The Experts below are selected from a list of 66 Experts worldwide ranked by ideXlab platform
Kjell Wikvall - One of the best experts on this subject based on the ideXlab platform.
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7α hydroxylation of 26 Hydroxycholesterol 3β hydroxy 5 cholestenoic acid and 3β hydroxy 5 cholenoic acid by cytochrome p 450 in pig liver microsomes
FEBS Letters, 1992Co-Authors: Anders Toll, Junichi Shoda, Magnus Axelson, Jan Sjovall, Kjell WikvallAbstract:Pig liver microsomes were found to catalyze the 7α-hydroxylation of several potential bile acid precursors besides cholesterol. 26-Hydroxycholesterol, 3β-hydroxy-5-cholestenoic acid and 3β-hydroxy-5-cholenoic acid were all efficiently converted into the 7α-hydroxylated products. Two cytochrome P-450 fractions showing 7α-hydroxylase activity could be isolated. One fraction catalyzed 7α-hydroxylation of 26-Hydroxycholesterol. 3β-hydroxy-5-cholestenoic acid and 3β-hydroxy-5-cholenoic acid but was inactive towards cholesterol. The other fraction catalyzed 7α-hydroxylation of cholesterol in addition to the other substrates. 26-Hydroxycholesterol in equimolar concentration did not inhibit the cholesterol 7α-hydroxylase activity of this fraction. It is concluded that liver microsomes contain a cytochrome P-450 catalyzing 7α-hydroxylation of 26-Hydroxycholesterol, 3β-hydroxy-5-cholestenoic acid and 3β-hydroxy-5-cholenoic acid. The results indicate that this cytochrome P-450 is different from that catalyzing 7α-hydroxylation of cholesterol.
Anders Toll - One of the best experts on this subject based on the ideXlab platform.
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7α hydroxylation of 26 Hydroxycholesterol 3β hydroxy 5 cholestenoic acid and 3β hydroxy 5 cholenoic acid by cytochrome p 450 in pig liver microsomes
FEBS Letters, 1992Co-Authors: Anders Toll, Junichi Shoda, Magnus Axelson, Jan Sjovall, Kjell WikvallAbstract:Pig liver microsomes were found to catalyze the 7α-hydroxylation of several potential bile acid precursors besides cholesterol. 26-Hydroxycholesterol, 3β-hydroxy-5-cholestenoic acid and 3β-hydroxy-5-cholenoic acid were all efficiently converted into the 7α-hydroxylated products. Two cytochrome P-450 fractions showing 7α-hydroxylase activity could be isolated. One fraction catalyzed 7α-hydroxylation of 26-Hydroxycholesterol. 3β-hydroxy-5-cholestenoic acid and 3β-hydroxy-5-cholenoic acid but was inactive towards cholesterol. The other fraction catalyzed 7α-hydroxylation of cholesterol in addition to the other substrates. 26-Hydroxycholesterol in equimolar concentration did not inhibit the cholesterol 7α-hydroxylase activity of this fraction. It is concluded that liver microsomes contain a cytochrome P-450 catalyzing 7α-hydroxylation of 26-Hydroxycholesterol, 3β-hydroxy-5-cholestenoic acid and 3β-hydroxy-5-cholenoic acid. The results indicate that this cytochrome P-450 is different from that catalyzing 7α-hydroxylation of cholesterol.
Norman B. Javitt - One of the best experts on this subject based on the ideXlab platform.
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breast cancer and 25r 26 Hydroxycholesterol
Steroids, 2015Co-Authors: Norman B. JavittAbstract:(25R)-26-Hydroxycholesterol (27-Hydroxycholesterol) has been found to accumulate in breast tissue and to stimulate tumor growth via the estrogen receptor. Although most tissues express CYP27A1, the highest levels are in macrophages and most attention had been given to the production of 27-Hydroxycholesterol in sub-endothelial macrophages as part of reverse cholesterol transport. In view of the newly identified biologic activity, it is important to consider the determinants of the levels of 27-Hydroxycholesterol in macrophages that infiltrate breast tissue. Among these determinants are the oxysterol binding proteins expressed in macrophages, the level of expression of CYP7B1, the oxysterol 7 alpha hydroxylase that generates an inactive triol, and further oxidation of 27-hydroxycholestrol to the C27 acid by multifunctional CYP27A1. Transport of 27-Hydroxycholesterol from macrophages to plasma is HDL-associated. In many tissues the ratio of 27-Hydroxycholesterol to cholesterol (ng/μg) is higher than that in plasma. Tamoxifen, an effective estrogen receptor antagonist that prevents breast cancer, also has the biologic property of blocking several steps in the lanosterol to cholesterol metabolic pathway. In genetically disposed women, tamoxifen may increase the amount of 27-Hydroxycholesterol in breast tissue.
