Expression of human HSP27 in yeast extends replicative lifespan and uncovers a hormetic response

Author(s)

Camandona, Vittoria de Lima ^[1] ; Rios-Anjos, Rafaela Maria ^[1] ; Alegria, Thiago Geronimo Pires ^[2] ; Pereira, Fabio ^[1] ; Bicev, Renata Naporano ^[3] ; da Cunha, Fernanda Marques ^[3] ; Digiampietri, Luciano Antonio ^[1] ; de Barros, Mario Henrique ^[4] ; Netto, Luis Eduardo Soares ^[2] ; Ferreira-Junior, Jose Ribamar ^[1]

Affiliation

^[1] Univ Sao Paulo, Escola Artes Ciencias & Humanidades, Sao Paulo - Brazil

^[2] Univ Sao Paulo, Inst Biociencias, Dept Genet & Biol Evolut, Sao Paulo - Brazil

^[3] Univ Fed Sao Paulo, Dept Bioquim, Sao Paulo - Brazil

^[4] Univ Sao Paulo, Inst Ciencias Biomed, Dept Microbiol, Sao Paulo - Brazil

• Document type: Journal article
• Source: BIOGERONTOLOGY; v. 21, n. 5 MAR 2020.
• Web of Science Citations: 0

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 \& apos;s and Parkinson \& apos;s diseases. To better understand the 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 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. (AU)

• FAPESP's process: 17/09938-2 - Analysis of the effect of human HSP27 overexpression on the longevity of Saccharomyces cerevisiae
• Grantee: José Ribamar dos Santos Ferreira Júnior
• Support type: Regular Research Grants
• FAPESP's process: 13/07937-8 - Redoxome - Redox Processes in Biomedicine
• Grantee: Ohara Augusto
• Support type: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 16/11724-8 - Calorie Restriction effects on the proteasome of yeast Saccharomyces cerevisiae
• Grantee: Renata Naporano Bicev
• Support type: Scholarships in Brazil - Doctorate