Changes of aryl hydrocarbon receptor in cardiac hypertrophy induced by high glucose in vitro

AIM: To investigate the changes of aryl hydrocarbon receptor (AhR) in the process of cardiomyocyte hypertrophy induced by high glucose, and to explore its potential mechanisms. METHODS: The rat cardiomyocytes (H9c2 cells) were divided into normal glucose group, high glucose group, DMSO group and resveratrol (an AhR antagonist) group. The content and distribution of AhR were observed with immunofluorescence staining. The myocardial cells were stained with rhodamine-labeled phalloidin to visualize cytoskeleton, and the cell surface area were determined after imaging by fluorescence microscopy. The generation of reactive oxygen species (ROS) in the cardiomyocytes was measured using a fluorescent probe DCFH-DA. The mRNA expression of AhR, CYP1A1, atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) were evaluated by real-time quantitative PCR (RT-qPCR). The protein levels of AhR, CYP1A1, ANP and BNP were assessed by Western blot. RESULTS: AhR was constitutively presented in the cytosol under normal-glucose condition and was translocated to the nuclei under high-glucose condition. High glucose induced cardiac hypertrophy, and increased ROS generation. Significant reductions in the cell size and ROS generation were observed after treated with resveratrol. The expression of AhR, CYP1A1, ANP and BNP at mRNA and protein levels in high glucose group was increased as compared with normal glucose group and resveratrol group, and the above-mentioned indexes significantly decreased in resveratrol group as compared with DMSO group. CONCLUSION: High glucose-induced cardiac hypertrophy increases AhR expression, which may be involved in the maintenance of glucose homeostasis in the cardiomyocytes. AhR translocation to the nucleus induced by high glucose results in the increases in CYP1A1 expression and ROS generation, which may be an important mechanism of high glucose-induced cardiomyocyte hypertrophy.