Human sterol 12α-hydroxylase (CYP8B1) is mainly expressed in hepatocytes in a homogenous pattern

Wang, Jin; Greene, Sinead; Eriksson, Lennart C.; Rozell, Björn; Reihnér, Eva; Einarsson, Curt; Eggertsen, Gösta; Gåfvels, Mats

doi:10.1007/s00418-005-0779-0

Cited by 16 publications

(14 citation statements)

References 20 publications

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“…Thus, CYP8B1 activity determines the primary BA composition [73]. In human bile, CA and CDCA, representing two major primary BAs, occur in a molar ratio of ∼ 2 : 1 [74].…”

Section: Cyp8b1mentioning

confidence: 99%

“…Thus, CYP8B1 activity determines the primary BA composition [73]. In human bile, CA and CDCA, representing two major primary BAs, occur in a molar ratio of 2 : 1 [74]. The loss of activity of CYP8B1 leads to the production of CDCA over CA, which results in the modification of BA biosynthesis and changes in the excretion of cholesterol [75].…”

Section: Defects Of the Cyp8b1 Gene In Humansmentioning

confidence: 99%

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Cytochrome P450s in the synthesis of cholesterol and bile acids – from mouse models to human diseases

Lorbek¹,

Lewińska²,

2011

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The present review describes the transgenic mouse models that have been designed to evaluate the functions of the cytochrome P450s involved in cholesterol and bile acid synthesis, as well as their link with disease. The knockout of cholesterogenic Cyp51 is embrionally lethal, with symptoms of Antley–Bixler syndrome occurring in mice, whereas the evidence for this association is conflicting in humans. Disruption of Cyp7a1 from classic bile acid synthesis in mice leads to either increased postnatal death or a milder phenotype with elevated serum cholesterol. The latter is similar to the case in humans, where CYP7A1 mutations associate with high plasma low‐density lipoprotein and hepatic cholesterol content, as well as deficient bile acid excretion. Disruption of Cyp8b1 from an alternative bile acid pathway results in the absence of cholic acid and a reduced absorption of dietary lipids; however, the human CYP8B1 polymorphism fails to explain differences in bile acid composition. Unexpectedly, apparently normal Cyp27a1−/− mice still synthesize bile acids that originate from the compensatory pathway. In humans, CYP27A1 mutations cause cerebrotendinous xanthomatosis, suggesting that only mice can compensate for the loss of alternative bile acid synthesis. In line with this, Cyp7b1 knockouts are also apparently normal, whereas human CYP7B1 mutations lead to a congenital bile acid synthesis defect in children or spastic paraplegia in adults. Mouse knockouts of the brain‐specific Cyp46a1 have reduced brain cholesterol excretion, whereas, in humans, CYP46A1 polymorphisms associate with cognitive impairment. At present, cytochrome P450 family 39 is poorly characterized. Despite important physiological differences between humans and mice, mouse models prove to be an invaluable tool for understanding the multifactorial facets of cholesterol and bile acid‐related disorders.

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“…Thus, CYP8B1 activity determines the primary BA composition [73]. In human bile, CA and CDCA, representing two major primary BAs, occur in a molar ratio of ∼ 2 : 1 [74].…”

Section: Cyp8b1mentioning

confidence: 99%

Section: Defects Of the Cyp8b1 Gene In Humansmentioning

confidence: 99%

Cytochrome P450s in the synthesis of cholesterol and bile acids – from mouse models to human diseases

Lorbek¹,

Lewińska²,

2011

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“…In contrast, hydrophobic bile acids have been implicated in ER stress-induced apoptosis 33 . In relation to this, we found CYP8b1 to be highly expressed in GD cells compared to GC cells, unlike in normal liver, where it is diffusely expressed 34 CYP8b1 catalyzes sterol hydroxylation, which in turn determines the ratio of primary bile acids and solubility 35 Whether such changes would affect the solubility of polymerized ATZ protein is not yet known, and our attempts to compare bile acid composition in BDL versus sham-operated PiZZ mice were unsuccessful due to techinical issues.…”

Section: Discussionmentioning

confidence: 99%

Bile Duct Ligation Induces ATZ Globule Clearance in a Mouse Model of α-1 Antitrypsin Deficiency

Khan

Yokota²,

Bell³

et al. 2017

gene expr

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Background Alpha-1 antitrypsin deficiency (A1ATD) can progress to cirrhosis and hepatocellular carcinoma; however, not all patients are susceptible to severe liver disease. In A1ATD, a toxic gain-of-function mutation generates insoluble ATZ “globules” in hepatocytes, overwhelming protein clearance mechanisms. The relationship between bile acids and hepatocytic autophagy is less clear, but may involve altered gene expression pathways. Based on previous findings that bile duct ligation (BDL) induces autophagy, we hypothesized that retained bile acids may have hepatoprotective effects in PiZZ transgenic mice, which model A1ATD. Methods We performed BDL and partial BDL (pBDL) in PiZZ mice, followed by analysis of liver tissues. Results PiZZ liver subjected to BDL showed up to 50% clearance of ATZ globules, with increased expression of autophagy proteins. Analysis of transcription factors revealed significant changes. Surprisingly nuclear TFEB, a master regulator of autophagy, remained unchanged. pBDL confirmed that ATZ globule clearance was induced by localized stimuli rather than diet or systemic effects. Several genes involved in bile metabolism were over-expressed in globule-devoid hepatocytes, compared to globule-containing cells. Conclusions Retained bile acids led to a dramatic reduction of ATZ globules, with enhanced hepatocyte regeneration and autophagy. These findings support investigation of synthetic bile acids as potential autophagy-enhancing agents.

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“…In the context of chylomicrons, the work of Wang et al (2005) on hepatic synthesis of bile acids has to be mentioned. The sterol 12 -hydroxylase (CYP8B1) is a key enzyme in bile acid synthesis and was studied immunohistochemically.…”

Section: Histochemical Techniques In the Investigation Of Diseases Anmentioning

confidence: 99%

The histochemistry and cell biology vade mecum: a review of 2005–2006

Taatjes

Zuber

Roth

2006

Histochem Cell Biol

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The procurement of new knowledge and understanding in the ever expanding discipline of cell biology continues to advance at a breakneck pace. The progress in discerning the physiology of cells and tissues in health and disease has been driven to a large extent by the continued development of new probes and imaging techniques. The recent introduction of semi-conductor quantum dots as stable, specific markers for both fluorescence light microscopy and electron microscopy, as well as a virtual treasure-trove of new fluorescent proteins, has in conjunction with newly introduced spectral imaging systems, opened vistas into the seemingly unlimited possibilities for experimental design. Although it oftentimes proves difficult to predict what the future will hold with respect to advances in disciplines such as cell biology and histochemistry, it is facile to look back on what has already occurred. In this spirit, this review will highlight some advancements made in these areas in the past 2 years.

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Human sterol 12α-hydroxylase (CYP8B1) is mainly expressed in hepatocytes in a homogenous pattern

Cited by 16 publications

References 20 publications

Cytochrome P450s in the synthesis of cholesterol and bile acids – from mouse models to human diseases

Cytochrome P450s in the synthesis of cholesterol and bile acids – from mouse models to human diseases

Bile Duct Ligation Induces ATZ Globule Clearance in a Mouse Model of α-1 Antitrypsin Deficiency

The histochemistry and cell biology vade mecum: a review of 2005–2006

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