Possible Involvement of Hsp90 in the Regulation of Telomere Length and Telomerase Activity During the Leishmania amazonensis Developmental Cycle and Population Proliferation

Detalhes bibliográficos
Autor(a) principal: de Oliveira, Beatriz C. D. [UNESP]
Data de Publicação: 2021
Outros Autores: Shiburah, Mark E. [UNESP], Paiva, Stepany C. [UNESP], Vieira, Marina R. [UNESP], Morea, Edna Gicela O. [UNESP], da Silva, Marcelo Santos [UNESP], Alves, Cristiane de Santis [UNESP], Segatto, Marcela, Gutierrez-Rodrigues, Fernanda, Borges, Júlio C., Calado, Rodrigo T., Cano, Maria Isabel N. [UNESP]
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da UNESP
Texto Completo: http://dx.doi.org/10.3389/fcell.2021.713415
http://hdl.handle.net/11449/222849
Resumo: The Leishmania developmental cycle comprises three main life forms in two hosts, indicating that the parasite is continually challenged due to drastic environmental changes. The disruption of this cycle is critical for discovering new therapies to eradicate leishmaniasis, a neglected disease that affects millions worldwide. Telomeres, the physical ends of chromosomes, maintain genome stability and cell proliferation and are potential antiparasitic drug targets. Therefore, understanding how telomere length is regulated during parasite development is vital. Here, we show that telomeres form clusters spread in the nucleoplasm of the three parasite life forms. We also observed that amastigotes telomeres are shorter than metacyclic and procyclic promastigotes and that in parasites with continuous in vitro passages, telomere length increases over time. These observed differences in telomere length among parasite’s life stages were not due to lack/inhibition of telomerase since enzyme activity was detected in all parasite life stages, although the catalysis was temperature-dependent. These data led us to test if, similar to other eukaryotes, parasite telomere length maintenance could be regulated by Hsp83, the ortholog of Hsp90 in trypanosomatids, and Leishmania (LHsp90). Parasites were then treated with the Hsp90 inhibitor 17AAG. The results showed that 17AAG disturbed parasite growth, induced accumulation into G2/M phases, and telomere shortening in a time-dependent manner. It has also inhibited procyclic promastigote’s telomerase activity. Besides, LHsp90 interacts with the telomerase TERT component as shown by immunoprecipitation, strongly suggesting a new role for LHsp90 as a parasite telomerase component involved in controlling telomere length maintenance and parasite life span.
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spelling Possible Involvement of Hsp90 in the Regulation of Telomere Length and Telomerase Activity During the Leishmania amazonensis Developmental Cycle and Population Proliferationcontinuous in vitro passagesLeishmania life formsLHsp90telomerase ribonucleoprotein complextelomeres maintenanceThe Leishmania developmental cycle comprises three main life forms in two hosts, indicating that the parasite is continually challenged due to drastic environmental changes. The disruption of this cycle is critical for discovering new therapies to eradicate leishmaniasis, a neglected disease that affects millions worldwide. Telomeres, the physical ends of chromosomes, maintain genome stability and cell proliferation and are potential antiparasitic drug targets. Therefore, understanding how telomere length is regulated during parasite development is vital. Here, we show that telomeres form clusters spread in the nucleoplasm of the three parasite life forms. We also observed that amastigotes telomeres are shorter than metacyclic and procyclic promastigotes and that in parasites with continuous in vitro passages, telomere length increases over time. These observed differences in telomere length among parasite’s life stages were not due to lack/inhibition of telomerase since enzyme activity was detected in all parasite life stages, although the catalysis was temperature-dependent. These data led us to test if, similar to other eukaryotes, parasite telomere length maintenance