dc.contributor.author | Berkhout, Theo | |
dc.contributor.author | Havekes, Louis M. | |
dc.contributor.author | Pearce, N. J. | |
dc.contributor.author | Groot, P.H.E. | |
dc.date.accessioned | 2014-06-11T09:00:32Z | |
dc.date.available | 2014-06-11T09:00:32Z | |
dc.date.issued | 1990 | |
dc.identifier.citation | Berkhout , T , Havekes , L M , Pearce , N J & Groot , P H E 1990 , ' The effect of (-)-hydroxycitrate on the activity of the low-density-lipoprotein receptor and 3-hydroxy-3-methylglutaryl-CoA reductase levels in the human hepatoma cell line Hep G2 ' , Biochemical Journal , vol. 272 , no. 1 , pp. 181-186 . | |
dc.identifier.issn | 0264-6021 | |
dc.identifier.uri | http://hdl.handle.net/2299/13688 | |
dc.description.abstract | (-)-Hydroxycitrate, a potent inhibitor of ATP citrate-lyase, was tested in Hep G2 cells for effects on cholesterol homoeostasis. After 2.5 h and 18 h incubations with (-)-hydroxycitrate at concentrations of 0.5 mM or higher, incorporation of [1,5-14C]citrate into fatty acids and cholesterol was strongly inhibited. This most likely reflects an effective inhibition of ATP citrate-lyase. Cholesterol biosynthesis was decreased to 27% of the control value as measured by incorporations from 3H2O, indicating a decreased flux of carbon units through the cholesterol-synthetic pathway. After 18 h preincubation with 2 mM-(-)-hydroxycitrate, the cellular low-density-lipoprotein (LDL) receptor activity was increased by 50%, as determined by the receptor-mediated association and degradation. Measurements of receptor-mediated binding versus LDL concentration suggests that this increase was due to an increase in the numbers of LDL receptors. Simultaneously, enzyme levels of 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase as determined by activity measurements increased 30-fold. Our results suggest that the increases in HMG-CoA reductase and the LDL receptor are initiated by the decreased flux of carbon units in the cholesterol-synthetic pathway, owing to inhibition of ATP citratelyase. A similar induction of HMG-CoA reductase and LDL receptor was also found after preincubations of cells with 0.3 microM-mevinolin, suggesting that the underlying mechanism for this induction is identical for both drugs | en |
dc.language.iso | eng | |
dc.relation.ispartof | Biochemical Journal | |
dc.title | The effect of (-)-hydroxycitrate on the activity of the low-density-lipoprotein receptor and 3-hydroxy-3-methylglutaryl-CoA reductase levels in the human hepatoma cell line Hep G2 | en |
dc.contributor.institution | School of Life and Medical Sciences | |
dc.contributor.institution | Department of Pharmacy | |
dc.contributor.institution | Health & Human Sciences Research Institute | |
dc.contributor.institution | Medicinal and Analytical Chemistry | |
dc.description.status | Peer reviewed | |
rioxxterms.type | Journal Article/Review | |
herts.preservation.rarelyaccessed | true | |