title: Low level of hydrogen peroxide induces lipid synthesis in BRL-3A cells through a CAP-independent SREBP-1a activation.
abstract: Although H2O2 is traditionally known to have cytotoxic effects, recent studies argue about its regulatory role on lipid metabolism. However, the mechanism underlying the induction of lipid biosynthesis by oxidative stress still remains unknown. To shed light on this aspect we investigated the H2O2-induced lipogenesis in rat liver BRL-3A cells. We found that a short-term exposition of cells to 35μM H2O2 didn't cause any significant sign of cell damage measured by following diene formation and lactate dehydrogenase release from cells. However, in this stressful condition, a significant increase of [1-(14)C]acetate incorporation into fatty acids and cholesterol, associated to an increase in the activity and expression of key enzymes of fatty acid and cholesterol synthesis, were measured. mRNA and protein contents of the transcription factors SREBP-1 and SREBP-2, involved in the activation of lipid synthesis, increased as well. The analysis of molecular mechanism of SREBP-1 activation revealed, in treated compared to control cells, a higher SREBP-1a mRNA translation involving an internal ribosome entry side (IRES), present in the leader region of its mRNA. Longer exposition to the pro-oxidant induced a progressive loss of cell viability together with an increase of cell triacylglycerol content.
authors.affiliation: Laboratory of Biochemistry and Molecular Biology, Department of Biological and Environmental Sciences and Technologies, University of Salento, Via Prov.le Lecce-Monteroni, 73100 Lecce, Italy.
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Giudetti
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Damiano
authors.forename: Gabriele Vincenzo
authors.initials: GV
authors.lastname: Gnoni
authors.forename: Luisa
authors.initials: L
authors.lastname: Siculella
mesh_terms: D000818:Animals; D002460:Cell Line; D002470:Cell Survival; D002784:Cholesterol / Q000096:biosynthesis*; D004789:Enzyme Activation; D064429:Fatty Acid Synthases; D005227:Fatty Acids / Q000096:biosynthesis*; D022781:Hepatocytes / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism*; D050356:Lipid Metabolism / Q000235:genetics; D018384:Oxidative Stress; D014176:Protein Biosynthesis; D039381:RNA Cap-Binding Proteins / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017382:Reactive Oxygen Species; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics / Q000378:metabolism*; D051782:Sterol Regulatory Element Binding Protein 2 / Q000235:genetics / Q000378:metabolism*; D014280:Triglycerides / Q000096:biosynthesis
chemical_list: D005227:Fatty Acids; D039381:RNA Cap-Binding Proteins; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D051780:Sterol Regulatory Element Binding Protein 1; D051782:Sterol Regulatory Element Binding Protein 2; D014280:Triglycerides; D002784:Cholesterol; D006861:Hydrogen Peroxide; D064429:Fatty Acid Synthases