Influence of light on aryl hydrocarbon receptor signaling and consequences in drug metabolism, physiology and disease

Details

• Personal Author:
  Ma Q
• Description:
  Introduction: A key to understanding the biological function(s) of the aryl hydrocarbon receptor (AHR) - a xenobiotic-activated receptor - is to identify its endogenous ligand(s). The discovery of a tryptophan photoproduct 6-formylindolo[3,2-b]carbazole (FICZ) as an endogenous, high affinity agonist of AHR filled this knowledge gap in the context of skin physiology and pathology in response to light and opened several new directions for research on AHR. Area covered: This paper reviews major developments in the study of light-elicited AHR signaling and its impact on drug metabolism, skin physiology and disease with a focus on the identification of AHR ligands from Trp photoproducts and the AHR-mediated UV response. This review consists of material obtained from Medline and PubMed literature searches up to May 2011. Expert opinion: The recognition of FICZ as a potent, endogenous ligand of AHR provided a molecular link between light exposure and AHR signaling and function. The uncovering of the bifurcated signaling pathway of AHR in the mammalian UV response - that is, activation of the cytoplasmic AHR by light via FICZ leads to: i) AHR/AH response element-dependent transcription to induce CYP1A1 and ii) activation of the AHR-pp60src-EGFR pathway to induce Cox-2 - put forward a working model for the multiple roles of AHR in skin function and disease that include drug metabolism, circadian oscillation, melanogenesis, inflammation, immunosuppression and cancer. Such findings suggest AHR as a therapeutic target for cancer, autoimmune dysfunction, inflammatory disease and stem cell therapy. [Description provided by NIOSH]
• Subjects:
  Chemistry Environmental Monitoring Hazardous Substances Neoplasms Occupational Health Particulate Matter Safety Workplace
• Keywords:
  AHR Ligand Author Keywords: AH Receptor Biohazards Biological-effects Biological-monitoring Biological-systems Cancer-rates Cell-function Cell-metabolism Cell-transformation Cellular-function Cellular-reactions Chemical-properties CYP1A1 Induction Exposure-assessment Fibrogenicity Fibrous-bodies FICZ Measurement-equipment Particle-aerodynamics Particulate-dust Particulates Tryptophan Photoreaction UV Response Work-areas Work-operations Worker-health

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• ISSN:
  1742-5255
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  OSHA Region 3 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  7
• Issue:
  10
• NIOSHTIC Number:
  nn:20039631
• Citation:
  Expert Opin Drug Metab Toxicol 2011 Oct; 7(10):1267-1293
• Contact Point Address:
  Qiang Ma Lead Toxicologist and Team Leader, Receptor Biology Laboratory, Toxicology and Molecular Biology Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, Mail
• Federal Fiscal Year:
  2012
• NORA Priority Area:
  Manufacturing
• Peer Reviewed:
  True
• Source Full Name:
  Expert Opinion on Drug Metabolism & Toxicology
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:511d6a929359b62dcb0cfb330e6f2b9fe619c8e5f837e97d5f1e26da60b42f2c92ef061df183ded429d526413f8708157b889341664aee72a298c7fd289ef915
• Download URL:
  https://stacks.cdc.gov/view/cdc/192804/cdc_192804_DS1.pdf
• File Type:
  [PDF - 807.60 KB ]