Activation of the aryl hydrocarbon receptor by doxorubicin mediates cytoprotective effects in the heart.

ABSTRACT:

Aims

Doxorubicin (DOX) is a highly effective chemotherapeutic agent; however, cumulative dose-dependent cardiotoxicity is a significant side effect of this therapy. Because DOX is a polyaromatic hydrocarbon, we hypothesized that it will be metabolized by the activation of the aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor that is involved in the metabolism of numerous xenobiotic agents. These studies were performed to determine whether DOX activates AhR and whether this activation modulates the toxicity of DOX in cardiomyocytes.

Methods and results

Treatment with DOX induced AhR migration to the nucleus, increased AhR binding with its co-factor, aryl hydrocarbon receptor nuclear translocator-1 (ARNT1), and increased the expression of AhR-regulated p

SUBMITTER: Volkova M 

PROVIDER: S-EPMC3078799 | biostudies-literature | 2011 May

REPOSITORIES: biostudies-literature