NAD⁺ loss, a new player in AhR biology: prevention of thymus atrophy and hepatosteatosis by NAD⁺ repletion.

ABSTRACT: Dioxin (2,3,7,8-tetrachlorodibenzo-p-dioxin, TCDD) is a carcinogenic and highly toxic industrial byproduct that persists in the environment and produces a pleiotropic toxicity syndrome across vertebrate species that includes wasting, hepatosteatosis, and thymus atrophy. Dioxin toxicities require binding and activation of the aryl hydrocarbon receptor (AhR), a ligand activated transcription factor. However, after nearly 50 years of study, it remains unknown how AhR activation by dioxin produces toxic effects. Here, using the chick embryo close to hatching, a well-accepted model for dioxin toxicity, we identify NAD⁺ loss through PARP activation as a novel unifying mechanism for diverse effects of dioxin in vivo. We show that NAD⁺ loss is attributable to increased PARP a

SUBMITTER: Diani-Moore S 

PROVIDER: S-EPMC5442136 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature