Possible Involvement of Hsp90 in the Regulation of Telomere Length and Telomerase Activity During the Leishmania amazonensis Developmental Cycle and Population Proliferation
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 af...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-10-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2021.713415/full |
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| author | Beatriz C. D. de Oliveira Mark E. Shiburah Stephany C. Paiva Marina R. Vieira Edna Gicela O. Morea Marcelo Santos da Silva Cristiane de Santis Alves Marcela Segatto Fernanda Gutierrez-Rodrigues Júlio C. Borges Rodrigo T. Calado Maria Isabel N. Cano |
| author_facet | Beatriz C. D. de Oliveira Mark E. Shiburah Stephany C. Paiva Marina R. Vieira Edna Gicela O. Morea Marcelo Santos da Silva Cristiane de Santis Alves Marcela Segatto Fernanda Gutierrez-Rodrigues Júlio C. Borges Rodrigo T. Calado Maria Isabel N. Cano |
| author_sort | Beatriz C. D. de Oliveira |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-04-14T04:43:43Z |
| format | Article |
| id | doaj.art-8a34f62857614ae1937012fee2af69cd |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-04-14T04:43:43Z |
| publishDate | 2021-10-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-8a34f62857614ae1937012fee2af69cd2022-12-22T02:11:32ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2021-10-01910.3389/fcell.2021.713415713415Possible Involvement of Hsp90 in the Regulation of Telomere Length and Telomerase Activity During the Leishmania amazonensis Developmental Cycle and Population ProliferationBeatriz C. D. de Oliveira0Mark E. Shiburah1Stephany C. Paiva2Marina R. Vieira3Edna Gicela O. Morea4Marcelo Santos da Silva5Cristiane de Santis Alves6Marcela Segatto7Fernanda Gutierrez-Rodrigues8Júlio C. Borges9Rodrigo T. Calado10Maria Isabel N. Cano11Department of Chemical and Biological Sciences, Institute of Biosciences, São Paulo State University (UNESP), São Paulo, BrazilDepartment of Chemical and Biological Sciences, Institute of Biosciences, São Paulo State University (UNESP), São Paulo, BrazilDepartment of Chemical and Biological Sciences, Institute of Biosciences, São Paulo State University (UNESP), São Paulo, BrazilDepartment of Chemical and Biological Sciences, Institute of Biosciences, São Paulo State University (UNESP), São Paulo, BrazilDepartment of Chemical and Biological Sciences, Institute of Biosciences, São Paulo State University (UNESP), São Paulo, BrazilDepartment of Chemical and Biological Sciences, Institute of Biosciences, São Paulo State University (UNESP), São Paulo, BrazilDepartment of Chemical and Biological Sciences, Institute of Biosciences, São Paulo State University (UNESP), São Paulo, BrazilFaculdade Brazileira Multivix, Vitória, BrazilHemocentro da Faculdade de Medicina de Ribeirão Preto, Universidade of São Paulo, São Paulo, BrazilSão Carlos Institute of Chemistry, University of São Paulo, São Paulo, BrazilHemocentro da Faculdade de Medicina de Ribeirão Preto, Universidade of São Paulo, São Paulo, BrazilDepartment of Chemical and Biological Sciences, Institute of Biosciences, São Paulo State University (UNESP), São Paulo, BrazilThe 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.https://www.frontiersin.org/articles/10.3389/fcell.2021.713415/fullLeishmania life formscontinuous in vitro passagestelomeres maintenancetelomerase ribonucleoprotein complexLHsp90 |
| spellingShingle | Beatriz C. D. de Oliveira Mark E. Shiburah Stephany C. Paiva Marina R. Vieira Edna Gicela O. Morea Marcelo Santos da Silva Cristiane de Santis Alves Marcela Segatto Fernanda Gutierrez-Rodrigues Júlio C. Borges Rodrigo T. Calado Maria Isabel N. Cano Possible Involvement of Hsp90 in the Regulation of Telomere Length and Telomerase Activity During the Leishmania amazonensis Developmental Cycle and Population Proliferation Frontiers in Cell and Developmental Biology Leishmania life forms continuous in vitro passages telomeres maintenance telomerase ribonucleoprotein complex LHsp90 |
| title | 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_short | 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 |
| topic | Leishmania life forms continuous in vitro passages telomeres maintenance telomerase ribonucleoprotein complex LHsp90 |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2021.713415/full |
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