Diminished iron concentrations increase adenosine A2A receptor levels in mouse striatum and cultured human neuroblastoma cells
Diminished iron concentrations increase adenosine A2A receptor levels in mouse striatum and cultured human neuroblastoma cells
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DOI：
10.1016/j.expneurol.2008.10.007
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发表时间：
2009-02-01
影响因子：
5.3
通讯作者：
Mattson, Mark R.
中科院分区：
文献类型：
--
作者：
Gulyani, Seema;Earley, Christopher J.;Mattson, Mark R.
脑铁不足与几种神经系统疾病有关。在啮齿类动物模型的铁缺乏研究中，多巴胺系统一直在改变。纹状体多巴胺D-2受体的变化与铁缺乏的程度成正比。鉴于铁缺乏-多巴胺连接的未知机制，以及纹状体中腺苷能和多巴胺能系统之间已知的相互作用，我们研究了铁缺乏对腺苷系统的影响。我们首先试图评估是否有腺苷受体水平的功能变化，以响应这种低铁。与正常饮食的小鼠相比，通过饮食使铁缺乏的小鼠纹状体腺苷A（2A）（A（2A）R）的密度增加，但不是A1受体（A（1）R）。在正常饮食条件下，两个近交系小鼠纹状体铁浓度相差2倍，纹状体铁含量较低的品系具有最高的纹状体A（2A）R密度。用铁螯合剂处理SH-SY 5 Y（人神经母细胞瘤）细胞导致A（2A）R密度增加。在这些细胞中，A（2A）R激动剂诱导的环AMP产生响应于铁螯合而增强，也证明AMR的功能性上调。细胞铁状态的主要标志物转铁蛋白受体（TfR）和A（2A）R蛋白密度之间存在显著相关性（r（2）=0.79）。总之，在不同的缺铁条件下，A（2A）R会增加。A（2A）R与细胞铁状态的关系可能是腺苷改变多巴胺能系统功能的重要途径。(c)2008年爱思唯尔公司All rights reserved.
Brain iron insufficiency has been implicated in several neurological disorders. The dopamine system is consistently altered ill Studies of iron deficiency in rodent models. Changes in striatal dopamine D-2 receptors are directly proportional to the degree of iron deficiency. In light of the unknown mechanism for the iron deficiency-dopamine connection and because of the known interplay between adenosinergic and dopaminergic systems in the striatum we examined the effects of iron deficiency on the adenosine system. We first attempted to assess whether there is a functional change in the levels of adenosine receptors in response to this low iron. Mice made iron-deficient by diet had an increase in the density of striatal adenosine A(2A) (A(2A)R) but not A, receptor (A(1)R) compared to mice on a normal diet. Between two inbred murine Strains, which had 2-fold differences in their striatal iron concentrations under normal dietary conditions, the strain with the lower striatal iron had the highest striatal A(2A)R density. Treatment of SH-SY5Y (human neuroblastoma) cells with an iron chelator resulted in increased density of A(2A)R. In these cells, A(2A)R agonist-induced cyclic AMP production was enhanced in response to iron chelation, also demonstrating a functional upregulation of AMR. A significant correlation (r(2)=0.79) was found between a primary marker of cellular iron status (transferrin receptor (TfR)) and A(2A)R protein density. In conclusion, the A(2A)R is increased across different iron-insufficient conditions. The relation between A(2A)R and cellular iron status may be an important pathway by which adenosine may alter the function of the dopaminergic system. (c) 2008 Elsevier Inc. All rights reserved.