Document Detail


L-cysteine down-regulates SREBP-1c-regulated lipogenic enzymes expression via glutathione in HepG2 cells.
MedLine Citation:
PMID:  18544973     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Anja Bettzieche; Corinna Brandsch; Frank Hirche; Klaus Eder; Gabriele I Stangl
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Publication Detail:
Type:  Journal Article     Date:  2008-06-11
Journal Detail:
Title:  Annals of nutrition & metabolism     Volume:  52     ISSN:  1421-9697     ISO Abbreviation:  Ann. Nutr. Metab.     Publication Date:  2008  
Date Detail:
Created Date:  2008-07-11     Completed Date:  2008-09-03     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  8105511     Medline TA:  Ann Nutr Metab     Country:  Switzerland    
Other Details:
Languages:  eng     Pagination:  196-203     Citation Subset:  IM    
Copyright Information:
(c) 2008 S. Karger AG, Basel.
Affiliation:
Institute of Agricultural and Nutritional Sciences, Martin Luther University Halle-Wittenberg, Halle/Saale, Germany.
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MeSH Terms
Descriptor/Qualifier:
Cell Line, Tumor
Cysteine / pharmacology*
Down-Regulation*
Fatty Acid Synthetase Complex / genetics,  metabolism
Glucosephosphate Dehydrogenase / genetics,  metabolism
Glutathione / metabolism*
Humans
Lipid Metabolism
Liver / enzymology*
RNA, Messenger / biosynthesis
Stearoyl-CoA Desaturase / genetics,  metabolism
Sterol Regulatory Element Binding Protein 1 / genetics,  metabolism*
Chemical
Reg. No./Substance:
0/RNA, Messenger; 0/Sterol Regulatory Element Binding Protein 1; 52-90-4/Cysteine; 70-18-8/Glutathione; EC 1.1.1.49/Glucosephosphate Dehydrogenase; EC 1.14.19.1/Stearoyl-CoA Desaturase; EC 6.-/Fatty Acid Synthetase Complex

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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