title: Cruciferous vegetable phytochemical sulforaphane affects phase II enzyme expression and activity in rat cardiomyocytes through modulation of Akt signaling pathway.
abstract: The isothiocyanate sulforaphane (SF), abundant in Cruciferous vegetables, is known to induce antioxidant/detoxification enzymes in many cancer cell lines, but studies focused on its cytoprotective action in nontransformed cells are just at the beginning. Since we previously demonstrated that SF elicits cardioprotection through an indirect antioxidative mechanism, the aim of this study was to analyze the signaling pathways through which SF exerts its protective effects. Using cultured rat cardiomyocytes, we investigated the ability of SF to activate Akt/protein kinase B (PKB) and extracellular signal-regulated kinase 1 and 2 (ERK1/2) signaling pathways, which are implicated in cardiac cell survival, and to increase the phosphorylation of Nuclear factor E2-related factor 2 (Nrf2) and its binding to the antioxidant response element. By means of specific inhibitors, we demonstrated that the Phosphatidylinositol 3-kinase (PI3K)/Akt pathway represents a mechanism through which SF influences both expression and activity of glutathione reductase, glutathione-S-transferase, thioredoxin reductase, and NAD(P)H:quinone oxidoreductase-1, analyzed by western immunoblotting and spectrophotometric assay, respectively, and modulates Nrf2 binding and phosphorylation resulting in a cytoprotective action against oxidative damage. Results of this study confirm the importance of phase II enzymes modulation as cytoprotective mechanism and support the nutritional assumption of Cruciferous vegetables as source of nutraceutical cardioprotective agents.
authors.affiliation: Dept of Biochemistry G Moruzzi, Alma Mater Studiorum-Univ of Bologna, Via Irnerio 48, 40126 Bologna, Italy.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Leoncini
authors.forename: Marco
authors.initials: M
authors.lastname: Malaguti
authors.forename: Cristina
authors.initials: C
authors.lastname: Angeloni
authors.forename: Elisa
authors.initials: E
authors.lastname: Motori
authors.forename: Daniele
authors.initials: D
authors.lastname: Fabbri
authors.forename: Silvana
authors.initials: S
authors.lastname: Hrelia
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D019607:Brassicaceae / Q000737:chemistry*; D002478:Cells, Cultured; D004789:Enzyme Activation / Q000187:drug effects; D005980:Glutathione Reductase / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D017879:Isothiocyanates; D050217:Metabolic Detoxication, Phase II; D032383:Myocytes, Cardiac / Q000201:enzymology*; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects*; D013454:Sulfoxides; D013861:Thiocyanates / Q000494:pharmacology*; D013880:Thioredoxin-Disulfide Reductase / Q000378:metabolism
chemical_list: D017879:Isothiocyanates; D051267:NF-E2-Related Factor 2; D013454:Sulfoxides; D013861:Thiocyanates; D016660:NAD(P)H Dehydrogenase (Quinone); D005980:Glutathione Reductase; D013880:Thioredoxin-Disulfide Reductase; D005982:Glutathione Transferase; D051057:Proto-Oncogene Proteins c-akt; C016766:sulforaphane