CYP8B1
7-alpha-hydroxycholest-4-en-3-one 12-alpha-hydroxylase (EC 1.14.18.8) (7-alpha-hydroxy-4-cholesten-3-one 12-alpha-hydroxylase) (CYPVIIIB1) (Cytochrome P450 8B1) (Sterol 12-alpha-hydroxylase) [CYP12]
PublicationsПравить
n-3 PUFA such as EPA and DHA as well as oestrogen have been reported to decrease blood levels of cholesterol, but their underlying mechanism is unclear. The purpose of this study was to determine the effects of the combination of n-3 PUFA supplementation and oestrogen injection on hepatic cholesterol metabolism. Rats were fed a modified AIN-93G diet with 0, 1 or 2 % n-3 PUFA (EPA DHA) relative to the total energy intake for 12 weeks. Rats were surgically ovariectomised at week 8, and, after 1-week recovery, rats were injected with 17β-oestradiol-3-benzoate (E2) or maize oil for the last 3 weeks. Supplementation with n-3 PUFA and E2 injection significantly increased the ratio of the hepatic expression of phosphorylated AMP activated protein kinase (p-AMPK):AMP activated protein kinase (AMPK) and decreased sterol regulatory element-binding protein-2, 3-hydroxy-3-methylglutaryl coenzyme A reductase and proprotein convertase subtilisin/kexin type 9. Supplementation with n-3 PUFA increased hepatic expression of cholesterol 7α-hydroxylase (CYP7A1), sterol 12α-hydroxylase (CYP8B1) and sterol 27-hydroxylase (CYP27A1); however, E2 injection decreased CYP7A1 and CYP8B1 but not CYP27A1. Additionally, E2 injection increased hepatic expression of oestrogen receptor-α and β. In conclusion, n-3 PUFA supplementation and E2 injection had synergic hypocholesterolaemic effects by down-regulating hepatic cholesterol synthesis (n-3 PUFA and oestrogen) and up-regulating bile acid synthesis (n-3 PUFA) in ovariectomised rats.
MeSH Terms
- Aging
- Animals
- Anticholesteremic Agents
- Cholestanetriol 26-Monooxygenase
- Cholesterol 7-alpha-Hydroxylase
- Combined Modality Therapy
- Diet, Fat-Restricted
- Dietary Supplements
- Estradiol
- Estrogens
- Fatty Acids, Omega-3
- Female
- Hydroxymethylglutaryl CoA Reductases
- Hypercholesterolemia
- Liver
- Ovariectomy
- Proprotein Convertase 9
- Random Allocation
- Rats, Wistar
- Serine Endopeptidases
- Steroid 12-alpha-Hydroxylase
- Sterol Regulatory Element Binding Protein 2
Keywords
- n-3 PUFA
- AMPK AMP activated protein kinase
- CYP27A1 sterol 27-hydroxylase
- CYP7A1 cholesterol 7α-hydroxylase
- CYP8B1 sterol 12α-hydroxylase
- Cholesterol metabolism
- E2 17β-oestradiol-3-benzoate
- ER-α oestrogen receptor-α
- ER-β oestrogen receptor-β
- HMG-CoA reductase 3-hydroxy-3-methylglutaryl coenzyme A reductase
- Oestrogen
- Ovariectomised rats
- Proprotein convertase subtilisin/kexin type 9
- SREBP-2 sterol regulatory element-binding protein-2
- TC total cholesterol
- p-AMPK phosphorylated AMP activated protein kinase
The present review aims to give an overview of the cytochrome P450 8B (CYP8B) and cytochrome P450 4A (CYP4A) subfamilies in relation to biosynthesis of bile acids, in particular trihydroxy bile acids. Trihydroxy bile acids are basically required in most species and have an impact on cholesterol and lipid metabolism. The primary trihydroxy bile acid in most mammals is cholic acid. Some species produce other important trihydroxy bile acids, for example the adult pig which produce hyocholic acid instead of cholic acid. The position of the third hydroxyl group in cholic acid and hyocholic acid, 12alpha or 6alpha position, respectively, has a profound effect on the hydrophilic-hydrophobic property of the trihydroxy bile acids. The CYP8B subfamily is required for introduction of the 12alpha-hydroxyl group in cholic acid biosynthesis. The enzyme responsible for 6alpha-hydroxylation in hyocholic acid biosynthesis, however, varies among species. This review will discuss, in particular, porcine members of the CYP8B and CYP4A subfamilies because interesting findings regarding members of these subfamilies have recently been recognized in this species. CYP8B1 was for a long time believed to be absent in the pig but was recently found to be expressed in fetal pig liver. The enzyme catalyzing the 6alpha-hydroxylation in hyocholic acid biosynthesis in pig was found to be an atypical member of the CYP4A subfamily, denoted CYP4A21. The review presents bile acid biosynthesis in view of these findings and discusses physiochemical properties and developmental-dependent aspects related cholic acid and hyocholic acid biosynthesis.
MeSH Terms
- Aging
- Animals
- Bile
- Bile Acids and Salts
- Chemical Phenomena
- Chemistry, Physical
- Cytochrome P-450 CYP4A
- Humans
- Species Specificity
- Steroid Hydroxylases
- Swine