Unveiling the role of HSP25/27 in Prolactin-induced cytoprotection in pancreatic beta cells

• Grant number: 13/07029-4
• Support Opportunities: Regular Research Grants
• Start date: February 01, 2014
• End date: July 31, 2016
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Leticia Labriola
• Grantee: Leticia Labriola
• Host Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated researchers: Fernando Rodrigues de Moraes Abdulkader

Abstract

One of the goals in the treatment for diabetes is to enhance pancreatic beta-cell function, proliferation and survival. Beta-cell apoptosis occurs in diabetes where genes of bcl-2 family members are known either promote or to inhibit it. Recent results from our group showed that recombinant human prolactin (rhPRL) inhibits beta-cell apoptosis. Using bidimensional gel electrophoresis, we reported up-regulation of HSP25/27 upon rhPRL treatment. Even when members of the family of heat shock proteins are known to mitigate apoptosis after numerous challenges, the cytoprotective effects of HSP25/27 on beta cells have not been directly studied. Until today, there is only one report describing that mice presenting constitutive expression of HSP27 are less sensitive to pharmacological induced type 1diabetes mellitus (DM1). Therefore, we set out to study on a first step, whether HSP25/27 could be a mediator of PRL-induced inhibition of beta-cell death and if so, to unveil the molecular mechanisms supporting this action on murine and human beta-cell models. For this purpose, we aim at generating beta cell lines over expressing specific shRNA directed to knock-down the expression of HSP25/27 and then using these models, to evaluate the sensitivity of the cells upon inflammatory cytokines-induced cell death as a model of DM1. Moreover following the data described in the literature for other cellular models, we intend to search for possible interactions of HSP25/27 with protein mediators of the intrinsic pathway leading to apoptosis. Collectively, our results could lead to the development of novel methods of islet cytoprotection based on this approach. (AU)

Scientific publications

(5)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

LAMBELET, MARTINE; TERRA, LETICIA F.; FUKAYA, MAKIKO; MEYEROVICH, KIRA; LABRIOLA, LETICIA; CARDOZO, ALESSANDRA K.; ALLAGNAT, FLORENT. Dysfunctional autophagy following exposure to pro-inflammatory cytokines contributes to pancreatic beta-cell apoptosis. CELL DEATH & DISEASE, v. 9, JAN 24 2018. (13/07029-4)

L. ANDREONE; A.F. DOS SANTOS; R.A.M. WAILEMANN; L.F. TERRA; V.M. GOMES; J. MACEDO DA SILVA; L. ROSA-FERNANDES; M.C. SOGAYAR; G. PALMISANO; L. LABRIOLA; et al. Cotransplantation of marginal mass allogeneic islets with 3D culture-derived adult human skin cells improves glycemia in diabetic mice. Brazilian Journal of Medical and Biological Research, v. 56, 2023-09-22. (12/50680-5, 16/05311-2, 13/07937-8, 13/07029-4, 12/16785-4)

DOS SANTOS, ANCELY F.; TERRA, LETICIA F.; WAILEMANN, ROSANGELA A. M.; OLIVEIRA, TALITA C.; GOMES, VINICIUS DE MORAIS; MINEIRO, MARCELA FRANCO; MEOTTI, FLAVIA CARLA; BRUNI-CARDOSO, ALEXANDRE; BAPTISTA, MAURICIO S.; LABRIOLA, LETICIA. Methylene blue photodynamic therapy induces selective and massive cell death in human breast cancer cells. BMC CANCER, v. 17, MAR 15 2017. (13/07029-4, 12/16785-4, 13/07937-8, 12/50680-5)

WAILEMANN, ROSANGELA A. M.; TERRA, LETICIA F.; OLIVEIRA, TALITA C.; DOS SANTOS, ANCELY F.; GOMES, VINICIUS M.; LABRIOLA, LETICIA. Heat shock protein B1 is required for the prolactin-induced cytoprotective effects on pancreatic islets. Molecular and Cellular Endocrinology, v. 477, p. 39-47, DEC 5 2018. (14/17974-0, 14/02745-6, 13/13914-0, 13/07029-4, 16/04676-7, 17/03618-6)

TERRA, LETICIA F.; WAILEMANN, ROSANGELA A. M.; DOS SANTOS, ANCELY F.; GOMES, VINICIUS M.; SILVA, RAILMARA P.; LAPORTE, ANNA; MEOTTI, FLAVIA C.; TERRA, WALTER R.; PALMISANO, GIUSEPPE; LORTZ, STEPHAN; et al. Heat shock protein B1 is a key mediator of prolactin-induced beta-cell cytoprotection against oxidative stress. Free Radical Biology and Medicine, v. 134, p. 394-405, APR 2019. (16/02881-2, 14/17974-0, 13/07029-4, 17/03618-6, 14/02745-6, 13/13914-0)