therapy , Thiocyanates/*pharmacology, Animals ; Apoptosis/drug effects ; Autophagy/drug effects ; Drug Discovery ; Female ; Gene Expression Regulation ; Life Cycle Stages/drug effects ; Male ; Mice ; Mice, Inbred BALB C ; Mitochondria/drug effects ; Mitochondria/ultrastructure ; Movement/drug effects ; Oviposition/drug effects ; Proteasome Endopeptidase Complex/metabolism ; Real-Time Polymerase Chain Reaction ; Schistosoma mansoni/ultrastructure ; Signal Transduction/drug effects ; Transforming Growth Factor beta/metabolism |
| مستخلص: | Deubiquitinating enzymes (DUBs) are conserved in Schistosoma mansoni and may be linked to the 26S proteasome. Previous results from our group showed that b-AP15, an inhibitor of the 26S proteasome DUBs UCHL5 and USP14 induced structural and gene expression changes in mature S. mansoni pairs. This work suggests the use of the nonselective DUB inhibitor PR-619 to verify whether these enzymes are potential target proteins for new drug development. Our approach is based on previous studies with DUB inhibitors in mammalian cells that have shown that these enzymes are associated with apoptosis, autophagy and the transforming growth factor beta (TGF-β) signaling pathway. PR-619 inhibited oviposition in parasite pairs in vitro, leading to mitochondrial changes, autophagic body formation, and changes in expression of SmSmad2 and SmUSP9x, which are genes linked to the TGF-β pathway that are responsible for parasite oviposition and SmUCHL5 and SmRpn11 DUB maintenance. Taken together, these results indicate that DUBs may be used as targets for the development of new drugs against schistosomiasis. (Copyright © 2021. Published by Elsevier B.V.) |
| فهرسة مساهمة: | Keywords: Deubiquitinating enzymes; PR-619 inhibitor; Schistosoma mansoni |
| المشرفين على المادة: | 0 (2,6-diaminopyridine-3,5-bis(thiocyanate)) 0 (Aminopyridines) 0 (Thiocyanates) 0 (Transforming Growth Factor beta) EC 3.4.19.12 (Deubiquitinating Enzymes) EC 3.4.25.1 (Proteasome Endopeptidase Complex) EC 3.4.99.- (ATP dependent 26S protease) |
| تواريخ الأحداث: | Date Created: 20210212 Date Completed: 20210519 Latest Revision: 20210519 |
| رمز التحديث: | 20231215 |
| DOI: | 10.1016/j.actatropica.2021.105856 |
| PMID: | 33577811 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1873-6254 |
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| DOI: | 10.1016/j.actatropica.2021.105856 |