β-Catenin as a multilayer modulator of zonal cytochrome P450 expression in mouse liver

2010 ◽  
Vol 391 (2/3) ◽  
Author(s):  
Albert Braeuning ◽  
Michael Schwarz
Keyword(s):  
Cytochrome P450 ◽  
Mouse Liver ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Central Vein ◽  
Cytochrome P450 Enzymes ◽  
Metabolizing Enzymes ◽  
Major Organ ◽  
Exogenous Compounds ◽  
Review Current

Abstract The liver is the major organ for metabolism of drugs and other xenobiotics. Expression of many drug-metabolizing enzymes is not equally distributed throughout the liver: under normal conditions, many of them, including the most relevant members of the cytochrome P450 superfamily, are exclusively expressed in a hepatocyte subpopulation located near branches of the efferent central vein. Activation of different ligand-dependent transcription factors by exogenous compounds stimulates high expression of certain cytochrome P450 isoforms. This process also occurs preferentially in perivenous hepatocytes. The mechanisms, however, which determine the zone-specificity of basal and xenobiotic-induced expression of cytochrome P450 enzymes, have remained largely unknown for decades. Very recently, signaling through the Wnt/β-catenin pathway has been implicated in the regulation of zonal gene expression in mouse liver. In this review, current knowledge of cytochrome P450 regulation by β-catenin-dependent transcription is summarized and underlying molecular mechanisms are discussed.

The Toll-like receptor agonist imiquimod is metabolized by aryl hydrocarbon receptor-regulated cytochrome P450 enzymes in human keratinocytes and mouse liver

2019 ◽  
Vol 93 (7) ◽  
pp. 1917-1926 ◽  
Author(s):  
Melina Mescher ◽  
Julia Tigges ◽  
Katharina M. Rolfes ◽  
Anna L. Shen ◽  
Jeremiah S. Yee ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Aryl Hydrocarbon Receptor ◽  
Mouse Liver ◽  
Receptor Agonist ◽  
Human Keratinocytes ◽  
Toll Like Receptor ◽  
Cytochrome P450 Enzymes ◽  
Aryl Hydrocarbon

scholarly journals Molecular Basis of CYP19A1 Deficiency in a 46,XX Patient With R550W Mutation in POR: Expanding the PORD Phenotype

2020 ◽  
Vol 105 (4) ◽  
pp. e1272-e1290 ◽  
Author(s):  
Shaheena Parween ◽  
Mónica Fernández-Cancio ◽  
Sara Benito-Sanz ◽  
Núria Camats ◽  
Maria Natalia Rojas Velazquez ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Compound Heterozygous ◽  
Aromatase Activity ◽  
Cytochrome P450 Enzymes ◽  
Disorders Of Sexual Development ◽  
Illumina Platform ◽  
Metabolizing Enzymes ◽  
Cytochrome P450 Oxidoreductase ◽  
Deficiency Screening ◽  
Mtt Assays

Abstract Context Mutations in cytochrome P450 oxidoreductase (POR) cause a form of congenital adrenal hyperplasia (CAH). We report a novel R550W mutation in POR identified in a 46,XX patient with signs of aromatase deficiency. Objective Analysis of aromatase deficiency from the R550W mutation in POR. Design, setting, and patient Both the child and the mother had signs of virilization. Ultrasound revealed the presence of uterus and ovaries. No defects in CYP19A1 were found, but further analysis with a targeted Disorders of Sexual Development NGS panel (DSDSeq.V1, 111 genes) on a NextSeq (Illumina) platform in Madrid and Barcelona, Spain, revealed compound heterozygous mutations c.73_74delCT/p.L25FfsTer93 and c.1648C > T/p.R550W in POR. Wild-type and R550W POR were produced as recombinant proteins and tested with multiple cytochrome P450 enzymes at University Children’s Hospital, Bern, Switzerland. Main outcome measure and Results POR-R550W showed 41% of the WT activity in cytochrome c and 7.7% activity for reduction of MTT. Assays of CYP19A1 showed a severe loss of activity, and CYP17A1 as well as CYP21A2 activities were also lost by more than 95%. Loss of CYP2C9, CYP2C19, and CYP3A4 activities was observed for the R550W-POR. Predicted adverse effect on aromatase activity as well as a reduction in binding of NADPH was confirmed. Conclusions Pathological effects due to POR-R550W were identified, expanding the knowledge of molecular pathways associated with aromatase deficiency. Screening of the POR gene may provide a diagnosis in CAH without defects in genes for steroid metabolizing enzymes.

scholarly journals Acetaminophen-Induced Liver Injury Alters Expression and Activities of Cytochrome P450 Enzymes in an Age-Dependent Manner in Mouse Liver

2020 ◽  
Vol 48 (5) ◽  
pp. 326-336 ◽  
Author(s):  
Yifan Bao ◽  
Pei Wang ◽  
Xueyan Shao ◽  
Junjie Zhu ◽  
Jingcheng Xiao ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Liver Injury ◽  
Mouse Liver ◽  
Dependent Manner ◽  
Cytochrome P450 Enzymes ◽  
Age Dependent

P16 - Drug-induced liver injury alters expression and activities of drug-metabolizing cytochrome P450 enzymes in mouse liver at different ages

