Induction and Superinduction of 2,3, 7,8-Tetrachlorodibenzo-P-Dioxin-Inducible ioly(ADP-Ribose) Polymerase: Role of the Aryl Hydrocarbon Receptor/Aryl Hydrocarbon Receptor Nuclear Translocator Transcription Activation Domains and a Labile Transcriptio

Details

• Personal Author:
  Ma Q
• Description:
  The environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induces a novel poly(ADP-ribose) polymerase (TiPARP). In this study, the signaling pathway of the induction was analyzed. Induction of TiPARP by TCDD occurs in both hepa1c1c7 cells and C57 mouse liver. Induction is concentration and time dependent. Genetic analyses reveal that induction is abolished in aromatic hydrocarbon receptor (AhR)- or aromatic hydrocarbon receptor nuclear translocator (Arnt)-defective variants but restored upon reconstitution of the variant cells with cDNAs expressing functional AhR or Arnt. Moreover, induction is largely reduced in cells expressing a deletion mutant of AhR or Arnt lacking the transcription activation (TA) domain, thus implicating the TA activities of both AhR and Arnt in the induction. Inhibition of protein synthesis by cycloheximide enhances the induction of TiPARP in the presence of an AhR agonist. The superinduction is transcriptional and does not require pretreatment with TCDD. Finally, inhibition of the 26S proteasomes by MG132 superinduces TiPARP. These findings establish that induction of TiPARP by TCDD is mediated through an AhR and Arnt transcription activation-dependent signal transduction that is repressed by a labile factor through the ubiquitin-26S proteasome-mediated protein degradation. [Description provided by NIOSH]
• Subjects:
  Animals Dioxins Environmental Pollution Genetics Hydrocarbons Laboratories Occupational Health Polycyclic Aromatic Hydrocarbons Safety
• Keywords:
  Animal-studies Aromatic-hydrocarbons Environmental-contamination Genetic-factors Laboratory-animals Liver-tissue
• ISSN:
  0003-9861
• 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
• Pages in Document:
  309-316
• Volume:
  404
• Issue:
  2
• NIOSHTIC Number:
  nn:20022859
• Citation:
  Arch Biochem Biophys 2002 Aug; 404(2):309-316
• Email:
  qam1@cdc.gov
• CAS Registry Number:
  2,3,7,8-Tetrachlorodibenzo-p-dioxin (CAS RN 1746-01-6)
• Federal Fiscal Year:
  2002
• Peer Reviewed:
  True
• Source Full Name:
  Archives of Biochemistry and Biophysics
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:230a348d4d39cb8e7dcbc160e852bd00d45faf9f49d75365c28911d823a84fe383038f2899844560fe8c9f467e7548a5ea0e832521574def77ed969846c5e95f
• Download URL:
  https://stacks.cdc.gov/view/cdc/199490/cdc_199490_DS1.pdf
• File Type:
  [PDF - 405.02 KB ]