Expression of human HSP27 in yeast extends replicative lifespan and uncovers a hormetic response
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RESEARCH ARTICLE
Expression of human HSP27 in yeast extends replicative lifespan and uncovers a hormetic response Vittoria de Lima Camandona . Rafaela Maria Rios-Anjos . Thiago Geronimo Pires Alegria . Fa´bio Pereira . Renata Naporano Bicev . Fernanda Marques da Cunha . Luciano Antonio Digiampietri . Ma´rio Henrique de Barros . Luis Eduardo Soares Netto . Jose Ribamar Ferreira-Junior
Received: 17 December 2019 / Accepted: 13 March 2020 Springer Nature B.V. 2020
Abstract Human HSP27 is a small heat shock protein that modulates the ability of cells to respond to heat shock and oxidative stress, and also functions as a chaperone independent of ATP, participating in the proteasomal degradation of proteins. The expression of HSP27 is associated with survival in mammalian cells. In cancer cells, it confers resistance to chemotherapy; in neurons, HSP27 has a positive effect on neuronal viability in models of Alzheimer&s and Parkinson&s diseases. To better understand the Electronic supplementary material The online version of this article (https://doi.org/10.1007/s10522-020-09869-9) contains supplementary material, which is available to authorized users. V. L. Camandona R. M. Rios-Anjos F. Pereira L. A. Digiampietri J. R. Ferreira-Junior (&) Escola de Artes, Cieˆncias e Humanidades, Universidade de Sa˜o Paulo, Sa˜o Paulo, Brazil e-mail: [email protected] R. M. Rios-Anjos e-mail: [email protected] F. Pereira e-mail: [email protected] L. A. Digiampietri e-mail: [email protected] T. G. P. Alegria L. E. S. Netto Departamento de Gene´tica e Biologia Evolutiva, Instituto de Biocieˆncias, Universidade de Sa˜o Paulo, Sa˜o Paulo, Brazil e-mail: [email protected]
mechanism by which HSP27 expression contributes to cell survival, we expressed human HSP27 in the budding yeast Saccharomyces cerevisiae under control of different mutant TEF promoters, that conferred nine levels of graded basal expression, and showed that replicative lifespan and proteasomal activity increase as well as the resistance to oxidative and thermal stresses. The profile of these phenotypes display a dose–response effect characteristic of hormesis, an adaptive phenomenon that is observed when cells are exposed to increasing amounts of stress or toxic substances. The hormetic response correlates with changes in expression levels of HSP27 and also with its oligomeric states when correlated to survival L. E. S. Netto e-mail: [email protected] R. N. Bicev F. M. da Cunha Departamento de Bioquı´mica, Universidade Federal de Sa˜o Paulo, Sa˜o Paulo, Brazil e-mail: [email protected] F. M. da Cunha e-mail: [email protected] M. H. de Barros Departamento de Microbiologia – Instituto de Cieˆncias Biome´dicas, Universidade de Sa˜o Paulo, Sa˜o Paulo, Brazil e-mail: [email protected]
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Biogerontology
assays. Our results indicate that fine tuning of HSP27 concentration could be used as a strategy for cancer therapy, and also for improving neuronal survival in neurodegenerative diseases. K
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