High impact information on CYP8B1

• Addition of GDCA and GCDCA (100 micromol/L) significantly decreased sterol 12alpha-hydroxylase (CYP8B1) mRNA levels to 48% +/- 5% and 61% +/- 4% of controls, respectively, whereas GCA and GUDCA had no effect [1].
• Differential effects of sterol regulatory binding proteins 1 and 2 on sterol 12 alpha-hydroxylase. SREBP-2 suppresses the sterol 12 alpha-hydroxylase promoter [2].
• The sterol 12alpha-hydroxylase/CYP8B1 (12alpha-hydroxylase) promoter is also down-regulated by the C-36 peptide in HepG2 cells but not by the mutated peptide [3].
• Sterol 12 alpha-hydroxylase (12 alpha-hydroxylase) is required for cholic acid biosynthesis [2].
• A negative nuclear receptor, small heterodimer partner markedly inhibited transactivation of CYP8B1 by HNF4alpha [4].

Biological context of CYP8B1

• The human CYP8B1 promoter activities were strongly repressed by bile acids, and the bile acid response element was localized between +137 and +220 [4].
• To study the mechanism of CYP8B1 transcription by bile acids, we have cloned and determined 3389 base pairs of the 5'-upstream nucleotide sequences of the human CYP8B1 [4].
• The aim of this study was to investigate whether this marked difference could be due to a genetic polymorphism in the gene of the CYP8B1 [5].
• This hydroxylation is carried out by the sterol 12alpha-hydroxylase (CYP8B1) [5].
• Transcription of the mouse and human CYP8B1 genes was initiated from a position situated 51 and 35 bases, respectively, downstream of a consensus TATA box [6].

Anatomical context of CYP8B1

• CYP8B1 in human liver was expressed in the cytoplasm of hepatocytes with an even nonzonal distribution within the liver lobulus [7].

Associations of CYP8B1 with chemical compounds

• Transcriptional regulation of the human sterol 12alpha-hydroxylase gene (CYP8B1): roles of heaptocyte nuclear factor 4alpha in mediating bile acid repression [4].
• Transcription of CYP8B1 is inhibited by bile acids, cholesterol, and insulin [4].
• Sterol 12alpha-hydroxylase (CYP8B1) catalyzes cholic acid synthesis in the liver and is feedback inhibited by bile acids [8].
• Real-time PCR assays revealed that both chenodeoxycholic acid (CDCA) and interleukin-1beta (IL-1beta) markedly reduced CYP8B1, cholesterol 7alpha-hydroxylase CYP7A1 and hepatic nuclear factor 4alpha (HNF4alpha) mRNA expression levels in human primary hepatocytes [8].
• Cholesterol and 25-hydroxycholesterol decreased the CYP8B1/luciferase reporter activity [9].

Other interactions of CYP8B1

• Expression of mRNA levels of cholesterol 7alpha-hydroxylase (CYP7A1) and sterol 12alpha-hydroxylase (CYP8B1) dose-dependently decreased [10].
• Bile acids repress human CYP8B1 transcription by reducing the transactivation activity of HNF4alpha through interaction of HNF4alpha with SHP and reduction of HNF4alpha expression in the liver [4].
• The mRNA levels of CYP8B1, CYP27A1, and CYP7B1 were not significantly altered in the treated groups [11].
• Activated JNK1 or c-Jun inhibited, whereas their dominant negative forms blocked, IL-1beta inhibition of CYP8B1 transcription [8].
• These results suggest that IL-1beta inhibits CYP8B1 gene transcription via a mitogen-activated protein kinase/JNK pathway that inhibits HNF4alpha gene expression and its DNA-binding ability [8].

Analytical, diagnostic and therapeutic context of CYP8B1

• A specific anti-human CYP8B1 peptide antiserum was developed and used for Western blotting and hepatic immunostaining of livers from various patients [7].
• By using FISH and radiation hybrid mapping techniques, the human CYP8B1 gene was located to chromosome 3p21.3-p22, whereas FISH mapped the murine counterpart to chromosome 9qF4, a region that is homologous to the third human chromosome [6].
• Electrophoretic mobility shift assay and mutagenesis analyses identified several functional sterol regulatory elements (SRE) and E-box motifs in the rat CYP8B1 promoter [9].
• Thyroidectomy of rats caused a more than twofold increase of CYP8B1 and an almost fourfold increase of the corresponding mRNA levels compared to sham-operated rats [12].

References