Stress response pathways protect germ cells from omega-6 polyunsaturated fatty acid-mediated toxicity in Caenorhabditis elegans.
Stress response pathways protect germ cells from omega-6 polyunsaturated fatty acid-mediated toxicity in Caenorhabditis elegans.
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DOI：
10.1016/j.ydbio.2012.10.002
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发表时间：
2013-01-01
影响因子：
2.7
通讯作者：
Watts JL
中科院分区：
文献类型：
--
作者：
Webster CM;Deline ML;Watts JL
多不饱和脂肪酸作为膜成分和涉及炎症和信号转导的许多不同因子的前体，具有结构和功能作用。这些脂肪酸是人类饮食中必需的，尽管膳食中过量摄入 omega-6 脂肪多不饱和脂肪酸可能会对人类健康产生负面影响。在线虫模型中，秀丽隐杆线虫从饮食中摄入二高γ-亚麻酸（DGLA）（一种 omega-6 脂肪酸）会导致生殖细胞遭到破坏并导致不育。在这项研究中，我们使用遗传和微观方法来进一步表征这种现象。我们发现，携带脂质稳态相关基因突变的菌株增强了不育表型，而降低保守胰岛素/IGF信号通路活性的突变则抑制了不育表型。在进行 omega-6 脂肪酸治疗之前暴露于轻度热应激会导致适应性或兴奋反应，从而导致不育率降低。 skn-1 突变和 II 相解毒酶编码基因敲低导致饮食中 DGLA 存在下不育性增加。因此，增加整体应激反应的解毒系统和遗传变化可以保护生殖细胞免受破坏。显微镜分析表明，饮食中的 DGLA 会导致发育中生殖系的增殖区和过渡区的生殖细胞膜恶化。总之，这些数据表明，特定的 omega-6 多不饱和脂肪酸或源自它们的分子被转运到生殖系，在那里它们破坏快速扩张的生殖细胞膜，导致生殖细胞死亡。
Polyunsaturated fatty acids serve both structural and functional roles as membrane components and precursors for a number of different factors involved in inflammation and signaling. These fatty acids are required in the human diet, although excess dietary intake of omega-6 fatty polyunsaturated fatty acids may have a negative influence on human health. In the model nematode, Caenorhabditis elegans, dietary exposure to dihomo- gamma-linolenic acid (DGLA), an omega-6 fatty acid, causes the destruction of germ cells and leads to sterility. In this study we used genetic and microscopic approaches to further characterize this phenomenon. We found that strains carrying mutations in genes involved in lipid homeostasis enhanced sterility phenotypes, while mutations reducing the activity of the conserved insulin/IGF signaling pathway suppressed sterility phenotypes. Exposure to a mild heat stress prior to omega-6 fatty acid treatment led to an adaptive or hormetic response, resulting in less sterility. Mutations in skn-1 and knockdown of genes encoding phase II detoxification enzymes led to increased sterility in the presence of dietary DGLA. Thus, detoxification systems and genetic changes that increase overall stress responses protect the germ cells from destruction. Microscopic analyses revealed that dietary DGLA leads to deterioration of germ cell membranes in the proliferative and transition zones of the developing germ line. Together, these data demonstrate that specific omega-6 polyunsaturated fatty acids, or molecules derived from them, are transported to the germ line where they disrupt the rapidly expanding germ cell membranes, leading to germ cell death.
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影响因子：
29
作者：
Greer, Elisabeth R.;Perez, Carissa L.;Van Gilst, Marc R.;Lee, Brian H.;Ashrafi, Kaveh
通讯作者：
Ashrafi, Kaveh
秀丽隐杆线虫中不饱和脂肪酸组成的遗传调节。
影响因子：
4.5
作者：
Brock, Trisha J.;Browse, John;Watts, Jennifer L.
通讯作者：
Watts, Jennifer L.
影响因子：
2.9
作者：
Funahashi, Hitoshi;Satake, Makoto;Eibl, Guido
通讯作者：
Eibl, Guido
DOI：
10.1086/650344
发表时间：
2010-02-01
期刊：
The Journal of infectious diseases
影响因子：
--
作者：
Bonilla DL;Fan YY;Chapkin RS;McMurray DN
通讯作者：
McMurray DN
影响因子：
5.3
作者：
Ferguson, Annabel A.;Springer, Mitchell G.;Fisher, Alfred L.
通讯作者：
Fisher, Alfred L.