Effects of valproic acid and trichostatin A on chromatin organization and its regulation by epigenetic factors in HepG2 cells grown under hyperglycemic conditions

Abstract

Diabetes mellitus (DM) is a group of chronic diseases in which the relative or absolute lack of insulin leads to aberrations in the metabolism of their substrates, causing acute and late complications. DM is one of the most common non-transmissible global diseases. It is the fourth or fifth leading cause of death in developed countries and has significant effects on the public health budget of all societies. Therefore, even in the 21st century, the DM remains one of the most challenging health problems. A complex interaction among environmental, nutritional and genetic factors works in the diabetes pathogenesis, pointing to the role of epigenetic control. Histone deacetylases (HDACs) are known to be involved in several relevant biological pathways to the DM etiology and pathogenesis. In the last years, HDAC inhibition has emerged as a potential strategy to reverse epigenetic changes associated with several diseases and many different structural classes of HDAC inhibitors (HDACis) have been identified. A role of HDACi preventing inflammatory damage in the pancreatic beta cells, in addition to improving insulin resistance, has already been reported. Considering that the liver is an essential organ for glucose and lipid metabolism, it is an important environment for the study of the action of HDACis, as valproic acid (VPA) and trichostatin A (TSA), under DM conditions. Thus, the focus of study, which will be developed in a liver cell model (HepG2) under hyperglycemic conditions, concentrates on changes in chromatin structure associated with changes in epigenetics marks and on the epigenetic control of FoxO1 gene, a transcription factor responsible for glucose metabolism control. (AU)