2. Academic Validation
  3. Aryl hydrocarbon receptor mediates the cardiac developmental toxicity of EOM from PM2.5 in P19 embryonic carcinoma cells

Aryl hydrocarbon receptor mediates the cardiac developmental toxicity of EOM from PM2.5 in P19 embryonic carcinoma cells

  • Chemosphere. 2019 Feb;216:372-378. doi: 10.1016/j.chemosphere.2018.10.160.
Tao Chen 1,  Hongmei Jin 1,  Huimin Wang 1,  Yugang Yao 2,  Stanley Aniagu 3,  Jian Tong 1,  Yan Jiang 4
Affiliations

Affiliations

  • 1 Medical College of Soochow University, Suzhou, China; Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Soochow University, Suzhou, China.
  • 2 Suzhou Environmental Monitor Center, Key Laboratory of Atmospheric Combined Pollution Monitoring, Environmental Protection Department of Jiangsu Province, Suzhou, China.
  • 3 Toxicology Division, Texas Commission on Environmental Quality, Austin, TX, USA.
  • 4 Medical College of Soochow University, Suzhou, China. Electronic address: [email protected].
PMID: 30384306 DOI: 10.1016/j.chemosphere.2018.10.160
Abstract

Ambient fine particulate matter (PM2.5) has been found to be associated with congenital heart defects, but the molecular mechanisms remain to be elucidated. Our previous study revealed that extractable organic matter (EOM) from PM2.5 exerted cardiac developmental toxicity in zebrafish embryos. The aim of the current study is to explore the effects of EOM on cardiac differentiation of P19 mouse embryonic carcinoma stem cells. We found that EOM at 10 μg/ml (a non-cytotoxic dose level) significantly reduced the proportion of cardiac muscle troponin (cTnT) positive cells and the percentage of spontaneously beating embryoid bodies, indicating a severe inhibition of cardiac differentiation. Immunofluorescence and qPCR data demonstrated that EOM increased the expression levels of the Aryl Hydrocarbon Receptor (AhR) and its target gene Cyp1A1 and diminished the expression level of β-catenin. Furthermore, EOM treatment significantly upregulated cell proliferation rate and elevated the percentage of γH2A.X positive cells without affecting Apoptosis. It is worth noting that the EOM-induced changes in gene expression, cellular proliferation and DNA double strain breaks were attenuated by the AhR antagonist CH223191. In conclusion, our data indicate that AhR mediates the inhibitory effects of EOM (from PM2.5) on the cardiac differentiation of P19 cells.

Keywords

AhR; Cardiac differentiation; Cell proliferation; PM(2.5); γH2A.X.

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