Xenobiotic-Activated Receptors: From Transcription to Drug Metabolism to Disease

Details

• Personal Author:
  Ma Q
• Description:
  Xenobiotic-activated receptors (XARs) are a group of ligand-activated transcription factors that are evolutionally specialized to regulate genomic programs to protect the body against innumerable chemicals from the environment. XARs share unique properties, such as promiscuous ligand binding, conserved structural motifs, common protein partners, and overlapping target genes. These unique features of XARs clearly distinguish them from receptors that are activated by endogenous chemicals to regulate energy metabolism, reproduction, and growth and differentiation. XARs regulate xenobiotic metabolism and disposition by controlling the expression and induction of drug-metabolizing enzymes and transporters. Furthermore, XARs integrate a broad range of protective mechanisms, such as antioxidative response and immune/inflammatory functions, to antagonize foreign chemicals. As the primary means of xenobiotic sensing and defense, XARs are intimately involved in drug disposition, polymorphic drug clearance, drug-drug interaction, and pathogenesis of some chemically induced cancers and chronic diseases. As a consequence, some XAR characteristics have been exploited in drug development and safety evaluation of drugs and environmental carcinogens and toxicants. In this perspective, common features and recent advances in the structures, modes of action, and implications in disease and drug development of XARs are discussed. [Description provided by NIOSH]
• Subjects:
  Chemistry Genetics Hypersensitivity Immune System Occupational Health Safety
• Keywords:
  Cell-biology Cell-damage Cellular-reactions Chemical-analysis Chemical-binding Chemical-hypersensitivity Chemical-reactions Chemical-synthesis Chemoreceptors Drug-interaction Drugs Genes Genetic-factors Genotoxic-effects Immune-reaction Immune-system Immunochemistry

  More +
• ISSN:
  0893-228X
• 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:
  21
• Issue:
  9
• NIOSHTIC Number:
  nn:20034500
• Citation:
  Chem Res Toxicol 2008 Sep; 21(9):1651-1671
• Contact Point Address:
  Qiang Ma, NIOSH, 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, Morgantown, West Virginia 26505
• Email:
  qaml@cdc.gov
• Federal Fiscal Year:
  2008
• Peer Reviewed:
  True
• Source Full Name:
  Chemical Research in Toxicology
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:deae3b5e3d083be444da4e476ba84d21cb15c7fdde1ec92bbb1f4ae2104e349599f7dd1a59b622baf3f73bda047c3fb54a79b8fe9756a481620bb372175955df
• Download URL:
  https://stacks.cdc.gov/view/cdc/186724/cdc_186724_DS1.pdf
• File Type:
  [PDF - 1.99 MB ]