Hyperglycemic memory effects on epigenetic marks in HepG2 cells

• Grant number: 12/20444-8
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: April 01, 2013
• End date: April 30, 2014
• Field of knowledge: Biological Sciences - Morphology - Cytology and Cell Biology
• Principal Investigator: Maria Luiza Silveira Mello
• Grantee: Flávia Gerelli Ghiraldini
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 10/50015-6 - Chromatin structure and organization with aging and diabetes compared to induced changes in epigenetic markers, AP.TEM

Abstract

Diabetes mellitus type 1 (DM) is an auto-immune disease in which T-lymphocytes promote the destruction of ²-cells from the Langerhans islets, thus inducing failure in insulin production and increasing glucose levels in the bloodstream. If not intensively controlled, hyperglycemia can lead to secondary complications such as retinopathies, nephropathies and vascular diseases. Recent reports indicated that hyperglycemia can promote persistent changes in gene expression and epigenetic markers in endothelial cell cultures even after cell transfer to a normoglycemic medium. Histone deacetilases are known to alter chromatin conformation and structure; their main targets are histones H3 and H4 acetylated lysine residues. Sirtuins, specifically, play a role in changing epigenetic markers in diabetes mellitus and there is evidence that these proteins could be involved in the hyperglycemic memory. In this work, we aim to detect in greater depth whether Sirt1 and strategic epigenetic markers, such as histone H3 lysine 9 acetylation and di-methylation, are related to the hyperglycemic memory through changes in chromatin conformation and gene expression regulation.