ex-527 and Fatty-Liver

High mobility group box-1 (HMGB1), recognized as a representative of damage-associated molecular patterns, is released during cell injury/death, triggering the inflammatory response and ultimately resulting in tissue damage. Dozens of studies have shown that HMGB1 is involved in certain diseases, but the details on how injured hepatocytes release HMGB1 need to be elicited.. To reveal HMGB1 release mechanism in hepatocytes undergoing oxidative stress.. When hepatocytes were damaged, HMGB1 translocated from the nucleus to the cytoplasm because of its hyperacetylation and was passively released outside both in vivo and in vitro. After treatment with Sirt1-siRNA or Sirt1 inhibitor (EX527), the hyperacetylated HMGB1 in hepatocytes increased, and Sirt1 activity inhibited by H. The functional inhibition between Parp1 and Sirt1 leads to HMGB1 hyperacetylation, which leads to its translocation from the nucleus to the cytoplasm and finally outside the cell.

Topics: Acetylation; Animals; Carbazoles; Cell Line; Cell Nucleus; Cells, Cultured; Cytoplasm; Diet, High-Fat; Disease Models, Animal; Ethanol; Fatty Liver; Hepatocytes; HMGB1 Protein; Humans; Hydrogen Peroxide; Liver; Liver Function Tests; Male; Mice; Oxidative Stress; Poly (ADP-Ribose) Polymerase-1; Quinolinium Compounds; RNA, Small Interfering; Sirtuin 1