Dataset Information


Deletion of TIPARP increases sensitivity to dioxin-induced hepatosteatosis and lethality

ABSTRACT: 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. 12 samples were analyzed. There were 4 treatment groups and each treatment group was done in triplicate. Gene expression changes were determine in hepatic RNA isolated from (1) corn oil treated C57BL/6;129Sv mice; (2) 30 ug/kg/bw 2,3,7,8-Tetrachlorodibenzo-p-dioxin C57BL/6;129Sv mice; (3) corn oil treated C57BL/6;129Sv Tiparp-/- mice; and (4) 30 ug/kg/bw 2,3,7,8-Tetrachlorodibenzo-p-dioxin C57BL/6;129Sv Tiparp-/- mice

ORGANISM(S): Mus musculus  

SUBMITTER: Jason Matthews   Debbie Bott  Yang Yang  Shaimaa Ahmed 

PROVIDER: E-GEOD-61534 | ArrayExpress | 2015-05-14



Similar Datasets

2009-11-24 | GSE10083 | GEO
2009-12-02 | E-GEOD-10083 | ArrayExpress
2011-11-14 | E-GEOD-13513 | ArrayExpress
2014-12-23 | E-GEOD-61039 | ArrayExpress
2018-10-31 | GSE122001 | GEO
2007-08-15 | GSE8468 | GEO
2007-08-14 | E-GEOD-8468 | ArrayExpress
2011-11-14 | GSE13513 | GEO
2016-07-03 | E-GEOD-72270 | ArrayExpress
2018-10-31 | GSE122002 | GEO