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dc.contributor.authorBerkhout, Theo
dc.contributor.authorHavekes, Louis M.
dc.contributor.authorPearce, N. J.
dc.contributor.authorGroot, P.H.E.
dc.date.accessioned2014-06-11T09:00:32Z
dc.date.available2014-06-11T09:00:32Z
dc.date.issued1990
dc.identifier.citationBerkhout , 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.issn0264-6021
dc.identifier.otherPURE: 7130850
dc.identifier.otherPURE UUID: 206347e4-44eb-4195-8792-06f2fcd3cfc4
dc.identifier.otherScopus: 0025251789
dc.identifier.urihttp://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 drugsen
dc.language.isoeng
dc.relation.ispartofBiochemical Journal
dc.titleThe 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 G2en
dc.contributor.institutionSchool of Life and Medical Sciences
dc.contributor.institutionDepartment of Pharmacy
dc.contributor.institutionHealth & Human Sciences Research Institute
dc.contributor.institutionMedicinal and Analytical Chemistry
dc.description.statusPeer reviewed
dc.relation.schoolSchool of Life and Medical Sciences
dcterms.dateAccepted1990
rioxxterms.typeJournal Article/Review
herts.preservation.rarelyaccessedtrue


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