title: Static magnetic field exposure reproduces cellular effects of the Parkinson's disease drug candidate ZM241385.
abstract: BACKGROUND
  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).
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Biomedical Engineering, The Johns Hopkins University, Baltimore, Maryland, United States of America.
authors.forename: Zhiyun
authors.initials: Z
authors.lastname: Wang
authors.forename: Pao-Lin
authors.initials: PL
authors.lastname: Che
authors.forename: Jian
authors.initials: J
authors.lastname: Du
authors.forename: Barbara
authors.initials: B
authors.lastname: Ha
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Yarema
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D058908:Adenosine A2 Receptor Agonists / Q000494:pharmacology; D058917:Adenosine A2 Receptor Antagonists / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D000242:Cyclic AMP / Q000378:metabolism; D007501:Iron / Q000378:metabolism; D055909:Magnetic Field Therapy / Q000379:methods; D008280:Magnetics; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D016501:Neurites / Q000187:drug effects / Q000378:metabolism; D016716:PC12 Cells; D010300:Parkinson Disease / Q000378:metabolism / Q000628:therapy; D010627:Phenethylamines / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D043705:Receptor, Adenosine A2A / Q000378:metabolism*; D014227:Triazines / Q000494:pharmacology*; D014230:Triazoles / Q000494:pharmacology*
chemical_list: D058908:Adenosine A2 Receptor Agonists; D058917:Adenosine A2 Receptor Antagonists; D010627:Phenethylamines; D043705:Receptor, Adenosine A2A; D014227:Triazines; D014230:Triazoles; C097270:ZM 241385; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; D000255:Adenosine Triphosphate; D000242:Cyclic AMP; D007501:Iron; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D000241:Adenosine; D002118:Calcium