Effect of progesterone on the expression of proteins involved in oxidative stress in pancreatic beta cells: new perspectives for the study of gestational diabetes

• Grant number: 17/25126-8
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): February 01, 2018
• Effective date (End): December 31, 2018
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Viviane Abreu Nunes Cerqueira Dantas
• Grantee: Gustavo Roncoli Reigado
• Host Institution: Escola de Artes, Ciências e Humanidades (EACH). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Gestational diabetes (GD) is a condition defined as carbohydrate intolerance and hyperglycemia,beginning in the second trimester of pregnancy. Studies developed by our group showed that progesterone (PG), a hormone whose concentration increases considerably during pregnancy, is capable of causing death of pancreatic beta-cells, which could contribute to the development of the DG and reflect on maternal inability to respond to enhanced demand for insulin. Although the pathways involved in the mechanism of cell death induced by PG have not yet been fully elucidated, our group observed that cell death induced by PG was attenuated or abolished in the preincubation of the cells with alpha-tocopherol, an antioxidant vitamin. We have also shown that progesterone is capable of modulating the expression of genes involved in oxidative stress and antioxidant defense pathways, such as those encoding heat shock protein a1a (Hspa1a), glutathione peroxidase 6 (Gpx6), dual oxidase 1 (Duox1), heme oxygenase 1 (Hmox1), and stearoyl-CoA desaturase-1 (Scd1), which together with peroxiredoxin 4 (Prdx4) perform functions related to pancreatic cells and/or DG. In this context, this project aims to study in detail the effect of PG on the expression of the proteins encoded by the genes Hspa1a, Gpx6, Duox1, Hmox, Scd1 and Pdrx4 by ELISA and/or western blotting in RINm5f pancreatic beta cells. This project should contribute to a better understanding of the pathogenesis of the DG, opening perspectives for the development of strategies for the prevention and treatment of this disease. (AU)