could be regulated by Hsp83, the ortholog of Hsp90 in trypanosomatids, and Leishmania (LHsp90). Parasites were then treated with the Hsp90 inhibitor 17AAG. The results showed that 17AAG disturbed parasite growth, induced accumulation into G2/M phases, and telomere shortening in a time-dependent manner. It has also inhibited procyclic promastigote’s telomerase activity. Besides, LHsp90 interacts with the telomerase TERT component as shown by immunoprecipitation, strongly suggesting a new role for LHsp90 as a parasite telomerase component involved in controlling telomere length maintenance and parasite life span.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Department of Chemical and Biological Sciences Institute of Biosciences São Paulo State University (UNESP)Faculdade Brazileira MultivixHemocentro da Faculdade de Medicina de Ribeirão Preto Universidade of São PauloSão Carlos Institute of Chemistry University of São PauloDepartment of Chemical and Biological Sciences Institute of Biosciences São Paulo State University (UNESP)Universidade Estadual Paulista (UNESP)Faculdade Brazileira MultivixUniversidade of São PauloUniversidade de São Paulo (USP)de Oliveira, Beatriz C. D. [UNESP]Shiburah, Mark E. [UNESP]Paiva, Stepany C. [UNESP]Vieira, Marina R. [UNESP]Morea, Edna Gicela O. [UNESP]da Silva, Marcelo Santos [UNESP]Alves, Cristiane de Santis [UNESP]Segatto, MarcelaGutierrez-Rodrigues, FernandaBorges, Júlio C.Calado, Rodrigo T.Cano, Maria Isabel N. [UNESP]2022-04-28T19:47:08Z2022-04-28T19:47:08Z2021-10-28info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://dx.doi.org/10.3389/fcell.2021.713415Frontiers in Cell and Developmental Biology, v. 9.2296-634Xhttp://hdl.handle.net/11449/22284910.3389/fcell.2021.7134152-s2.0-85118978629Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengFrontiers in Cell and Developmental Biologyinfo:eu-repo/semantics/openAccess2022-04-28T19:47:09Zoai:repositorio.unesp.br:11449/222849Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462022-04-28T19:47:09Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false
dc.title.none.fl_str_mv Possible Involvement of Hsp90 in the Regulation of Telomere Length and Telomerase Activity During the Leishmania amazonensis Developmental Cycle and Population Proliferation
title Possible Involvement of Hsp90 in the Regulation of Telomere Length and Telomerase Activity During the Leishmania amazonensis Developmental Cycle and Population Proliferation
spellingShingle Possible Involvement of Hsp90 in the Regulation of Telomere Length and Telomerase Activity During the Leishmania amazonensis Developmental Cycle and Population Proliferation
de Oliveira, Beatriz C. D. [UNESP]
continuous in vitro passages
Leishmania life forms
LHsp90
telomerase ribonucleoprotein complex
telomeres maintenance
title_short Possible Involvement of Hsp90 in the Regulation of Telomere Length and Telomerase Activity During the Leishmania amazonensis Developmental Cycle and Population Proliferation
title_full Possible Involvement of Hsp90 in the Regulation of Telomere Length and Telomerase Activity During the Leishmania amazonensis Developmental Cycle and Population Proliferation
title_fullStr Possible Involvement of Hsp90 in the Regulation of Telomere Length and Telomerase Activity During the Leishmania amazonensis Developmental Cycle and Population Proliferation
title_full_unstemmed Possible Involvement of Hsp90 in the Regulation of Telomere Length and Telomerase Activity During the Leishmania amazonensis Developmental Cycle and Population Proliferation
title_sort Possible Involvement of Hsp90 in the Regulation of Telomere Length and Telomerase Activity During the Leishmania amazonensis Developmental Cycle and Population Proliferation
author de Oliveira, Beatriz C. D. [UNESP]
author_facet de Oliveira, Beatriz C. D. [UNESP]
Shiburah, Mark E. [UNESP]
Paiva, Stepany C. [UNESP]
Vieira, Marina R. [UNESP]
Morea, Edna Gicela O. [UNESP]
da Silva, Marcelo Santos [UNESP]
Alves, Cristiane de Santis [UNESP]
Segatto, Marcela
Gutierrez-Rodrigues, Fernanda
Borges, Júlio C.
Calado, Rodrigo T.
