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首页> 外文期刊>Environmental Science & Technology >Xenobiotics Targeting Cardiolipin Metabolism to Promote Thrombosis in Zebrafish
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Xenobiotics Targeting Cardiolipin Metabolism to Promote Thrombosis in Zebrafish

机译:患有心肌脂肪蛋白代谢的Xenobiotics促进斑马鱼血栓形成

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摘要

Exposure to environmental pollutants is an important factor contributing to the development and severity of thrombosis. However, the important physiological molecules in the thrombotic processes affected by environmental exposures remain unknown. In this study, we show that exposure to environmental chemicals disrupts the equilibrium of cardiolipins (CLs), and directing CL synthesis promotes thrombosis. Using an untargeted metabolomics approach, approximately 3030 molecules were detected in zebrafish embryos exposed to 11 environmental chemicals and automatically clustered into a network. Interconnectivity among CLs and linoleates or isoxanthopterin was discovered through the highly consistent variations in the coregulated metabolites in the network. The chemical exposure resulted in significant upregulation of CLs through influencing the enzymatic activities of phospholipase A_2, cardiolipin synthase, and lysocardiolipin acyltransferase. Consequently, metabolic disorders of CLs affected the levels of anticardiolipin antibodies, disrupted the homeostasis between platelet thromboxane A_2 and endothelial prostacyclin, and promoted thrombotic events including heart ischemia and tachycardia- Our study thus reveals the common molecular mechanisms underlying the CL-induced thrombosis targeted by environmental exposures.
机译:暴露于环境污染物是有助于血栓形成的发展和严重程度的重要因素。然而,受环境暴露影响的血栓形成过程中的重要生理分子仍然未知。在这项研究中,我们表明,暴露于环境化学品破坏了心脂素(CLS)的平衡,并指导Cl合成促进血栓形成。使用未标准的代谢组种方法,在暴露于11个环境化学品的斑马鱼胚胎中检测到大约3030分子,并自动聚集到网络中。通过在网络中的重铸代谢物中的高度一致的变化发现Cls和LinoLeates或异昔尼酸中的互连性。通过影响磷脂酶A_2,心肝脂合酶和溶酶体丙氨酸酰酰基转移酶的酶活性,得到了化学照相的显着上调了Cls。因此,Cls的代谢紊乱影响了抗真生素抗体的水平,破坏了血小板血栓乳蛋白A_2和内皮前列腺内环素之间的稳态,并促进了包括心脏缺血和心动过速的血栓形成事件 - 我们的研究揭示了所针对的Cl诱导血栓形成的常见分子机制环境暴露。

著录项

  • 来源
    《Environmental Science & Technology》 |2021年第6期|3855-3866|共12页
  • 作者单位

    Laboratory for Earth Surface Processes College of Urban and Environmental Sciences Peking University Beijing 100871 China;

    Laboratory for Earth Surface Processes College of Urban and Environmental Sciences Peking University Beijing 100871 China;

    Laboratory for Earth Surface Processes College of Urban and Environmental Sciences Peking University Beijing 100871 China;

    Laboratory for Earth Surface Processes College of Urban and Environmental Sciences Peking University Beijing 100871 China;

    Laboratory for Earth Surface Processes College of Urban and Environmental Sciences Peking University Beijing 100871 China;

    Laboratory for Earth Surface Processes College of Urban and Environmental Sciences Peking University Beijing 100871 China;

    Laboratory for Earth Surface Processes College of Urban and Environmental Sciences Peking University Beijing 100871 China;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
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