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SOFT file
| Title / Description |
Deletion of TIPARP increases sensitivity to dioxin-induced hepatosteatosis and lethality |
| Accession |
GSE61534
|
| Summary |
The aryl hydrocarbon receptor (AHR) is a ligand activated transcription factor that mediates the toxic effects of the environmental contaminant, dioxin (2,3,7,8-tetrachlorodibenzo-p-dioxin; TCDD). Dioxin causes a diverse range of toxic responses, including hepatic damage and lethal wasting syndrome; however, the mechanisms of dioxin-induced toxicity are still unknown. Here we show that the loss of TCDD-inducible poly(ADP-ribose) polymerase (TIPARP; ARTD14), an ADP-ribosyltransferase and AHR repressor, increases sensitivity to dioxin-induced toxicity and lethality. Tiparp-/- mice treated with a single injection of 100 mg/kg dioxin display an accelerated lethal wasting syndrome with no Tiparp-/- mice surviving beyond day 5; all Tiparp+/+ mice survived up to 30 days post treatment. Tiparp-/- mice displayed dramatic increases in liver steatosis and hepatotoxicity. At the molecular level, TIPARP selectively ADP-ribosylates AHR, but not AHR nuclear translocator (ARNT) and the Tiparp-dependent repression of AHR is reversed by the ADP-ribosylase and macrodomain containing protein MacroD1, but not MacroD2. These results describe previously unidentified roles for Tiparp, MacroD1, and ADP-ribosylation in AHR signaling, dioxin toxicity and lethality. |
| Organism |
Mus musculus |
| Platform |
GPL6096 |
| Normalized |
False |
| Parsed SOFT file |
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Metadata
| Differential expression method |
Characteristic Direction
|
| Cutoff |
500 |
| Drug_name |
Tetradioxin |
| Smiles |
C1=C2C(=CC(=C1Cl)Cl)OC3=CC(=C(C=C3O2)Cl)Cl |
| Pubchem_cid |
15625 |
| Cell_type |
Liver ( Tiparp knockout ) - 8 weeks |
| Organism |
mouse |
Visualizations
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External Links and Downloads
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Gene lists
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Enrichr
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L1000CDS2
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PAEA
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