Department of Biomedical Engineering, The Johns Hopkins University, Baltimore, Maryland, United States of America.
PLoS One. 2010 Nov 8;5(11):e13883. doi: 10.1371/journal.pone.0013883.
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 A(2A) receptor (A(2A)R) 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 A(2A)R 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 A(2A)R agonist CGS21680 in a manner similar to ZM241385; these include reduction of increased expression of A(2A)R, 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.
本研究的灵感来源于磁疗可能是某些疾病可行的治疗选择的证据融合。这一前提基于中等强度磁场（即 0.1 至 1 特斯拉）改变脂质双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））表明，中等强度静磁场（SMF）暴露改变了与神经元功能和分化相关的细胞终点。在此背景下，本论文通过聚焦于 PC12 大鼠肾上腺嗜铬细胞瘤细胞系中的腺苷 A（2A）受体（A（2A）R）来研究 SMF，该细胞系显示出帕金森病（PD）的代谢特征。
SMF 在 PC12 细胞中重现了 ZM241385 引发的几种反应，ZM241385 是一种选择性 A（2A）R 拮抗剂，包括改变钙通量、增加 ATP 水平、降低 cAMP 水平、减少一氧化氮产生、减少 p44/42 MAPK 磷酸化、抑制增殖和减少铁摄取。SMF 还以类似于 ZM241385 的方式抵消了 A（2A）R 激动剂 CGS21680 加剧的几种与 PD 相关的终点；这些包括减少 A（2A）R 的表达增加、逆转改变的钙外流、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。
当与多个终点进行比较时，SMF 引发的反应与 PD 药物候选物 ZM241385 相似。如果本文提出的体外结果适用于体内，那么 SMF 有望成为一种有前途的非侵入性方法来治疗 PD 以及可能的其他神经疾病。
