Abstract
Cholesterol epoxide hydrolase (mCE) is a microsomal enzyme that hydrolyzes cholesterol-5,6-epoxides (CE) to cholestanetriol (CT). In the present study, hepatic mCE activity was measured in mice pretreated with several different xenobiotics known to induce a variety of hepatic drug-metabolizing enzymes. Only the phenoxyacetate hypolipidemics (clofibrate and ciprofibrate, included in the diet for 14 days) were found to increase hepatic mCE activity (1.8-fold increase). Clofibrate administration also increased rabbit hepatic (2.9-fold increase) and rat and rabbit renal mCE activity (1.5- and 2.3-fold increase respectively). On a subcellular level, mCE activities in rabbit nuclear and light mitochondrial fractions were increased (3.3- and 1.8-fold increase respectively), whereas activities in the cytosolic and heavy mitochondrial fractions were unchanged. In rabbits, clofibrate administration enhanced the hepatic microsomal hydrolysis of CE without increasing the hydrolysis of arene epoxides (benzopyrene-4,5-oxide) or fatty acid epoxides (methyl cis-9,10-epoxystearate). Increase of tissue mCE activity may significantly enhance tissue CT levels. In this light, it is worth noting similarities in the mechanisms of hypocholesterolemic action caused by cloflbrate or CT administration.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 3169-3175 |
| Number of pages | 7 |
| Journal | Biochemical Pharmacology |
| Volume | 37 |
| Issue number | 16 |
| DOIs | |
| State | Published - Aug 15 1988 |
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ASJC Scopus subject areas
- Pharmacology
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Increased cholesterol epoxide hydrolase activity in clofibrate-fed animals. / Finley, Brent L.; Hammock, Bruce D.
In: Biochemical Pharmacology, Vol. 37, No. 16, 15.08.1988, p. 3169-3175.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Increased cholesterol epoxide hydrolase activity in clofibrate-fed animals
AU - Finley, Brent L.
AU - Hammock, Bruce D.
PY - 1988/8/15
Y1 - 1988/8/15
N2 - Cholesterol epoxide hydrolase (mCE) is a microsomal enzyme that hydrolyzes cholesterol-5,6-epoxides (CE) to cholestanetriol (CT). In the present study, hepatic mCE activity was measured in mice pretreated with several different xenobiotics known to induce a variety of hepatic drug-metabolizing enzymes. Only the phenoxyacetate hypolipidemics (clofibrate and ciprofibrate, included in the diet for 14 days) were found to increase hepatic mCE activity (1.8-fold increase). Clofibrate administration also increased rabbit hepatic (2.9-fold increase) and rat and rabbit renal mCE activity (1.5- and 2.3-fold increase respectively). On a subcellular level, mCE activities in rabbit nuclear and light mitochondrial fractions were increased (3.3- and 1.8-fold increase respectively), whereas activities in the cytosolic and heavy mitochondrial fractions were unchanged. In rabbits, clofibrate administration enhanced the hepatic microsomal hydrolysis of CE without increasing the hydrolysis of arene epoxides (benzopyrene-4,5-oxide) or fatty acid epoxides (methyl cis-9,10-epoxystearate). Increase of tissue mCE activity may significantly enhance tissue CT levels. In this light, it is worth noting similarities in the mechanisms of hypocholesterolemic action caused by cloflbrate or CT administration.
AB - Cholesterol epoxide hydrolase (mCE) is a microsomal enzyme that hydrolyzes cholesterol-5,6-epoxides (CE) to cholestanetriol (CT). In the present study, hepatic mCE activity was measured in mice pretreated with several different xenobiotics known to induce a variety of hepatic drug-metabolizing enzymes. Only the phenoxyacetate hypolipidemics (clofibrate and ciprofibrate, included in the diet for 14 days) were found to increase hepatic mCE activity (1.8-fold increase). Clofibrate administration also increased rabbit hepatic (2.9-fold increase) and rat and rabbit renal mCE activity (1.5- and 2.3-fold increase respectively). On a subcellular level, mCE activities in rabbit nuclear and light mitochondrial fractions were increased (3.3- and 1.8-fold increase respectively), whereas activities in the cytosolic and heavy mitochondrial fractions were unchanged. In rabbits, clofibrate administration enhanced the hepatic microsomal hydrolysis of CE without increasing the hydrolysis of arene epoxides (benzopyrene-4,5-oxide) or fatty acid epoxides (methyl cis-9,10-epoxystearate). Increase of tissue mCE activity may significantly enhance tissue CT levels. In this light, it is worth noting similarities in the mechanisms of hypocholesterolemic action caused by cloflbrate or CT administration.
UR - http://www.scopus.com/inward/record.url?scp=0023780585&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0023780585&partnerID=8YFLogxK
U2 - 10.1016/0006-2952(88)90316-4
DO - 10.1016/0006-2952(88)90316-4
M3 - Article
C2 - 3401248
AN - SCOPUS:0023780585
VL - 37
SP - 3169
EP - 3175
JO - Biochemical Pharmacology
JF - Biochemical Pharmacology
SN - 0006-2952
IS - 16
ER -