Static magnetic field exposure reproduces cellular effects of the Parkinson's disease drug candidate ZM241385.
Static magnetic field exposure reproduces cellular effects of the Parkinson's disease drug candidate ZM241385.
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DOI：
10.1371/journal.pone.0013883
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发表时间：
2010-11-08
期刊：
影响因子：
3.7
通讯作者：
Yarema KJ
中科院分区：
文献类型：
--
作者：
Wang Z;Che PL;Du J;Ha B;Yarema KJ
这项研究的灵感来自于越来越多的证据表明，磁疗可能是某些疾病的可行治疗选择。这一前提是基于中等强度电场（即0.1至1特斯拉）改变脂质双分子层生物物理特性并进而调节细胞信号通路的能力。特别是，我们实验室之前的结果（Wang等人，BMC Genomics, 10,356(2009)）证实，中等强度的静态磁场（SMF）暴露会改变与神经元功能和分化相关的细胞端点。在此背景下，本论文通过关注显示帕金森病（PD）代谢特征的PC12大鼠肾上腺嗜铬细胞瘤细胞系中的腺苷A2A受体（A2AR）来研究SMF。SMF重现了选择性A2AR拮抗剂ZM241385在PC12细胞中引发的几种反应，包括钙通量改变、ATP水平升高、cAMP水平降低、一氧化氮生成减少、p44/42 MAPK磷酸化减少、增殖抑制和铁摄取减少。SMF还以类似于ZM241385的方式抵消了A2AR激动剂CGS21680加剧的几个pd相关终点；这些包括减少A2AR的增加表达，逆转改变的钙外排，抑制增加的腺苷产生，减少增强的增殖和相关的p44/42 MAPK磷酸化，以及抑制神经突生长。当针对多个终点进行测量时，SMF引起的定性反应与PD候选药物ZM241385相似。如果本文提出的体外结果适用于体内，SMF有望成为治疗PD和其他潜在神经系统疾病的一种有趣的非侵入性方法。
This study was inspired by coalescing evidence that magnetic therapy may be a viable treatment option for certain diseases. This premise is based on the ability of moderate strength fields (i.e., 0.1 to 1 Tesla) to alter the biophysical properties of lipid bilayers and in turn modulate cellular signaling pathways. In particular, previous results from our laboratory (Wang et al., BMC Genomics, 10, 356 (2009)) established that moderate strength static magnetic field (SMF) exposure altered cellular endpoints associated with neuronal function and differentiation. Building on this background, the current paper investigated SMF by focusing on the adenosine A2A receptor (A2AR) in the PC12 rat adrenal pheochromocytoma cell line that displays metabolic features of Parkinson's disease (PD). SMF reproduced several responses elicited by ZM241385, a selective A2AR antagonist, in PC12 cells including altered calcium flux, increased ATP levels, reduced cAMP levels, reduced nitric oxide production, reduced p44/42 MAPK phosphorylation, inhibited proliferation, and reduced iron uptake. SMF also counteracted several PD-relevant endpoints exacerbated by A2AR agonist CGS21680 in a manner similar to ZM241385; these include reduction of increased expression of A2AR, reversal of altered calcium efflux, dampening of increased adenosine production, reduction of enhanced proliferation and associated p44/42 MAPK phosphorylation, and inhibition of neurite outgrowth. When measured against multiple endpoints, SMF elicited qualitatively similar responses as ZM241385, a PD drug candidate. Provided that the in vitro results presented in this paper apply in vivo, SMF holds promise as an intriguing non-invasive approach to treat PD and potentially other neurological disorders.
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