The Metabolomic Responses of Caenorhabditis elegans to Cadmium Are Largely Independent of Metallothionein Status, but Dominated by Changes in Cystathionine and Phytochelatins
The Metabolomic Responses of Caenorhabditis elegans to Cadmium Are Largely Independent of Metallothionein Status, but Dominated by Changes in Cystathionine and Phytochelatins
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DOI：
10.1021/pr9001806
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发表时间：
2009-07-01
影响因子：
4.4
通讯作者：
Sturzenbaum, Stephen R.
中科院分区：
文献类型：
--
作者：
Hughes, Samantha L.;Bundy, Jacob G.;Sturzenbaum, Stephen R.
镉是一种广泛分布的有毒环境污染物。利用质子核磁共振波谱和UPLC-MS，我们获得了暴露于亚致死浓度镉的模式生物秀丽隐杆线虫的代谢谱。无论是存在还是不存在镉，金属硫蛋白状态（单或双mtl敲除）都不会显着调节代谢谱。然而，与菌株无关，镉暴露导致半胱硫氨酸浓度降低，非核糖体合成肽植物螯合蛋白-2和植物螯合蛋白-3增加。这表明，对低水平镉的主要反应是秀丽隐杆线虫反硫途径的差异调节，该途径将甲硫氨酸通过半胱氨酸转运到植物螯合素合成。这些结果得到了植物螯合素合成酶突变体（pcs-1）对镉的敏感性至少比单金属硫蛋白或双金属硫蛋白突变体高一个数量级的发现的支持。然而，在mtl-1中观察到对镉的添加剂敏感性；Mtl-2，- pcs-1三重突变体。
Cadmium is a widely distributed toxic environmental pollutant. Using proton NMR spectroscopy and UPLC-MS, we obtained metabolic profiles from the model organism Caenorhabditis elegans exposed to sublethal concentrations of cadmium. Neither in the presence nor absence of cadmium did the metallothionein status (single or double mtl knockouts) markedly modulate the metabolic profile. However, independent of strain, cadmium exposure resulted in a decrease in cystathionine concentrations and an increase in the nonribosomally synthesized peptides phytochelatin-2 and phytochelatin-3. This suggests that a primary response to low levels of cadmium is the differential regulation of the C. elegans trans-sulfuration pathway, which channels the flux from methionine through cysteine into phytochelatin synthesis. These results were backed up by the finding that phytochelatin synthase mutants (pcs-1) were at least an order of magnitude more sensitive to cadmium than single or double metallothionein mutants. However, an additive sensitivity toward cadmium was observed in the mtl-1; mtl-2,- pcs-1 triple mutant.