Atrazine binds to F1F0-ATP synthase and inhibits mitochondrial function in sperm.
Atrazine binds to F1F0-ATP synthase and inhibits mitochondrial function in sperm.
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DOI：
10.1016/j.bbrc.2007.11.107
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发表时间：
2008-02
影响因子：
3.1
通讯作者：
Y. Hase;M. Tatsuno;T. Nishi;K. Kataoka;Y. Kabe;Y. Yamaguchi;N. Ozawa;M. Natori;H. Handa;Hajime Watanabe
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文献类型：
--
作者：
Y. Hase;M. Tatsuno;T. Nishi;K. Kataoka;Y. Kabe;Y. Yamaguchi;N. Ozawa;M. Natori;H. Handa;Hajime Watanabe
阿特拉津是一种广泛使用的三嗪类除草剂。尽管仍存在争议，但最近的一些研究已经描述了其对包括人类在内的各种动物的不利影响。特别令人感兴趣的是它对生殖能力的影响。在这项研究中，我们研究了阿特拉津的不良反应的机制，重点是它对精子的影响。在这里，我们表明线粒体F1 F0-ATP合酶是阿特拉津的分子靶点的证据。一系列精子和分离线粒体的实验表明，阿特拉津通过F1 F0-ATP合酶抑制线粒体功能。此外，使用阿特拉津作为配体的亲和纯化表明，F1 F0-ATP合酶是细胞中的主要阿特拉津结合蛋白。对线粒体和F1 F0-ATP合酶的抑制活性不限于阿特拉津，而是可能适用于其它基于三嗪的化合物。因此，我们的研究结果可能与药理学和毒理学具有广泛的相关性。
Atrazine is a widely used triazine herbicide. Although controversy still exists, a number of recent studies have described its adverse effects on various animals including humans. Of particular interest is its effects on reproductive capacity. In this study, we investigated the mechanisms underlying the adverse effects of atrazine, with a focus on its effects on sperm. Here we show evidence that mitochondrial F1F0-ATP synthase is a molecular target of atrazine. A series of experiments with sperm and isolated mitochondria suggest that atrazine inhibits mitochondrial function through F1F0-ATP synthase. Moreover, affinity purification using atrazine as a ligand demonstrates that F1F0-ATP synthase is a major atrazine-binding protein in cells. The inhibitory activity against mitochondria and F1F0-ATP synthase is not limited to atrazine but is likely to be applicable to other triazine-based compounds. Thus, our findings may have wide relevance to pharmacology and toxicology.