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  • Title: L-cysteine down-regulates SREBP-1c-regulated lipogenic enzymes expression via glutathione in HepG2 cells.
    Author: Bettzieche A, Brandsch C, Hirche F, Eder K, Stangl GI.
    Journal: Ann Nutr Metab; 2008; 52(3):196-203. PubMed ID: 18544973.
    Abstract:
    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.
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