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10.RegulationI

10.RegulationI - NS120 Molecular Toxicology Aryl...

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Aryl Hydrocarbon Receptor and Antioxidant Response NS120 Molecular Toxicology
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Learning Objectives z Describe what is meant by xenobiotic mediated gene induction. What are the targets of gene induction? z What are the evolutionary advantages of xenobiotic gene induction? z What are some of the causes of intra and inter individual variation? z Describe the mechanism of AHR mediated induction of CYP expression. z What is meant by a bifunctional inducer? z Describe some of the tools used to identify the receptors for known response elements.
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Readings Î ACTIVATION OF THE ARYL HYDROCARBON RECEPTOR BY STRUCTURALLY DIVERSE EXOGENOUS AND ENDOGENOUS CHEMICALS Annu. Rev. Pharmacol. Toxicol. 2003. 43:309–34 Î REGULATORYMECHANISMS CONTROLLING GENE EXPRESSION MEDIATED BY THE ANTIOXIDANT RESPONSE ELEMENT Annu. Rev. Pharmacol. Toxicol. 2003. 43:233–60 Î Chapter 5 of Mechanistic Toxicology by Urs A. Boelsterli, pp.93-135
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Xenobiotic receptors Î Aryl Hydrocarbon Receptor Î Nuclear Receptors - RXR Î Orphan Nuclear Receptors Í CAR Í PXR Í PPAR
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P450 Induction - Why? 1. Protective mechanism 2. Express as needed
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Evolutionary Development of Xenobiotic Metabolism As plants have developed more sophisticated chemical defenses, animals have developed more elaborate biochemical responses. Animal
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  • Spring '11
  • Vulpe
  • Cytochrome P450, Transcription factor, Aryl hydrocarbon receptor nuclear translocator, Aryl hydrocarbon receptor

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10.RegulationI - NS120 Molecular Toxicology Aryl...

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