title: Effects of retinoic acid and hydrogen peroxide on sterol regulatory element-binding protein-1a activation during adipogenic differentiation of 3T3-L1 cells.
abstract: Both retinoic acid (RA) and oxidative stress (H2O2) increased transcription and cleavage of membrane-bound sterol regulatory element-binding protein (SREBP)-1, leading to enhanced transcription of fatty acid synthase (FAS) in hepatoma cells. On the other hand, RA and H2O2 decreased and increased lipogenesis in adipocytes, respectively, although roles of SREBP-1 activation in these effects remain to be elucidated. To elucidate its involvement, we examined the activation of SREBP-la, expression of FAS genes and lipid accumulation in 3T3-L1 cells in the presence of RA and/or H2O2. RA (1 microM) treatment suppressed expression of SREBP-1a and FAS genes and lipid accumulation. H2O2 (2 microM) treatment induced increased cleavage of SREBP-1a, without affecting amounts of SREBP-1a mRNA and precursor protein, and enhanced expression of FAS gene and lipid accumulation. Increased cleavage of SREBP-1a by H2O2 was also observed even in the presence of RA. These results suggest that H2O2, enhances a cleavage of SREBP-1a precursor protein, which independently occurs with the RA suppression of SREBP-1a gene expression, and that RA itself has no role in the SREBP-1a activation in adipocytes.
authors.affiliation: Laboratory of Biochemistry, Department of Biomedical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo 060-0818, Japan.
authors.forename: Mabrouk A
authors.initials: MA
authors.lastname: Abd Eldaim
authors.forename: Yuko
authors.initials: Y
authors.lastname: Okamatsu-Ogura
authors.forename: Akira
authors.initials: A
authors.lastname: Terao
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Kimura
mesh_terms: D041721:3T3-L1 Cells / Q000166:cytology* / Q000187:drug effects; D000199:Actins / Q000187:drug effects / Q000235:genetics; D017667:Adipocytes / Q000166:cytology* / Q000187:drug effects; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects*; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D051379:Mice; D016133:Polymerase Chain Reaction; D051780:Sterol Regulatory Element Binding Protein 1 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D014212:Tretinoin / Q000494:pharmacology*; D019014:fas Receptor / Q000187:drug effects / Q000235:genetics
chemical_list: D000199:Actins; C491899:Fas protein, mouse; D051780:Sterol Regulatory Element Binding Protein 1; D019014:fas Receptor; D014212:Tretinoin; D006861:Hydrogen Peroxide