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Issue Date
2008-11
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Show full item recordAbstract
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):1085-1092PubMed ID
18704375Additional Links
http://www.springerlink.com/content/1317418n45376145/Type
ArticleLanguage
enISSN
1618-2650Sponsors
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.ae974a485f413a2113503eed53cd6c53
10.1007/s00216-008-2315-2
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