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A proteasomal β5 subunit of Haemonchus contortus with a role in the growth, development and life span

BACKGROUND: The proteasome in eukaryotic cells can degrade a variety of proteins and plays an important role in regulating the cell cycle, cell survival and apoptosis. The proteasome receives much attention as a potential chemotherapeutic target for treatment of a variety of infectious parasitic dis...

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Autores principales: He, Li, Zhang, Hong-Run, Di, Wen-Da, Li, Fang-Fang, Wang, Chun-Qun, Yang, Xin, Liu, Xiao-Fang, Hu, Min
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10015785/
https://www.ncbi.nlm.nih.gov/pubmed/36922877
http://dx.doi.org/10.1186/s13071-023-05676-6
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author He, Li
Zhang, Hong-Run
Di, Wen-Da
Li, Fang-Fang
Wang, Chun-Qun
Yang, Xin
Liu, Xiao-Fang
Hu, Min
author_facet He, Li
Zhang, Hong-Run
Di, Wen-Da
Li, Fang-Fang
Wang, Chun-Qun
Yang, Xin
Liu, Xiao-Fang
Hu, Min
author_sort He, Li
collection PubMed
description BACKGROUND: The proteasome in eukaryotic cells can degrade a variety of proteins and plays an important role in regulating the cell cycle, cell survival and apoptosis. The proteasome receives much attention as a potential chemotherapeutic target for treatment of a variety of infectious parasitic diseases, but few studies of proteasomes have been done on parasitic nematodes. METHODS: A proteasomal β5 subunit encoding gene (named Hc-pbs-5) and its inferred product (Hc-PBS-5) in Haemonchus contortus were identified and characterized in this study. Then, the transcriptional profiles and anatomical expression were studied using an integrated molecular approach. Finally, a specific proteasome inhibitor bortezomib (BTZ), together with RNA interference (RNAi), was employed to assess the function of Hc-PBS-5. RESULTS: Bioinformatic analysis revealed that the coding sequence of Hc-pbs-5 was 855 bp long and encoded 284 amino acids (aa). The predicted protein (Hc-PBS-5) had core conservative sequences (65–250 aa) belonging to N-terminal nucleophile (Ntn) family of hydrolases. Real-time PCR results revealed that Hc-pbs-5 was continuously transcribed in eight developmental stages with higher levels at the infective third-stage larvae (L3s) and adult males of H. contortus. Immunohistochemical results revealed that Hc-PBS-5 was expressed in intestine, outer cuticle, muscle cells under the outer cuticle, cervical glands and seminal vesicles of male adults and also in intestine, outer cuticle, cervical glands, uterine wall, eggs and ovaries of female adults of H. contortus. BTZ could reduce proportions of egg hatching, and the fourth-stage larvae (L4s) developed from the exsheathed L3s (xL3s) of H. contortus. In addition, silencing Hc-pbs-5 by soaking the specific double-stranded RNA (dsRNA) could decrease the transcription of Hc-pbs-5 and result in fewer xL3s developing to L4s in vitro. CONCLUSIONS: These results indicate that proteasomal β5 subunit plays an important role in the growth, development and life span of H. contortus. GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13071-023-05676-6.
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spelling pubmed-100157852023-03-16 A proteasomal β5 subunit of Haemonchus contortus with a role in the growth, development and life span He, Li Zhang, Hong-Run Di, Wen-Da Li, Fang-Fang Wang, Chun-Qun Yang, Xin Liu, Xiao-Fang Hu, Min Parasit Vectors Research BACKGROUND: The proteasome in eukaryotic cells can degrade a variety of proteins and plays an important role in regulating the cell cycle, cell survival and apoptosis. The proteasome receives much attention as a potential chemotherapeutic target for treatment of a variety of infectious parasitic diseases, but few studies of proteasomes have been done on parasitic nematodes. METHODS: A proteasomal β5 subunit encoding gene (named Hc-pbs-5) and its inferred product (Hc-PBS-5) in Haemonchus contortus were identified and characterized in this study. Then, the transcriptional profiles and anatomical expression were studied using an integrated molecular approach. Finally, a specific proteasome inhibitor bortezomib (BTZ), together with RNA interference (RNAi), was employed to assess the function of Hc-PBS-5. RESULTS: Bioinformatic analysis revealed that the coding sequence of Hc-pbs-5 was 855 bp long and encoded 284 amino acids (aa). The predicted protein (Hc-PBS-5) had core conservative sequences (65–250 aa) belonging to N-terminal nucleophile (Ntn) family of hydrolases. Real-time PCR results revealed that Hc-pbs-5 was continuously transcribed in eight developmental stages with higher levels at the infective third-stage larvae (L3s) and adult males of H. contortus. Immunohistochemical results revealed that Hc-PBS-5 was expressed in intestine, outer cuticle, muscle cells under the outer cuticle, cervical glands and seminal vesicles of male adults and also in intestine, outer cuticle, cervical glands, uterine wall, eggs and ovaries of female adults of H. contortus. BTZ could reduce proportions of egg hatching, and the fourth-stage larvae (L4s) developed from the exsheathed L3s (xL3s) of H. contortus. In addition, silencing Hc-pbs-5 by soaking the specific double-stranded RNA (dsRNA) could decrease the transcription of Hc-pbs-5 and result in fewer xL3s developing to L4s in vitro. CONCLUSIONS: These results indicate that proteasomal β5 subunit plays an important role in the growth, development and life span of H. contortus. GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13071-023-05676-6. BioMed Central 2023-03-15 /pmc/articles/PMC10015785/ /pubmed/36922877 http://dx.doi.org/10.1186/s13071-023-05676-6 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
He, Li
Zhang, Hong-Run
Di, Wen-Da
Li, Fang-Fang
Wang, Chun-Qun
Yang, Xin
Liu, Xiao-Fang
Hu, Min
A proteasomal β5 subunit of Haemonchus contortus with a role in the growth, development and life span
title A proteasomal β5 subunit of Haemonchus contortus with a role in the growth, development and life span
title_full A proteasomal β5 subunit of Haemonchus contortus with a role in the growth, development and life span
title_fullStr A proteasomal β5 subunit of Haemonchus contortus with a role in the growth, development and life span
title_full_unstemmed A proteasomal β5 subunit of Haemonchus contortus with a role in the growth, development and life span
title_short A proteasomal β5 subunit of Haemonchus contortus with a role in the growth, development and life span
title_sort proteasomal β5 subunit of haemonchus contortus with a role in the growth, development and life span
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10015785/
https://www.ncbi.nlm.nih.gov/pubmed/36922877
http://dx.doi.org/10.1186/s13071-023-05676-6
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