Abstract
A strain of hyperlipidaemic Sprague-Dawley (HSD) rat was compared with normal Sprague-Dawley (SD) rats for expression of cholesterol 7α-hydroxylase activity (CYP7A1) and other cytochrome P450 (P450) enzymes in liver. Hepatic microsomal CYP7A1 activity in male HSD rats was 2-3-fold lower than in male SD rats with CYP7A1 apoprotein levels being similarly reduced. CYP7A1 expression was subject to diurnal variation in HSD rats as found in SD rats. Treatment of HSD rats with cholestyramine caused an increase in hepatic microsomal cholesterol 7α-hydroxylase activity of 3.3-fold compared with a 3.5-fold increase in SD rats with similar changes in apoprotein levels. These results indicate that the lower activity in HSD rats is not due to a defect in the catalytic activity of the enzyme, regulation affecting diurnal variation or regulation through bile acid feedback inhibition. No difference between hepatic microsomal methoxyresorufin-O-demethylase, benzoxyresorufin-O-debenzylase or chlorzoxazone 6-hydroxylase activities in SD and HSD rats was found, nor was there any difference in the levels of CYP1A2, CYP2D1, CYP2E1, CYP3A1, CYP3A2 or NADPH cytochrome P450 reductase determined by immunoblotting using specific anti-peptide antibodies. However, unlike in male SD rats, CYP2C13 was absent in male HSD rats and this was associated with a two-fold reduction in testosterone 6β-hydroxylase activity. In conclusion, while HSD rats do not have a general reduction in P450 levels, they do lack CYP2C13 and have lowered cholesterol 7α-hydroxylase activity, as a result of a reduced level of expression of the enzyme. Copyright (C) 1998 Elsevier Science, Inc.
| Original language | English |
|---|---|
| Pages (from-to) | 253-257 |
| Number of pages | 5 |
| Journal | Biochemical Pharmacology |
| Volume | 56 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - Jul 15 1998 |
| Externally published | Yes |
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Keywords
- Cholesterol 7α-hydroxylase
- Cholestyramine
- CYP2C13
- CYP7A1
- Cytochrome P450
- Diurnal variation
- Spontaneously hyperlipidaemic rat
ASJC Scopus subject areas
- Pharmacology
Cite this
Reduced hepatic expression of CYP7A1 and CYP2C13 in rats with spontaneous hyperlipidaemia. / Brassil, Patrick J.; Debri, Khadija; Nakura, Hironori; Kobayashi, Shinichi; Davies, Donald S.; Edwards, Robert J.
In: Biochemical Pharmacology, Vol. 56, No. 2, 15.07.1998, p. 253-257.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Reduced hepatic expression of CYP7A1 and CYP2C13 in rats with spontaneous hyperlipidaemia
AU - Brassil, Patrick J.
AU - Debri, Khadija
AU - Nakura, Hironori
AU - Kobayashi, Shinichi
AU - Davies, Donald S.
AU - Edwards, Robert J.
PY - 1998/7/15
Y1 - 1998/7/15
N2 - A strain of hyperlipidaemic Sprague-Dawley (HSD) rat was compared with normal Sprague-Dawley (SD) rats for expression of cholesterol 7α-hydroxylase activity (CYP7A1) and other cytochrome P450 (P450) enzymes in liver. Hepatic microsomal CYP7A1 activity in male HSD rats was 2-3-fold lower than in male SD rats with CYP7A1 apoprotein levels being similarly reduced. CYP7A1 expression was subject to diurnal variation in HSD rats as found in SD rats. Treatment of HSD rats with cholestyramine caused an increase in hepatic microsomal cholesterol 7α-hydroxylase activity of 3.3-fold compared with a 3.5-fold increase in SD rats with similar changes in apoprotein levels. These results indicate that the lower activity in HSD rats is not due to a defect in the catalytic activity of the enzyme, regulation affecting diurnal variation or regulation through bile acid feedback inhibition. No difference between hepatic microsomal methoxyresorufin-O-demethylase, benzoxyresorufin-O-debenzylase or chlorzoxazone 6-hydroxylase activities in SD and HSD rats was found, nor was there any difference in the levels of CYP1A2, CYP2D1, CYP2E1, CYP3A1, CYP3A2 or NADPH cytochrome P450 reductase determined by immunoblotting using specific anti-peptide antibodies. However, unlike in male SD rats, CYP2C13 was absent in male HSD rats and this was associated with a two-fold reduction in testosterone 6β-hydroxylase activity. In conclusion, while HSD rats do not have a general reduction in P450 levels, they do lack CYP2C13 and have lowered cholesterol 7α-hydroxylase activity, as a result of a reduced level of expression of the enzyme. Copyright (C) 1998 Elsevier Science, Inc.
AB - A strain of hyperlipidaemic Sprague-Dawley (HSD) rat was compared with normal Sprague-Dawley (SD) rats for expression of cholesterol 7α-hydroxylase activity (CYP7A1) and other cytochrome P450 (P450) enzymes in liver. Hepatic microsomal CYP7A1 activity in male HSD rats was 2-3-fold lower than in male SD rats with CYP7A1 apoprotein levels being similarly reduced. CYP7A1 expression was subject to diurnal variation in HSD rats as found in SD rats. Treatment of HSD rats with cholestyramine caused an increase in hepatic microsomal cholesterol 7α-hydroxylase activity of 3.3-fold compared with a 3.5-fold increase in SD rats with similar changes in apoprotein levels. These results indicate that the lower activity in HSD rats is not due to a defect in the catalytic activity of the enzyme, regulation affecting diurnal variation or regulation through bile acid feedback inhibition. No difference between hepatic microsomal methoxyresorufin-O-demethylase, benzoxyresorufin-O-debenzylase or chlorzoxazone 6-hydroxylase activities in SD and HSD rats was found, nor was there any difference in the levels of CYP1A2, CYP2D1, CYP2E1, CYP3A1, CYP3A2 or NADPH cytochrome P450 reductase determined by immunoblotting using specific anti-peptide antibodies. However, unlike in male SD rats, CYP2C13 was absent in male HSD rats and this was associated with a two-fold reduction in testosterone 6β-hydroxylase activity. In conclusion, while HSD rats do not have a general reduction in P450 levels, they do lack CYP2C13 and have lowered cholesterol 7α-hydroxylase activity, as a result of a reduced level of expression of the enzyme. Copyright (C) 1998 Elsevier Science, Inc.
KW - Cholesterol 7α-hydroxylase
KW - Cholestyramine
KW - CYP2C13
KW - CYP7A1
KW - Cytochrome P450
KW - Diurnal variation
KW - Spontaneously hyperlipidaemic rat
UR - http://www.scopus.com/inward/record.url?scp=0031726261&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0031726261&partnerID=8YFLogxK
U2 - 10.1016/S0006-2952(98)00015-X
DO - 10.1016/S0006-2952(98)00015-X
M3 - Article
VL - 56
SP - 253
EP - 257
JO - Biochemical Pharmacology
JF - Biochemical Pharmacology
SN - 0006-2952
IS - 2
ER -