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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Heat shock protein B1 is a key mediator of prolactin-induced beta-cell cytoprotection against oxidative stress

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Author(s):
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Terra, Leticia F. [1, 2] ; Wailemann, Rosangela A. M. [1] ; dos Santos, Ancely F. [1] ; Gomes, Vinicius M. [1] ; Silva, Railmara P. [1] ; Laporte, Anna [2] ; Meotti, Flavia C. [1] ; Terra, Walter R. [1] ; Palmisano, Giuseppe [3] ; Lortz, Stephan [2] ; Labriola, Leticia [1]
Total Authors: 11
Affiliation:
[1] Univ Sao Paulo, Inst Quim, Dept Bioquim, Ave Prof Lineu Prestes 748, BR-05508000 Sao Paulo - Brazil
[2] Hannover Med Sch MHH, Inst Clin Biochem, Carl Neuberg Str 1, D-30625 Hannover - Germany
[3] Univ Sao Paulo, Dept Parasitol, Inst Ciencias Biomed, Edificio 2, Ave Prof Lineu Prestes 1374, R-05508000 Sao Paulo - Brazil
Total Affiliations: 3
Document type: Journal article
Source: Free Radical Biology and Medicine; v. 134, p. 394-405, APR 2019.
Web of Science Citations: 0
Abstract

Maintaining islet cell viability in vitro, although challenging, appears to be a strategy for improving the outcome of pancreatic islet transplantation. We have shown that prolactin (PRL) leads to beta-cell cytoprotection against apoptosis, an effect mediated by heat shock protein B1 (HSPB1). Since the role of HSPB1 in beta-cells is still unclear and the hormone concentration used is not compatible with clinical applications because of all the side effects displayed by the hormone in other tissues, we explored the molecular mechanisms by which HSPB1 mediates beta-cell cytoprotection. Lysates from PRL- and/or cytokine-treated MIN6 beta-cells were subjected to HSPB1 immunoprecipitation followed by identification through mass spectrometry. PRL-treated cells presented an enrichment of several proteins co-precipitating with HSPB1. Of note were oxidative stress resistance-, protein degradation-and carbohydrate metabolism-related proteins. Wild type, HSPB1 silenced or overexpressing MIN6 cells were exposed to menadione and hydrogen peroxide and analysed for several oxidative stress parameters. HSPB1 knockdown rendered cells more sensitive to oxidative stress and led to a reduced antioxidant capacity, while prolactin induced an HSPB1-mediated cytoprotection against oxidative stress. HSPB1 overexpression, however, led to opposite effects. PRL treatment, HSPB1 silencing or overexpression did not change the expression nor activities of antioxidant enzymes, it also did not lead to a modulation of total glutathione levels nor G6PD expression. However, HSPB1 levels are related to a modulation of GSH/GSSG ratio, G6PD activity and NADPH/NADP(+) ratio. We have shown that HSPB1 is important for pro-survival effects against oxidative stress-induced beta-cell death. These results are in accordance with PRL-induced enrichment of HSPB1-interacting proteins related to protection against oxidative stress. Finally, our results outline the need of further studies investigating the importance of HSPB1 for beta-cell viability, since this could lead to the mitigation of beta-cell death through the upregulation of an endogenous protective pathway. (AU)

FAPESP's process: 16/02881-2 - PRL and HSPB1 effects in the autophagy and oxidative stress of beta-cells
Grantee:Letícia Ferreira Terra
Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
FAPESP's process: 14/17974-0 - Unveiling the role of HSPB1 in prolactin-induced cytoprotection in pancreatic beta cells
Grantee:Vinícius de Morais Gomes
Support Opportunities: Scholarships in Brazil - Master
FAPESP's process: 13/07029-4 - Unveiling the role of HSP25/27 in Prolactin-induced cytoprotection in pancreatic beta cells
Grantee:Leticia Labriola
Support Opportunities: Regular Research Grants
FAPESP's process: 17/03618-6 - Unveiling HSPB1's role in prolactin-induced modulation of the unfolded protein response in type 1 Diabetes models
Grantee:Leticia Labriola
Support Opportunities: Regular Research Grants
FAPESP's process: 14/02745-6 - Unveiling the molecular mechanisms involved in Prolactin-induced cytoprotection in Pancreatic Beta Cells.
Grantee:Rosangela Aparecida Wailemann Mansano
Support Opportunities: Scholarships in Brazil - Doctorate
FAPESP's process: 13/13914-0 - Autophagy in beta-cells and the cytoprotective roles of prolactin
Grantee:Letícia Ferreira Terra
Support Opportunities: Scholarships in Brazil - Post-Doctoral