Cano, Maria Isabel N. [UNESP]
author_role author
author2 Shiburah, Mark E. [UNESP]
Paiva, Stepany C. [UNESP]
Vieira, Marina R. [UNESP]
Morea, Edna Gicela O. [UNESP]
da Silva, Marcelo Santos [UNESP]
Alves, Cristiane de Santis [UNESP]
Segatto, Marcela
Gutierrez-Rodrigues, Fernanda
Borges, Júlio C.
Calado, Rodrigo T.
Cano, Maria Isabel N. [UNESP]
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universidade Estadual Paulista (UNESP)
Faculdade Brazileira Multivix
Universidade of São Paulo
Universidade de São Paulo (USP)
dc.contributor.author.fl_str_mv de Oliveira, Beatriz C. D. [UNESP]
Shiburah, Mark E. [UNESP]
Paiva, Stepany C. [UNESP]
Vieira, Marina R. [UNESP]
Morea, Edna Gicela O. [UNESP]
da Silva, Marcelo Santos [UNESP]
Alves, Cristiane de Santis [UNESP]
Segatto, Marcela
Gutierrez-Rodrigues, Fernanda
Borges, Júlio C.
Calado, Rodrigo T.
Cano, Maria Isabel N. [UNESP]
dc.subject.por.fl_str_mv continuous in vitro passages
Leishmania life forms
LHsp90
telomerase ribonucleoprotein complex
telomeres maintenance
topic continuous in vitro passages
Leishmania life forms
LHsp90
telomerase ribonucleoprotein complex
telomeres maintenance
description The Leishmania developmental cycle comprises three main life forms in two hosts, indicating that the parasite is continually challenged due to drastic environmental changes. The disruption of this cycle is critical for discovering new therapies to eradicate leishmaniasis, a neglected disease that affects millions worldwide. Telomeres, the physical ends of chromosomes, maintain genome stability and cell proliferation and are potential antiparasitic drug targets. Therefore, understanding how telomere length is regulated during parasite development is vital. Here, we show that telomeres form clusters spread in the nucleoplasm of the three parasite life forms. We also observed that amastigotes telomeres are shorter than metacyclic and procyclic promastigotes and that in parasites with continuous in vitro passages, telomere length increases over time. These observed differences in telomere length among parasite’s life stages were not due to lack/inhibition of telomerase since enzyme activity was detected in all parasite life stages, although the catalysis was temperature-dependent. These data led us to test if, similar to other eukaryotes, parasite telomere length maintenance could be regulated by Hsp83, the ortholog of Hsp90 in trypanosomatids, and Leishmania (LHsp90). Parasites were then treated with the Hsp90 inhibitor 17AAG. The results showed that 17AAG disturbed parasite growth, induced accumulation into G2/M phases, and telomere shortening in a time-dependent manner. It has also inhibited procyclic promastigote’s telomerase activity. Besides, LHsp90 interacts with the telomerase TERT component as shown by immunoprecipitation, strongly suggesting a new role for LHsp90 as a parasite telomerase component involved in controlling telomere length maintenance and parasite life span.
publishDate 2021
dc.date.none.fl_str_mv 2021-10-28
2022-04-28T19:47:08Z
2022-04-28T19:47:08Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://dx.doi.org/10.3389/fcell.2021.713415
Frontiers in Cell and Developmental Biology, v. 9.
2296-634X
http://hdl.handle.net/11449/222849
10.3389/fcell.2021.713415
2-s2.0-85118978629
url http://dx.doi.org/10.3389/fcell.2021.713415
http://hdl.handle.net/11449/222849
identifier_str_mv Frontiers in Cell and Developmental Biology, v. 9.
2296-634X
10.3389/fcell.2021.713415
2-s2.0-85118978629
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Frontiers in Cell and Developmental Biology
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.source.none.fl_str_mv Scopus
reponame:Repositório Institucional da UNESP
instname:Universidade Estadual Paulista (UNESP)
instacron:UNESP
instname_str Universidade Estadual Paulista (UNESP)
instacron_str UNESP
institution UNESP
reponame_str Repositório Institucional da UNESP
collection Repositório Institucional da UNESP
repository.name.fl_str_mv Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)
repository.mail.fl_str_mv
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