Possible Involvement of Hsp90 in the Regulation of Telomere Length and Telomerase Activity During the Leishmania amazonensis Developmental Cycle and Population Proliferation
Autor(a) principal: | |
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Data de Publicação: | 2021 |
Outros Autores: | , , , , , , , , , , |
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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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 |
|
_version_ |
1799965284113580032 |