Cardiac myocyte-specific AHR activation phenocopies TCDD-induced toxicity in zebrafish.

ABSTRACT: Exposure of zebrafish embryos to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) activates the zebrafish aryl hydrocarbon receptor 2 (AHR) to produce developmental and cardiovascular toxicity. AHR is found in the heart; however, AHR activation by TCDD is not confined to the heart and occurs throughout the organism. In order to understand the cause of cardiotoxicity, we constructed a constitutively active AHR (caAHR) based on the zebrafish AHR2 and expressed it specifically in cardiomyocytes. We show that AHR activation within the cardiomyocytes can account for the heart failure induced by TCDD. Expression of the caAHR within the heart produced cardiac malformations, loss of circulation, and pericardial edema. The heart-specific activation of AHR reproduced several other well-characterized endpo

SUBMITTER: Lanham KA 

PROVIDER: S-EPMC4271120 | biostudies-literature | 2014 Sep

REPOSITORIES: biostudies-literature