A specific hydroxysterol binding protein in human lymphocyte cytosol.
A discriminating system capable of recognizing the oxygenated sterols was investigated in human lymphocytes. After labelling entire cells with 25-hydroxy [3H] cholesterol (10 nM) the cytosol was ultracentrifuged on a linear sucrose density gradient. Bound 25-hydroxy [3H] cholesterol was located in a single peak with a sedimentation coefficient of 8.3 S. Pronase treatment abolished the radioactive peak. This 8.3 S protein had a low binding capacity for 25-hydroxy [3H] cholesterol and probably a high affinity. This last parameter was not determined on account of some difficulties encountered in a cell-free system relating to the physico-chemical properties of 25-hydroxycholesterol. Only the hydroxylated sterols closely related to 25-hydroxycholesterol were capable of specifically binding to the 8.3 S protein, in contrast with cholesterol. This protein differed from the binding proteins of oxygenated derivatives of vitamin D3 and glucocorticoids. With the human lymphocyte as a model and under our experimental conditions, this hydroxylated sterol-binding protein seems to be involved rather in the cell division control than in the regulation of HMG-CoA reductase activity: indeed, the hydroxysterols able to inhibit thymidine [3H] incorporation into DNA are recognized by this protein whereas the hydroxysterols active on HMG-CoA reductase activity without affecting thymidine [3H] incorporation into DNA are not.
D002352:Carrier Proteins / Q000097:blood*; D002455:Cell Division; D003600:Cytosol / Q000378:metabolism; D006801:Humans; D006888:Hydroxycholesterols / Q000378:metabolism; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D025782:Hydroxymethylglutaryl-CoA-Reductases, NADP-dependent; D006914:Hydroxysteroids / Q000378:metabolism* / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D008214:Lymphocytes / Q000166:cytology / Q000378:metabolism*; D013329:Structure-Activity Relationship; D009124:Muscle Proteins; D047908:Intracellular Signaling Peptides and Proteins; D060588:LIM Domain Proteins
D002352:Carrier Proteins; D006888:Hydroxycholesterols; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D025782:Hydroxymethylglutaryl-CoA-Reductases, NADP-dependent; D006914:Hydroxysteroids; C007997:25-hydroxycholesterol; C101149:FHL1 protein, human; D009124:Muscle Proteins; D047908:Intracellular Signaling Peptides and Proteins; D060588:LIM Domain Proteins