دورية أكاديمية
Inhibition of 19S proteasome deubiquitinating activity in Schistosoma mansoni affects viability, oviposition, and structural changes.
| العنوان: | Inhibition of 19S proteasome deubiquitinating activity in Schistosoma mansoni affects viability, oviposition, and structural changes. |
|---|---|
| المؤلفون: | do Patrocinio AB; Departamento de Bioquímica e Imunologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, São Paulo, Brasil. abarbandopatrocinio@gmail.com., Cabral FJ; Departamento de Biologia Animal, Instituto de Biologia, Universidade de Campinas, Campinas, São Paulo, Brasil., Bitencourt ALB; Departamento de Bioquímica e Imunologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, São Paulo, Brasil., Brigato OM; Departamento de Bioquímica e Imunologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, São Paulo, Brasil., Magalhães LG; Núcleo de Pesquisa em Ciências Exatas e Tecnológicas, Universidade de Franca, Franca, Brazil., de Lima Paula LA; Núcleo de Pesquisa em Ciências Exatas e Tecnológicas, Universidade de Franca, Franca, Brazil., Franco L; Departamento de Biologia Animal, Instituto de Biologia, Universidade de Campinas, Campinas, São Paulo, Brasil., Guerra-Sá And R; Núcleo de Pesquisas em Ciências Biológicas, Universidade Federal de Ouro Preto, Morro do Cruzeiro, Ouro Preto, MG, Brasil. rguerra@gmail.com., Rodrigues V; Departamento de Bioquímica e Imunologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, São Paulo, Brasil. |
| المصدر: | Parasitology research [Parasitol Res] 2020 Jul; Vol. 119 (7), pp. 2159-2176. Date of Electronic Publication: 2020 May 19. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Springer International Country of Publication: Germany NLM ID: 8703571 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1432-1955 (Electronic) Linking ISSN: 09320113 NLM ISO Abbreviation: Parasitol Res Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Berlin : Springer International, c1987- |
| مواضيع طبية MeSH: | Deubiquitinating Enzymes/*antagonists & inhibitors , Oviposition/*drug effects , Proteasome Inhibitors/*pharmacology , Schistosoma mansoni/*drug effects, Animals ; Female ; Helminth Proteins/metabolism ; Piperidones/pharmacology ; Proteasome Endopeptidase Complex/metabolism ; Schistosoma mansoni/metabolism ; Schistosoma mansoni/physiology ; Ubiquitination/drug effects |
| مستخلص: | The proteasome is the key player in the cellular protein degradation machinery and is pivotal for protein homeostasis and Schistosoma mansoni (S. mansoni) survival. Our group study provides insights into proteasome inhibitors and reveals that selective schistosomiasis agents represent an interesting branch of proteasome research linked to the development of new drugs for this neglected disease. Here, we explored the phenotypic response of S. mansoni to b-AP15, a bis-benzylidine piperidone that inhibits 26S proteasome deubiquitinases (DUBs), ubiquitin-specific protease 14 (USP14), and ubiquitin carboxyl-terminal hydrolase 5 (UCHL5). b-AP15 induces a modest decrease in egg production in vitro and reduces viability, leading to the death of parasite couples. This inhibitor also induces a twofold increase in the accumulation of polyubiquitinated proteins in S. mansoni adult worms and causes tegument changes such as disintegration, wrinkling, and bubble formation, both throughout the length of the parasite and in the oral sucker. b-AP15 alters the cell organelles of adult S. mansoni worms, and we specifically observed mitochondrial alterations, which are suggestive of proteotoxic stress leading to autophagy. Taken together, these results indicate that the deubiquitinase function of the proteasome is essential for the parasite and support the hypothesis that the proteasome constitutes an interesting drug target for the treatment of schistosomiasis. |
| فهرسة مساهمة: | Keywords: 26S proteasome; Deubiquitinating enzymes; Schistosoma mansoni; b-AP15 inhibitor |
| المشرفين على المادة: | 0 (3,5-bis((4-nitrophenyl)methylidene)-1-prop-2-enoylpiperidin-4-one) 0 (Helminth Proteins) 0 (Piperidones) 0 (Proteasome Inhibitors) EC 3.4.19.12 (Deubiquitinating Enzymes) EC 3.4.25.1 (Proteasome Endopeptidase Complex) |
| تواريخ الأحداث: | Date Created: 20200520 Date Completed: 20200908 Latest Revision: 20200908 |
| رمز التحديث: | 20221213 |
| DOI: | 10.1007/s00436-020-06686-4 |
| PMID: | 32424554 |
| قاعدة البيانات: | MEDLINE |
Find this article in full text from Springer Verlag. 
Full Text Finder كن أول من يترك تعليقا!