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

Autor(es):Mostrar menos -

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]

Afiliação do(s) autor(es)

^[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

• Tipo de documento: Artigo Científico
• Fonte: Free Radical Biology and Medicine; v. 134, p. 394-405, APR 2019.
• Citações Web of Science: 0

Resumo

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)

• Processo FAPESP: 16/02881-2 - Efeitos da PRL e de HSPB1 na autofagia e estresse oxidativo de células-beta
• Beneficiário: Letícia Ferreira Terra
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Pós-Doutorado
• Processo FAPESP: 14/17974-0 - Estudo da função de HSPB1 na citoproteção induzida por prolactina em células beta pancreáticas
• Beneficiário: Vinícius de Morais Gomes
• Modalidade de apoio: Bolsas no Brasil - Mestrado
• Processo FAPESP: 13/07029-4 - Estudo do papel da proteína HSP27/25 na citoproteção de células beta pancreáticas induzida por prolactina
• Beneficiário: Leticia Labriola
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 17/03618-6 - Estudo da função de HSPB1 na modulação da resposta a proteínas mal dobradas em modelos de Diabetes tipo 1
• Beneficiário: Leticia Labriola
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 14/02745-6 - Mecanismos Moleculares Mediadores da Citoproteção de Células Beta Pancreáticas Induzida por Prolactina
• Beneficiário: Rosangela Aparecida Wailemann Mansano
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 13/13914-0 - Papel citoprotetor da prolactina na autofagia de células-beta
• Beneficiário: Letícia Ferreira Terra
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado