Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

0

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 

PROVIDER: E-GEOD-61534 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

Similar Datasets

2015-05-14 | GSE61534 | GEO
2009-12-02 | E-GEOD-10083 | biostudies-arrayexpress
2019-10-29 | GSE127217 | GEO
2009-06-24 | GSE16670 | GEO
2009-11-24 | GSE10083 | GEO
2011-11-14 | E-GEOD-13513 | biostudies-arrayexpress
2014-12-23 | E-GEOD-61039 | biostudies-arrayexpress
2019-06-01 | GSE114552 | GEO
2016-06-06 | GSE82242 | GEO
2007-08-14 | E-GEOD-8468 | biostudies-arrayexpress