Chrysin reduces the activity and protein level of mature forms of sterol regulatory element-binding proteins.

ABSTRACT

Sterol regulatory element-binding proteins (SREBPs) are transcription factors that regulate the expression of genes involved in fatty acid and cholesterol biosynthetic pathways. The present study showed that the flavonoid chrysin impairs the fatty acid synthase promoter. Chrysin reduces the expression of SREBP target genes, such as fatty acid synthase, in human hepatoma Huh-7 cells and impairs de novo synthesis of fatty acids and cholesterol. Moreover, it reduces the endogenous mature, transcriptionally active forms of SREBPs, which are generated by the proteolytic processing of precursor forms. In addition, chrysin reduces the enforced expressing mature forms of SREBPs and their transcriptional activity. The ubiquitin-proteasome system is not involved in the chrysin-mediated reduction of SREBPs mature forms. These results suggest that chrysin suppresses SREBP activity, at least partially, via the degradation of SREBPs mature forms. Abbreviations ACC1 acetyl-CoA carboxylase 1; DMEM Dulbecco's modified Eagle's medium; FAS fatty acid synthase; GAPDH glyceraldehyde-3-phosphate dehydrogenase; 25-HC 25-hydroxycholesterol; HMGCS HMG-CoA synthase; LDH lactate dehydrogenase; LPDS lipoprotein-deficient serum; PI3K phosphatidylinositol 3-kinase; SCD1 stearoyl-CoA desaturase; SREBPs sterol regulatory element-binding proteins.