2020 ◽  
Vol 35 (1) ◽  
pp. S26-S27
Author(s):  
Yifan Bao ◽  
Xueyan Shao ◽  
Pei Wang ◽  
Junjie Zhu ◽  
Jingcheng Xiao ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Liver Injury ◽  
Mouse Liver ◽  
Cytochrome P450 Enzymes ◽  
Drug Induced ◽  
Drug Induced Liver Injury ◽  
Different Ages

Mechanisms of integration of cells and extracellular matrices by integrins

2004 ◽  
Vol 32 (5) ◽  
pp. 822-825 ◽  
Author(s):  
M.J. Humphries ◽  
M.A. Travis ◽  
K. Clark ◽  
A.P. Mould
Keyword(s):  
Cellular Differentiation ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Tissue Architecture ◽  
Integrin Receptors ◽  
Adhesion Receptor ◽  
Surface Receptors ◽  
Integrate Work ◽  
Extracellular Molecules ◽  
Review Current

While it is self-evident that all extracellular molecules are an integral part of a multicellular organism, it is paradoxical that they are often considered to be dissociated from cells. The reality is that a continuum of dynamic, bi-directional interactions links the intracellular environment through cell-surface receptors to multimolecular extracellular assemblies. These interactions not only control the behaviour of individual cells, but also determine tissue architecture. Adhesion receptor function is partly determined by an ability to tether the contractile cytoskeleton to the plasma membrane, but there is also evidence that integrin receptors modulate signalling events that are essential for cellular differentiation. A major challenge is now to integrate work at the atomic, molecular and cellular levels, and obtain holistic insights into the mechanisms controlling cell adhesion. In the present study, we review current knowledge of the molecular mechanisms employed by cells to integrate with the extracellular matrix. Two main topics are covered: the adaptation of integrin structure for bi-directional signalling and the integration of integrin signalling with other receptors.

scholarly journals Molecular Basis of CYP19A1 Deficiency in a 46, XX Patient with R550W Mutation in POR: Expanding the PORD Phenotype

2020 ◽  
Author(s):  
Shaheena Parween ◽  
Mónica Fernández-Cancio ◽  
Sara Benito-Sanz ◽  
Núria Camats ◽  
Maria Natalia Rojas Velazquez ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Compound Heterozygous ◽  
Aromatase Activity ◽  
Cytochrome P450 Enzymes ◽  
Disorders Of Sexual Development ◽  
Illumina Platform ◽  
Metabolizing Enzymes ◽  
Cytochrome P450 Oxidoreductase ◽  
Deficiency Screening ◽  
Mtt Assays

Context: Mutations in Cytochrome P450 oxidoreductase (POR) cause a form of congenital adrenal hyperplasia (CAH). We are reporting a novel R550W mutation in POR identified in a 46, XX patient with signs of aromatase deficiency. Objective: Analysis of aromatase deficiency from R550W mutation in POR. Design, Setting, and Patient: Both the child and the mother had signs of virilization. Ultrasound revealed the presence of uterus and ovaries. No defects in CYP19A1 were found, but further analysis with a targeted Disorders of Sexual Development NGS panel (DSDSeq.V1, 111 genes) on a NextSeq (Illumina) platform in Madrid and Barcelona, Spain, revealed compound heterozygous mutations c.73_74delCT/p.L25FfsTer93 and c.1648C>T/p.R550W in POR. WT and R550W POR were produced as recombinant proteins and tested with multiple cytochrome P450 enzymes at University Children’s Hospital, Bern, Switzerland. Main Outcome Measure and Results: R550W POR showed 41% of the WT activity in cytochrome c and 7.7% activity for reduction of MTT. Assays of CYP19A1 showed a severe loss of activity and CYP17A1, as well as CYP21A2 activities, were also lost by more than 95%. Loss of CYP2C9, CYP2C19, and CYP3A4 activities was observed for the R550W-POR. Predicted adverse effect on aromatase activity as well as a reduction in binding of NADPH was confirmed. Conclusions: Pathological effects due to POR R550W were identified, expanding the knowledge of molecular pathways associated with aromatase deficiency. Screening of the POR gene may provide a diagnosis in CAH without defects in genes for steroid metabolizing enzymes.

Molecular mechanisms controlling nutritive blood flow: role of cytochrome P450 enzymes

2000 ◽  
Vol 168 (4) ◽  
pp. 543-549 ◽  
Author(s):  
D.R. Harder ◽  
R. J. Roman ◽  
D. Gebremedhin
Keyword(s):  
Blood Flow ◽  
Cytochrome P450 ◽  
Molecular Mechanisms ◽  
Cytochrome P450 Enzymes

scholarly journals When fate follows age: unequal centrosomes in asymmetric cell division

2014 ◽  
Vol 369 (1650) ◽  
pp. 20130466 ◽  
Author(s):  
Jose Reina ◽  
Cayetano Gonzalez
Keyword(s):  
Stem Cells ◽  
Cell Division ◽  
Strong Correlation ◽  
Molecular Mechanisms ◽  
Asymmetric Cell Division ◽  
Current Knowledge ◽  
Cell Types ◽  
Functional Implications ◽  
Different Cell Types ◽  
Review Current

A strong correlation between centrosome age and fate has been reported in some stem cells and progenitors that divide asymmetrically. In some cases, such stereotyped centrosome behaviour is essential to endow stemness to only one of the two daughters, whereas in other cases causality is still uncertain. Here, we present the different cell types in which correlated centrosome age and fate has been documented, review current knowledge on the underlying molecular mechanisms and discuss possible functional implications of this process.

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