Identification of a novel target of sulforaphane: Sulforaphane binds to acyl-protein thioesterase 2 (APT2) and attenuates its palmitoylation.

Sulforaphane (SFaN) is a food-derived compound with several bioactive properties, including atherosclerosis, diabetes, and obesity treatment. However, the mechanisms by which SFaN exerts its various effects are still unclear. To elucidate the mechanisms of the various effects of SFaN, we explored novel SFaN-binding proteins using SFaN beads and identified acyl protein thioesterase 2 (APT2). We also found that SFaN binds to the APT2 via C56 residue and attenuates the palmitoylation of APT2, thereby reducing plasma membrane localization of APT2. This study reveals a novel bioactivity of SFaN as a regulator of APT2 protein palmitoylation.

Hydrophilic oxygen radical absorbance capacity values of low-molecular-weight phenolic compounds containing carbon, hydrogen, and oxygen.

The antioxidant capacity of an antioxidant reflects its ability to remove reactive oxygen species (ROS). In this study, the hydrophilic oxygen radical absorbance capacity (H-ORAC) method was used to quantitatively evaluate the antioxidant capacities of natural phenols and their derivatives against peroxyl radicals. This method was comprehensively applied to low-molecular-weight phenols to construct a database. Although no macroscopic correlation was observed for values related to the antioxidant capacity expression, we observed a difference in the trend of the H-ORAC values for each functional group. Thus, this database will serve as a new benchmark and tool for molecular design.

Sulforaphane suppresses the activity of sterol regulatory element-binding proteins (SREBPs) by promoting SREBP precursor degradation.

Sterol regulatory element-binding proteins (SREBPs) are transcription factors that regulate various genes involved in cholesterol and fatty acid synthesis. In this study, we describe that naturally occurring isothiocyanate sulforaphane (SFaN) impairs fatty acid synthase promoter activity and reduces SREBP target gene (e.g., fatty acid synthase and acetyl-CoA carboxylase 1) expression in human hepatoma Huh-7 cells. SFaN reduced SREBP proteins by promoting the degradation of the SREBP precursor. Amino acids 595-784 of SREBP-1a were essential for SFaN-mediated SREBP-1a degradation. We also found that such SREBP-1 degradation occurs independently of the SREBP cleavage-activating protein and the Keap1-Nrf2 pathway. This study identifies SFaN as an SREBP inhibitor and provides evidence that SFaN could have major potential as a pharmaceutical preparation against hepatic steatosis and obesity.