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 CuSO4 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.

Keywords:
L-Cysteine, Sterol regulatory element-binding protein-1c, Lipogenic enzymes, Glutathione, HepG2 cells
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© 2008 S. Karger AG, Basel
2008
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