title: Allyl isothiocyanate suppresses the proteolytic activation of sterol regulatory element-binding proteins and de novo fatty acid and cholesterol synthesis.
abstract: Sterol regulatory element-binding proteins (SREBPs) are a family of transcription factors that regulate lipid homeostasis by controlling the expression of genes involved in fatty acid and cholesterol synthesis. In this study, we used a stable cell line that expresses a luciferase reporter gene driven by an SRE-containing fatty acid synthase promoter to identify allyl isothiocyanate (AITC), one of the major isothiocyanates in cruciferous vegetables, as a novel SREBP inactivator. We found that AITC downregulated the proteolytic processing of SREBPs and the expression of their target genes in human hepatoma Huh-7 cells. Furthermore, AITC reduced the de novo synthesis of both fatty acids and cholesterol. Our results indicate a novel physiological function of AITC in lipid metabolism regulation.
authors.affiliation: a Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences , The University of Tokyo , Japan.
authors.forename: Shingo
authors.initials: S
authors.lastname: Miyata
authors.affiliation: a Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences , The University of Tokyo , Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Inoue
authors.affiliation: a Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences , The University of Tokyo , Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Shimizu
authors.affiliation: a Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences , The University of Tokyo , Japan.
authors.forename: Ryuichiro
authors.initials: R
authors.lastname: Sato
mesh_terms: D000103:Acetyl-CoA Carboxylase / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002784:Cholesterol / Q000378:metabolism*; D005227:Fatty Acids / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D022781:Hepatocytes; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000235:genetics / Q000378:metabolism; D006904:Hydroxymethylglutaryl-CoA Synthase / Q000235:genetics / Q000378:metabolism; D017879:Isothiocyanates / Q000494:pharmacology*; D050356:Lipid Metabolism / Q000187:drug effects / Q000235:genetics; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic; D059748:Proteolysis / Q000187:drug effects*; D015398:Signal Transduction; D013230:Stearoyl-CoA Desaturase / Q000235:genetics / Q000378:metabolism; D051780:Sterol Regulatory Element Binding Protein 1 / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D051782:Sterol Regulatory Element Binding Protein 2 / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D019014:fas Receptor / Q000235:genetics / Q000378:metabolism
chemical_list: C491901:FAS protein, human; D005227:Fatty Acids; C000599408:HMGCS2 protein, human; D017879:Isothiocyanates; C497387:SREBF1 protein, human; C497390:SREBF2 protein, human; D051780:Sterol Regulatory Element Binding Protein 1; D051782:Sterol Regulatory Element Binding Protein 2; D019014:fas Receptor; C041942:2,3,4-tri-O-acetylarabinopyranosyl isothiocyanate; D002784:Cholesterol; C553220:HMGCR protein, human; D006903:Hydroxymethylglutaryl CoA Reductases; D008156:Luciferases; C523776:SCD1 protein, human; D013230:Stearoyl-CoA Desaturase; D006904:Hydroxymethylglutaryl-CoA Synthase; C000588423:ACACA protein, human; D000103:Acetyl-CoA Carboxylase
keywords: SREBP; allyl isothiocyanate; cholesterol; fatty acid