BACKGROUND/AIM: Protein-associated amino acids are supposed to play a role in sterol regulatory element-binding protein (SREBP)-mediated regulation of lipid metabolism. This study investigates the effects of cysteine on expression of SREBP-regulated hepatic genes. METHODS: HepG2 cells which are an accepted model for the study of the lipid metabolism were treated with L-cysteine under different conditions. RESULTS: Exposure of cells to L-cysteine reduced the mRNA concentrations of SREBP-1c (-35 to -43%) and its target genes fatty acid synthase (FAS; -20 to -50%), glucose-6-phosphate-dehydrogenase (G6PDH; -31 to -35%), and stearoyl-coenzyme A desaturase (SCD)1 (-34 to -50%). Cells treated with L-cysteine had 47% higher glutathione and 47% lower triglyceride concentrations than control cells. In cells which were concurrently treated with L-cysteine and L-buthionine-[S,R]-sulfoximine, an inhibitor of enzymatic glutathione synthesis, no down-regulation of the gene expression was observed. Pro-oxidant CuSO(4) up-regulated SREBP-1c (+71%), FAS (+165%), G6PDH (+84%) and SCD1 (+96%) mRNA abundance compared to control cells, but when cells were concurrently treated with L-cysteine, the gene expression remained at control level. CONCLUSIONS: The results show that L-cysteine rapidly down-regulates the transcription of genes involved in fatty acid biosynthesis via a mechanism that appears to be mediated by an improved glutathione status. (c) 2008 S. Karger AG, Basel.
BACKGROUND/AIM: Protein-associated amino acids are supposed to play a role in sterol regulatory element-binding protein (SREBP)-mediated regulation of lipid metabolism. This study investigates the effects of cysteine on expression of SREBP-regulated hepatic genes. METHODS: HepG2 cells which are an accepted model for the study of the lipid metabolism were treated with L-cysteine under different conditions. RESULTS: Exposure of cells to L-cysteine reduced the mRNA concentrations of SREBP-1c (-35 to -43%) and its target genes fatty acid synthase (FAS; -20 to -50%), glucose-6-phosphate-dehydrogenase (G6PDH; -31 to -35%), and stearoyl-coenzyme A desaturase (SCD)1 (-34 to -50%). Cells treated with L-cysteine had 47% higher glutathione and 47% lower triglyceride concentrations than control cells. In cells which were concurrently treated with L-cysteine and L-buthionine-[S,R]-sulfoximine, an inhibitor of enzymatic glutathione synthesis, no down-regulation of the gene expression was observed. Pro-oxidant CuSO(4) up-regulated SREBP-1c (+71%), FAS (+165%), G6PDH (+84%) and SCD1 (+96%) mRNA abundance compared to control cells, but when cells were concurrently treated with L-cysteine, the gene expression remained at control level. CONCLUSIONS: The results show that L-cysteine rapidly down-regulates the transcription of genes involved in fatty acid biosynthesis via a mechanism that appears to be mediated by an improved glutathione status. (c) 2008 S. Karger AG, Basel.
Authors: Indrani Sinha-Hikim; Amiya P Sinha-Hikim; Ruoqing Shen; Hyun Ju Kim; H Kim; Samuel W French; Nosratola D Vaziri; Nosratola D Vaziri; Albert C Crum; Albert Crum; Tripathi B Rajavashisth; Keith C Norris Journal: Exp Mol Pathol Date: 2011-05-03 Impact factor: 3.362