Zn homeostasis in genetic models of Parkinson's disease in Caenorhabditis elegans
Zn homeostasis in genetic models of Parkinson's disease in Caenorhabditis elegans
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DOI：
10.1016/j.jtemb.2019.05.005
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发表时间：
2019-09-01
影响因子：
3.5
通讯作者：
Bornhorst, Julia
中科院分区：
文献类型：
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作者：
Baesler, Jessica;Kopp, Johannes F.;Bornhorst, Julia
虽然帕金森病（PD）的潜在机制仍然没有得到充分的研究，但强调了遗传和环境因素之间的复杂相互作用。然而，必需微量元素锌（Zn）在这方面的作用仍然存在争议。在这项研究中，我们改变了多功能模式生物秀丽隐杆线虫（C。elegans），以检查与PD相关的选定基因中的遗传倾向是否影响Zn稳态。蛋白质结合的和不稳定的锌物种在各个领域发挥作用，如酶催化，蛋白质稳定途径和细胞信号传导。因此，总锌和不稳定锌定量测定活线虫作为锌的吸收和生物利用度的个人生物标志物与电感耦合等离子体串联质谱（ICP-MS/MS）或多孔法使用荧光探针ZinPyr-1。年轻和中年缺失突变体catp-6和pdr-1，这是哺乳动物ATP 13 A2（PARK 9）和parkin（PARK 2）的直系同源物，锌暴露后锌稳态改变相比，野生型蠕虫。此外，在野生型蠕虫中观察到锌吸收的年龄特异性差异，以及不稳定的锌物种。这些数据强调了锌物种之间的区分作为锌吸收有意义的生物标志物的重要性，以及需要进一步研究锌稳态失调在PD病因中的作用。
While the underlying mechanisms of Parkinson's disease (PD) are still insufficiently studied, a complex interaction between genetic and environmental factors is emphasized. Nevertheless, the role of the essential trace element zinc (Zn) in this regard remains controversial. In this study we altered Zn balance within PD models of the versatile model organism Caenorhabditis elegans (C. elegans) in order to examine whether a genetic predisposition in selected genes with relevance for PD affects Zn homeostasis. Protein-bound and labile Zn species act in various areas, such as enzymatic catalysis, protein stabilization pathways and cell signaling. Therefore, total Zn and labile Zn were quantitatively determined in living nematodes as individual biomarkers of Zn uptake and bioavailability with inductively coupled plasma tandem mass spectrometry (ICP-MS/MS) or a multi-well method using the fluorescent probe ZinPyr-1. Young and middle-aged deletion mutants of catp-6 and pdr-1, which are orthologues of mammalian ATP13A2 (PARK9) and parkin (PARK2), showed altered Zn homeostasis following Zn exposure compared to wildtype worms. Furthermore, age-specific differences in Zn uptake were observed in wildtype worms for total as well as labile Zn species. These data emphasize the importance of differentiation between Zn species as meaningful biomarkers of Zn uptake as well as the need for further studies investigating the role of dysregulated Zn homeostasis in the etiology of PD.