Phosphorylation of xenobiotic-metabolizing cytochromes P450.

2.50
Hdl Handle:
http://hdl.handle.net/10146/82633
Title:
Phosphorylation of xenobiotic-metabolizing cytochromes P450.
Authors:
Oesch-Bartlomowicz, B.; Oesch, F.
Abstract:
The regulation of cytochromes P450 (CYPs) by induction mediated by xenobiotics is well known. Our team has discovered an additional important regulation of xenobiotic-metabolizing CYPs by phosphorylation. Individual CYPs are phosphorylated by different protein kinases, leading to CYP isoenzyme-selective changes in the metabolism of individual substrates and consequent profound changes in the control of mutagenic and cytotoxic metabolites. Some CYPs are phosphorylated by protein kinase C and some by the cyclic adenosine monophosphate (cAMP) dependent protein kinase A. We found that cAMP not only leads to drastic changes in the activity of individual CYPs, but also drastic changes in the nuclear localization of the CYP-related transcription factor Ah receptor (AHR). The consequences are very different from those of AHR nuclear translocation mediated by its classic ligands (such as dioxin and many polycyclic aromatic hydrocarbons) and may represent the long-sought physiological function of the AHR. The disturbance of this physiological function of AHR by extremely persistent high-affinity xenobiotic ligands such as dioxin may represent the most important contributing factor for their potent toxicity.
Citation:
Anal. Bioanal. Chem. 2008, 392 (6):1085-1092
Journal:
Analytical and bioanalytical chemistry
Issue Date:
Nov-2008
URI:
http://hdl.handle.net/10146/82633
DOI:
10.1007/s00216-008-2315-2
PubMed ID:
18704375
Additional Links:
http://www.springerlink.com/content/1317418n45376145/
Type:
Article
Language:
en
ISSN:
1618-2650
Sponsors:
The authors thank the EU Network of Excellence ECNIS (Environmental Cancer, Nutrition and Individual Susceptibility) operating within the EU Sixth Framework Programme, Priority 5: “Food Quality and Safety” (contract no. 513943) for support.
Appears in Collections:
Articles

Full metadata record

DC FieldValue Language
dc.contributor.authorOesch-Bartlomowicz, B.en
dc.contributor.authorOesch, F.en
dc.date.accessioned2009-09-25T07:46:56Z-
dc.date.available2009-09-25T07:46:56Z-
dc.date.issued2008-11-
dc.identifier.citationAnal. Bioanal. Chem. 2008, 392 (6):1085-1092en
dc.identifier.issn1618-2650-
dc.identifier.pmid18704375-
dc.identifier.doi10.1007/s00216-008-2315-2-
dc.identifier.urihttp://hdl.handle.net/10146/82633-
dc.description.abstractThe regulation of cytochromes P450 (CYPs) by induction mediated by xenobiotics is well known. Our team has discovered an additional important regulation of xenobiotic-metabolizing CYPs by phosphorylation. Individual CYPs are phosphorylated by different protein kinases, leading to CYP isoenzyme-selective changes in the metabolism of individual substrates and consequent profound changes in the control of mutagenic and cytotoxic metabolites. Some CYPs are phosphorylated by protein kinase C and some by the cyclic adenosine monophosphate (cAMP) dependent protein kinase A. We found that cAMP not only leads to drastic changes in the activity of individual CYPs, but also drastic changes in the nuclear localization of the CYP-related transcription factor Ah receptor (AHR). The consequences are very different from those of AHR nuclear translocation mediated by its classic ligands (such as dioxin and many polycyclic aromatic hydrocarbons) and may represent the long-sought physiological function of the AHR. The disturbance of this physiological function of AHR by extremely persistent high-affinity xenobiotic ligands such as dioxin may represent the most important contributing factor for their potent toxicity.en
dc.description.sponsorshipThe authors thank the EU Network of Excellence ECNIS (Environmental Cancer, Nutrition and Individual Susceptibility) operating within the EU Sixth Framework Programme, Priority 5: “Food Quality and Safety” (contract no. 513943) for support.en
dc.language.isoenen
dc.relation.urlhttp://www.springerlink.com/content/1317418n45376145/en
dc.subjectCytochromes P450en
dc.subjectPhosphorylationen
dc.subjectProtein kinase Aen
dc.subjectcAMPen
dc.subjectDrug metabolismen
dc.subjectAh receptor nuclear translocationen
dc.subject.meshCyclic AMP-
dc.subject.meshCyclic AMP-Dependent Protein Kinases-
dc.subject.meshCytochrome P-450 Enzyme System-
dc.subject.meshDioxins-
dc.subject.meshLigands-
dc.subject.meshPhosphorylation-
dc.subject.meshPolycyclic Hydrocarbons, Aromatic-
dc.subject.meshProtein Kinase C-
dc.subject.meshReceptors, Aryl Hydrocarbon-
dc.subject.meshReceptors, Cytoplasmic and Nuclear-
dc.subject.meshXenobiotics-
dc.titlePhosphorylation of xenobiotic-metabolizing cytochromes P450.en
dc.typeArticleen
dc.identifier.journalAnalytical and bioanalytical chemistryen

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