Regulation of TCDD-Induced Degradation of Ah Receptor by Cycloheximide

Details

• Personal Author:
  Antonini JM ; Baldwin KT ; Ma Q ; Renzelli AJ
• Description:
  2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) represents the prototype for a class of structurally related halogenated aromatic hydrocarbons (HAHs), including polychlorinated dibenzo-p-dioxins, dibenzofurans, and biphenyls 1,2 . Animals exposed to TCDD exhibit a wide range of toxic and adaptive responses, including a wasting syndrome, tumor promotion in skin and liver, cleft palate, chloracne, immune and endocrine dysfunctions, and induction of drug metabolizing enzymes 1-6. The health effect of TCDD on human beings remains a matter of debate. The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor with a basic helix-loop-helix PAS (bHLH/PAS) modular structure 2,3,7,8. Mouse genetic studies implicate AhR in most of the biological responses to TCDD, presumably by affecting the expression of target genes 9-11. Studies on the induction of CYP1A1 gene expression by TCDD provided major mechanistic understanding of the mechanism of action and regulation of AhR 2,3. In uninduced cells, AhR is localized in the cytoplasm, complexed with hsp90 12 and AIP, an immunophiltin-type chaperon protein 13-15. Binding with an agonist triggers the dissociation of AhR from the associated proteins and translocation into nucleus, where AhR dimerizes with Arnt, another bHLHPAS transcription factor 16. The AhR/Arnt dimer binds to a specific nucleotide sequence termed DRE (dioxin responsive element) in the enhancer region of the CYP1A1 gene 17; the transcription activation domains of AhR are essential for the subsequent transcriptional events, including alterations in chromatin structure, binding of general transcription factors to the promoter, and induction of transcription of the gene 2,3. [Description provided by NIOSH]
• Subjects:
  Animals Hydrocarbons Immune System Laboratories Neoplasms Occupational Health Safety
• Keywords:
  Animal Studies Aromatic Hydrocarbons Endocrine System Disorders Halogenated Compounds Halogenated Hydrocarbons Immune System Disorders Laboratory Animals Liver Tumors Skin Tumors Toxic Effects Tumors

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• ISBN:
  9780970331540
• Publisher:
  University of California, Davis
• Document Type:
  Text
• Genre:
  Proceedings
• Place as Subject:
  California ; OSHA Region 3 ; OSHA Region 9 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  318-321
• Volume:
  49
• NIOSHTIC Number:
  nn:20020998
• Citation:
  Organohalogen Compounds. Dioxin 2000: 20th International Symposium on Halogenated Environmental Organic Pollutants and Persistent Organic Pollutants (POPs), Monterey, California, USA, August 13-17, 2000. Volume 49: Toxicology; Non-Ah Receptor Mechanisms Underlying Immunotoxicity and Neurotoxicity of non-Coplanar-PCBs, PBDEs and Orthoquinones; Molecular Biology of the Ah Receptor and Ah Receptor-Dependent Signaling; Immunotoxicity of Dioxins and POPs; Endocrine Disruption; Ecotoxicology and POPs. Denison MS, ed., Davis, CA: University of California, Davis, 2000 Aug; 49:318-321
• CAS Registry Number:
  (-)-Cycloheximide (CAS RN 66-81-9) ; 2,3,7,8-Tetrachlorodibenzo-p-dioxin (CAS RN 1746-01-6)
• Editor(s):
  Denison MS
• Federal Fiscal Year:
  2000
• Peer Reviewed:
  False
• Source Full Name:
  Organohalogen Compounds. Dioxin 2000: 20th International Symposium on Halogenated Environmental Organic Pollutants and Persistent Organic Pollutants (POPs), Monterey, California, USA, August 13-17, 2000. Volume 49: Toxicology; Non-Ah Receptor Mechanisms Underlying Immunotoxicity and Neurotoxicity of non-Coplanar-PCBs, PBDEs and Orthoquinones; Molecular Biology of the Ah Receptor and Ah Receptor-Dependent Signaling; Immunotoxicity of Dioxins and POPs; Endocrine Disruption; Ecotoxicology and POPs
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:243fdb0620d35b9e4698873b22e97a40a7baea50da70892c2f6a63bc1a3f9ec2762883fe20bb1f06c7f165cc4d75d20a6c380f793c611c03367241b108e76dce
• Download URL:
  https://stacks.cdc.gov/view/cdc/198598/cdc_198598_DS1.pdf
• File Type:
  [PDF - 186.21 KB ]