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Trichostatin A induces Trypanosoma cruzi histone and tubulin acetylation: effects on cell division and microtubule cytoskeleton remodelling

Published online by Cambridge University Press:  13 November 2018

Jean de Oliveira Santos ,
Aline Araujo Zuma Open the ORCID record for Aline Araujo Zuma [Opens in a new window] ,
Francisca Nathalia de Luna Vitorino ,
Julia Pinheiro Chagas da Cunha ,
Wanderley de Souza  and
Maria Cristina M. Motta
Jean de Oliveira Santos
Affiliation:
Laboratório de Ultraestrutura Celular Hertha Meyer, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro-UFRJ, 21491-590, Rio de Janeiro, RJ, Brazil Instituto Nacional de Ciência e Tecnologia e Núcleo de Biologia Estrutural e Bioimagens – CENABIO, UFRJ, RJ, Brazil
Aline Araujo Zuma
Affiliation:
Laboratório de Ultraestrutura Celular Hertha Meyer, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro-UFRJ, 21491-590, Rio de Janeiro, RJ, Brazil Instituto Nacional de Ciência e Tecnologia e Núcleo de Biologia Estrutural e Bioimagens – CENABIO, UFRJ, RJ, Brazil
Francisca Nathalia de Luna Vitorino
Affiliation:
Laboratório Especial de Ciclo Celular, Center of Toxins, Immune Response and Cell Signaling – CeTICS, Instituto Butantan, São Paulo, 05503-900, SP, Brazil
Julia Pinheiro Chagas da Cunha
Affiliation:
Laboratório Especial de Ciclo Celular, Center of Toxins, Immune Response and Cell Signaling – CeTICS, Instituto Butantan, São Paulo, 05503-900, SP, Brazil
Wanderley de Souza
Affiliation:
Laboratório de Ultraestrutura Celular Hertha Meyer, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro-UFRJ, 21491-590, Rio de Janeiro, RJ, Brazil Instituto Nacional de Ciência e Tecnologia e Núcleo de Biologia Estrutural e Bioimagens – CENABIO, UFRJ, RJ, Brazil
Maria Cristina M. Motta*
Affiliation:
Laboratório de Ultraestrutura Celular Hertha Meyer, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro-UFRJ, 21491-590, Rio de Janeiro, RJ, Brazil Instituto Nacional de Ciência e Tecnologia e Núcleo de Biologia Estrutural e Bioimagens – CENABIO, UFRJ, RJ, Brazil
*
Author for correspondence: Maria Cristina M. Motta, E-mail: [email protected]
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Abstract

Trypanosoma cruzi, the causative agent of Chagas disease, is a public health concern in Latin America. Epigenetic events, such as histone acetylation, affect DNA topology, replication and gene expression. Histone deacetylases (HDACs) are involved in chromatin compaction and post-translational modifications of cytoplasmic proteins, such as tubulin. HDAC inhibitors, like trichostatin A (TSA), inhibit tumour cell proliferation and promotes ultrastructural modifications. In the present study, TSA effects on cell proliferation, viability, cell cycle and ultrastructure were evaluated, as well as on histone acetylation and tubulin expression of the T. cruzi epimastigote form. Protozoa proliferation and viability were reduced after treatment with TSA. Quantitative proteomic analyses revealed an increase in histone acetylation after 72 h of TSA treatment. Surprisingly, results obtained by different microscopy methodologies indicate that TSA does not affect chromatin compaction, but alters microtubule cytoskeleton dynamics and impair kDNA segregation, generating polynucleated cells with atypical morphology. Confocal fluorescence microscopy and flow cytometry assays indicated that treated cell microtubules were more intensely acetylated. Increases in tubulin acetylation may be directly related to the higher number of parasites in the G2/M phase after TSA treatment. Taken together, these results suggest that deacetylase inhibitors represent excellent tools for understanding trypanosomatid cell biology.

Keywords

Acetylationhistonehistone deacetylases inhibitor (HDACi)microtubule cytoskeletontrichostatin A (TSA)Trypanosoma cruzitubulin
Type
Research Article
Information
Parasitology , Volume 146 , Issue 4 , April 2019 , pp. 543 - 552
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Copyright
Copyright © Cambridge University Press 2018 

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Footnotes

*

Both authors contributed equally to this scientific article.

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