title: Phenanthrene exposure produces cardiac defects during embryo development of zebrafish (Danio rerio) through activation of MMP-9.
abstract: Phenanthrene (Phe) is one of the most abundant polycyclic aromatic hydrocarbons in the aquatic environment as a result of human activities. It is widely accepted that Phe has cardiotoxic effects. Even so, knowledge concerning the mechanism(s) of cardiac development toxicity is still limited. In this study, we exposed zebrafish embryos to environmentally relevant concentrations of Phe and then investigated its cardiotoxic effects and the mechanism(s) involved. Some cardiac morphogenetic defects, which was characterized by an abnormally looped and enlarged heart, dilated and thinner ventricular wall, and increased interstitial fibrosis, were observed in the Phe treated groups. The mRNA and protein expression levels of matrix metalloproteinase-9 (MMP-9), as well as the MMP-9 activity, were induced. Moreover, during co-treatment of the zebrafish embryos with MMP-9 inhibitor, the cardiac defects caused by Phe were attenuated. In addition, Phe exposure led to an up-regulation of transforming growth factor β (TGF-β), which plays a crucial role in mediating cardiac fibrosis. Taken together, our data indicated that the exposure to Phe of zebrafish embryos disrupted normal cardiac development, and that the cardiac defects induced by Phe were mediated by the MMP-9, while TGF-β was also involved in these cardiac defects.
authors.affiliation: State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen 361005, China.
authors.forename: Youyu
authors.initials: Y
authors.lastname: Zhang
authors.forename: Lixing
authors.initials: L
authors.lastname: Huang
authors.forename: Chonggang
authors.initials: C
authors.lastname: Wang
authors.forename: Dongxu
authors.initials: D
authors.lastname: Gao
authors.forename: Zhenghong
authors.initials: Z
authors.lastname: Zuo
mesh_terms: D000014:Abnormalities, Drug-Induced / Q000378:metabolism*; D000818:Animals; D018376:Cardiovascular Abnormalities; D004625:Embryo, Nonmammalian / Q000187:drug effects*; D047108:Embryonic Development / Q000187:drug effects*; D018507:Gene Expression Regulation, Developmental; D006321:Heart / Q000187:drug effects* / Q000254:growth & development; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D010616:Phenanthrenes / Q000633:toxicity*; D015854:Up-Regulation; D014874:Water Pollutants, Chemical / Q000633:toxicity*; D015027:Zebrafish / Q000002:abnormalities* / Q000196:embryology
chemical_list: D010616:Phenanthrenes; D014874:Water Pollutants, Chemical; C031181:phenanthrene; D020780:Matrix Metalloproteinase 9
keywords: Cardiac defects; MMP-9; Phenanthrene; Zebrafish