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25r 26 Hydroxycholesterol revisited synthesis metabolism and biologic roles
Journal of Lipid Research, 2002Co-Authors: Norman B. JavittAbstract:The CYP27 gene is expressed in arterial endothelium, macrophages, and other tissues. The gene product generates sterol intermediates that function as ligands for nuclear receptors prior to their transport to the liver for metabolism, mostly to bile acids. Most attention has been given to 27-Hydroxycholesterol as a ligand for LXR activated receptors and to chenodeoxycholic acid as a ligand for farnesoid X activated receptors (FXRs). Expression of the pathway in macrophages is essential for normal reverse cholesterol transport. Thus, ABC transporter activity is upregulated, which enhances cholesterol efflux. Absence of these mechanisms probably accounts for the accelerated atherosclerosis that occurs in cerebrotendinous xanthomatosis. Accumulation of 27-Hydroxycholesterol in human atheroma is puzzling and may reflect low levels of oxysterol 7alpha-hydroxylase activity in human macrophages. The same enzyme determines the proportion of mono-, di-, and tri-hydroxy bile acids synthesized in the liver. Oxysterol 7alpha-hydroxylase deficiency is a molecular basis for cholestatic liver disease. Chenodeoxycholic acid, the major normal end product, downregulates expression of cholesterol 7alpha-hydroxylase via the FXR/short heterodimer protein nuclear receptor and thus limits total bile acid production. The challenge is to quantify in a physiologic setting the magnitude of the pathway in different tissues and to further evaluate the biologic roles of all the intermediates that may function as ligands for orphan nuclear receptors or via other regulatory mechanisms.
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biologic role s of the 25 r 26 Hydroxycholesterol metabolic pathway
Biochimica et Biophysica Acta, 2000Co-Authors: Norman B. JavittAbstract:Abstract Expression of the gene coding for the synthesis of 25(R),26-Hydroxycholesterol in many tissues and the finding that this sterol can be the sole pathway for the production of bile acids have led to a renewed interest in this metabolic pathway. A further impetus for exploring the normal biologic roles that are served by expression of the CYP27A1 gene is the knowledge that mutations in humans are associated with accelerated atherosclerosis and with severe neurologic impairment. The molecular mechanisms governing these phenotypic expressions are not known but in light of the traditional role of steroids as ligands for receptors that regulate gene expression it seems likely that the intermediates in this pathway modulate a number of enzymatic activities that remain to be elucidated.
Magnus Axelson - One of the best experts on this subject based on the ideXlab platform.
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7α hydroxylation of 26 Hydroxycholesterol 3β hydroxy 5 cholestenoic acid and 3β hydroxy 5 cholenoic acid by cytochrome p 450 in pig liver microsomes
FEBS Letters, 1992Co-Authors: Anders Toll, Junichi Shoda, Magnus Axelson, Jan Sjovall, Kjell WikvallAbstract:Pig liver microsomes were found to catalyze the 7α-hydroxylation of several potential bile acid precursors besides cholesterol. 26-Hydroxycholesterol, 3β-hydroxy-5-cholestenoic acid and 3β-hydroxy-5-cholenoic acid were all efficiently converted into the 7α-hydroxylated products. Two cytochrome P-450 fractions showing 7α-hydroxylase activity could be isolated. One fraction catalyzed 7α-hydroxylation of 26-Hydroxycholesterol. 3β-hydroxy-5-cholestenoic acid and 3β-hydroxy-5-cholenoic acid but was inactive towards cholesterol. The other fraction catalyzed 7α-hydroxylation of cholesterol in addition to the other substrates. 26-Hydroxycholesterol in equimolar concentration did not inhibit the cholesterol 7α-hydroxylase activity of this fraction. It is concluded that liver microsomes contain a cytochrome P-450 catalyzing 7α-hydroxylation of 26-Hydroxycholesterol, 3β-hydroxy-5-cholestenoic acid and 3β-hydroxy-5-cholenoic acid. The results indicate that this cytochrome P-450 is different from that catalyzing 7α-hydroxylation of cholesterol.
Junichi Shoda - One of the best experts on this subject based on the ideXlab platform.
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7α hydroxylation of 26 Hydroxycholesterol 3β hydroxy 5 cholestenoic acid and 3β hydroxy 5 cholenoic acid by cytochrome p 450 in pig liver microsomes
FEBS Letters, 1992Co-Authors: Anders Toll, Junichi Shoda, Magnus Axelson, Jan Sjovall, Kjell WikvallAbstract:Pig liver microsomes were found to catalyze the 7α-hydroxylation of several potential bile acid precursors besides cholesterol. 26-Hydroxycholesterol, 3β-hydroxy-5-cholestenoic acid and 3β-hydroxy-5-cholenoic acid were all efficiently converted into the 7α-hydroxylated products. Two cytochrome P-450 fractions showing 7α-hydroxylase activity could be isolated. One fraction catalyzed 7α-hydroxylation of 26-Hydroxycholesterol. 3β-hydroxy-5-cholestenoic acid and 3β-hydroxy-5-cholenoic acid but was inactive towards cholesterol. The other fraction catalyzed 7α-hydroxylation of cholesterol in addition to the other substrates. 26-Hydroxycholesterol in equimolar concentration did not inhibit the cholesterol 7α-hydroxylase activity of this fraction. It is concluded that liver microsomes contain a cytochrome P-450 catalyzing 7α-hydroxylation of 26-Hydroxycholesterol, 3β-hydroxy-5-cholestenoic acid and 3β-hydroxy-5-cholenoic acid. The results indicate that this cytochrome P-450 is different from that catalyzing 7α-hydroxylation of cholesterol.
