geoscience.net logo
+ Resolve Article
+ Follow Us
Follow on FacebookFollow on Facebook
Follow on TwitterFollow on Twitter

+ Translate
+ Subscribe to Site Feed
GeoScience Most Shared ContentMost Shared Content

High-affinity binding sites for oxygenated sterols in rat liver microsomes: possible identity with antiestrogen binding sites


, : High-affinity binding sites for oxygenated sterols in rat liver microsomes: possible identity with antiestrogen binding sites. Biochimica et Biophysica Acta 1033(2): 154-161

Oxygenated derivatives of cholesterol are known to exhibit a number of biological activities including the inhibition of cholesterol biosynthesis and of cell proliferation, but their mechanism of action remains unclear. Previous studies have identified a cytosolic protein which binds 25-hydroxycholesterol, as well as several other oxysterols, with high affinity, possibly mediating some of their effects. We now report the existence of a high-affinity oxysterol binding site in rat liver microsomes which is distinct from the cytosolic binding protein. Among the oxygenated sterols examined, 5 alpha-cholestan-3 beta-ol-7-one (7-ketocholestanol) had the highest affinity for this microsomal binding site (Kd = 2.7 nM). Using 7-keto[3H]cholestanol as the radioactive ligand, we found that binding of this oxysterol to the microsomal binding site was saturable and reversible and was displaceable by the following oxysterols in descending order of potency: 7-ketocholestanol greater than 6-ketocholestanol greater than 7 beta-hydroxycholesterol = 7-ketocholesterol greater than cholesten-3 beta,5 alpha, 6 beta-triol = 7 alpha-hydroxycholesterol greater than 4-cholesten-3-one. All other sterols studied, including, notably, 25-hydroxycholesterol, had little or no inhibitory effect on 7-keto[3H]cholestanol binding. Additional studies revealed that the microsomal oxysterol binding site was probably identical to the antiestrogen binding site described by other workers. First, saturation analysis and kinetic studies demonstrated that the antiestrogen tamoxifen competed directly with 7-keto[3H]cholestanol for the same binding site. Second, the ability of different oxysterols and antiestrogens to inhibit 7-keto[3H]cholestanol binding to the microsomal binding site paralleled their ability to inhibit [3H]tamoxifen binding to the antiestrogen binding site. Third, the tissue distribution of binding sites for 7-keto[3H]cholestanol was similar to that of the antiestrogen binding site. We conclude that: (1) in rat liver microsomes there are high-affinity oxysterol binding sites whose ligand specificity is different from that of the cytosolic oxysterol binding protein; and (2) the microsomal oxysterol binding site is probably identical to the antiestrogen binding site. The biological significance of these observations remains to be explored.

US$29.90

PMID: 2306459


Other references

Stary, J.K.atzer, K1; Prasilova, J., 1982: The cumulation of methylmercury and phenylmercury species on alga Chlorella kessleri. Journal of the Indian Chemical Society 59(11-12): 1329-1330

Solomon, B.D.; Muenke, M., 2013: When to suspect a genetic syndrome. Family physicians should be able to recognize findings on physical examination and history that suggest the presence of a genetic syndrome to aid in the diagnosis and treatment of potentially affected patients, as well as subspecialty referral. Ge...

Darcy, I.K.; Scharein, R.G., 2006: TopoICE-R: 3D visualization modeling the topology of DNA recombination. TopoICE-R is a three-dimensional visualization and manipulation software for solving 2-string tangle equations and can be used to model the topology of DNA bound by proteins such as recombinases and topoisomerases. This software, manual and exampl...

Rourke A.W., 1974: Myosin synthesis in normal and hypertrophying chicken pectoralis. Federation Proceedings 33(5 PART 2): 1521

Wilson, M.R.; Patel, J.G.; Coleman, A.; McDade, C.L.; Stanford, R.H.; Earnshaw, S.R., 2017: Cost-effectiveness analysis of umeclidinium/vilanterol for the management of patients with moderate to very severe COPD using an economic model. Bronchodilators such as long-acting muscarinic antagonists (LAMAs) and long-acting β<sub>2</sub>-agonists (LABAs) are central to the pharmacological management of COPD. Dual bronchodilation with umeclidinium/vilanterol (UMEC/VI; 62.5/...

Brummelman, E.; Thomaes, S., 2017: How Children Construct Views of Themselves: A Social-Developmental Perspective. As they grow up, children construct views of themselves and their place in the world, known as their self-concept. This topic has often been addressed by social psychologists (studying how the self-concept is influenced by social contexts) and dev...

Martinez-Iglesias, J.C., 1986: Decapod crustaceans of the gulf of batabano cuba caridea and penaeidea. Results of the systematic study of shrimps in samples from dredges of 23 stations at the Batabano Gulf. Cuba, are presented. These include diagnoses and figures of 28 species, belonging to 18 genera and 7 families. Twelve species [Alpheus armillat...

Wang Zheng; Bao FuCheng; Guo WenJing, 2003: The effect of the process factors on the properties of wood-plastics composite panels. The influence of the process factors on the physical-mechanical properties of wood plastic composite panels made from Masson pine (Pinus massoniana) and poplar (Populus sp.) were studied. Three plastics (polyethylene, polypropylene and polysterene...

Moscariello, A.; Kolkman, W.; Seifert, D.; Foreste, K., 2008: Reservoir modeling of Lower Devonian tight gas reservoirs in the Zerafa Block, Western Desert, Algeria; a workflow from geological concepts to 3-D models. The Lower Devonian clastic reservoirs in the northern Zerafa block (Western Desert, Algeria) are relatively unexplored, while some of the existing discoveries seem to be tight gas reservoirs. The reservoir consists of shallow- marine clastic seque...

Mehta, P.A.; McDonagh, S.; Phillips, J.; Grocott-Mason, R.; Dubrey, S.W., 2009: Angiotensin receptor blocker therapy for heart failure patients: is combination treatment a feasible prospect?. The addition of the angiotensin II type 1 receptor blocker (ARB) candesartan to a angiotensin-converting enzyme inhibitor (ACEI) has been associated with improved clinical outcomes in patients with heart failure. However many do not tolerate combi...