L-cysteine down-regulates SREBP-1c-regulated lipogenic enzymes expression via glutathione in HepG2 cells.
OBJECTIVE
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.
Institute of Agricultural and Nutritional Sciences, Martin Luther University Halle-Wittenberg, Halle/Saale, Germany.
Anja
A
Bettzieche
Corinna
C
Brandsch
Frank
F
Hirche
Klaus
K
Eder
Gabriele I
GI
Stangl
D045744:Cell Line, Tumor; D003545:Cysteine / Q000494:pharmacology*; D015536:Down-Regulation; D064429:Fatty Acid Synthases / Q000235:genetics / Q000378:metabolism; D005954:Glucosephosphate Dehydrogenase / Q000235:genetics / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism*; D006801:Humans; D050356:Lipid Metabolism; D008099:Liver / Q000201:enzymology*; D012333:RNA, Messenger / Q000096:biosynthesis; D013230:Stearoyl-CoA Desaturase / Q000235:genetics / Q000378:metabolism; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics / Q000378:metabolism*
D012333:RNA, Messenger; D051780:Sterol Regulatory Element Binding Protein 1; D005954:Glucosephosphate Dehydrogenase; D013230:Stearoyl-CoA Desaturase; D064429:Fatty Acid Synthases; D005978:Glutathione; D003545:Cysteine