Green tea upregulates the low-density lipoprotein receptor through the sterol-regulated element binding Protein in HepG2 liver cells.
Green tea from Camellia sinensis lowers plasma cholesterol in animal models of hypercholesterolemia. The aim of this study was to determine the effects of green tea on the expression of the hepatic low-density lipoprotein (LDL) receptor, a cell surface protein involved in the control of plasma cholesterol. Incubating human HepG2 liver cells in culture with green tea increased both LDL receptor binding activity and protein. An ethyl acetate extract of green tea, containing 70% (w/w) catechins, also increased the LDL receptor binding activity, protein, and mRNA, indicating that (1) the effect was at the level of gene transcription and that (2) the catechins were the active constituents. The mechanism by which green tea up-regulated the LDL receptor was then investigated. Green tea decreased the cell cholesterol concentration (-30%) and increased the conversion of the sterol-regulated element binding protein (SREBP-1) from the inactive precursor form to the active transcription-factor form. Consistent with this, the mRNA of 3-hydroxy-3-methylglutaryl coenzyme A reductase, the rate-limiting enzyme in cholesterol synthesis, was also increased by green tea. In conclusion, green tea up-regulated the LDL receptor in HepG2 cells. The effect was most likely mediated through SREBP-1 in response to a decrease in the intracellular cholesterol concentration. The LDL receptor may therefore play a role in the hypocholesterolemic effect of green tea in vivo.
Bursill
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CSIRO Health Sciences and Nutrition, Adelaide, SA 5000, Australia.
Roach
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Bottema
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Pal
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D000818:Animals; D022762:CCAAT-Enhancer-Binding Proteins / Q000502:physiology*; D002460:Cell Line; D002635:Chenodeoxycholic Acid / Q000096:biosynthesis; D002784:Cholesterol / Q000096:biosynthesis; D004268:DNA-Binding Proteins / Q000502:physiology*; D011973:Receptors, LDL / Q000502:physiology*; D051780:Sterol Regulatory Element Binding Protein 1; D013662:Tea; D014157:Transcription Factors; D015854:Up-Regulation / Q000502:physiology*
D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; D011973:Receptors, LDL; D051780:Sterol Regulatory Element Binding Protein 1; D013662:Tea; D014157:Transcription Factors; D002635:Chenodeoxycholic Acid; D002784:Cholesterol