Dehydration-induced proteome changes in the rat hypothalamo-neurohypophyseal system
Dehydration-induced proteome changes in the rat hypothalamo-neurohypophyseal system
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DOI：
10.1210/en.2007-0181
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发表时间：
2007-07-01
期刊：
影响因子：
4.8
通讯作者：
Murphy, D.
中科院分区：
文献类型：
--
作者：
Gouraud, S. S.;Heesom, K.;Murphy, D.
下丘脑-神经垂体系统（HNS）通过抗利尿激素血管加压素（VP）的作用介导神经内分泌对脱水的反应。VP作为前原肽的一部分在下丘脑视上核和室旁核的大细胞神经元中合成。该前体在运输至垂体后叶中的轴突末端期间被加工，其中生物活性VP被储存，直到被渗透性线索诱发的电活动动员用于分泌。在释放过程中，VP通过血流到达位于肾脏中的特定受体靶点，在该靶点中，VP增加集合管对水的渗透性，减少肾脏的水排泄，从而促进水的保护。HNS在脱水过程中经历了戏剧性的功能相关的可塑性。我们推测稳态蛋白水平的改变可能是这种重塑的部分原因。我们研究了脱水引起的SON和垂体神经中间叶（NIL）蛋白质组的变化，使用二维荧光差异凝胶电泳。70种蛋白质被脱水改变，包括NIL中的45种和SON中的25种。使用基质辅助激光解吸/电离质谱法，我们确定了6个蛋白质在NIL（四个下降，两个上升）和9个蛋白质在SON（四个上升，五个下降）的调节作为慢性脱水的结果。其中五种蛋白质的结果，即Hsp 1 α（热休克蛋白1 α），NAP 22（神经元轴突膜蛋白22），GRP 58（58 kDa葡萄糖调节蛋白）、钙视网膜蛋白和ProSAAS（前蛋白转化酶枯草杆菌蛋白酶/kexin 1型抑制剂），已经使用独立的方法如半定量Western印迹，二维Western印迹，酶联免疫测定，和免疫组织这些蛋白可能在调节和影响HNS重塑中起作用。
The hypothalamo-neurohypophyseal system (HNS) mediates neuroendocrine responses to dehydration through the action of the antidiuretic hormone vasopressin (VP). VP is synthesized as part of a prepropeptide in magnocellular neurons of the hypothalamic supraoptic nucleus (SON) and paraventricular nucleus. This precursor is processed during transport to axon terminals in the posterior pituitary gland, in which biologically active VP is stored until mobilized for secretion by electrical activity evoked by osmotic cues. During release, VP travels through the blood stream to specific receptor targets located in the kidney in which it increases the permeability of the collecting ducts to water, reducing the renal excretion of water, thus promoting water conservation. The HNS undergoes a dramatic function-related plasticity during dehydration. We hypothesize that alterations in steady-state protein levels might be partially responsible for this remodeling. We investigated dehydration-induced changes in the SON and pituitary neurointermediate lobe (NIL) proteomes using two-dimensional fluorescence difference gel electrophoresis. Seventy proteins were altered by dehydration, including 45 in the NIL and 25 in the SON. Using matrix-assisted laser desorption/ionization mass spectrometry, we identified six proteins in the NIL (four down, two up) and nine proteins in the SON (four up, five down) that are regulated as a consequence of chronic dehydration. Results for five of these proteins, namely Hsp1 alpha (heat shock protein 1 alpha), NAP22 (neuronal axonal membrane protein 22), GRP58 (58 kDa glucose regulated protein), calretinin, and ProSAAS (proprotein convertase subtilisin/kexin type 1 inhibitor), have been confirmed using independent methods such as semiquantitative Western blotting, two-dimensional Western blotting, enzyme-linked immunoassay, and immunohistochemistry. These proteins may have roles in regulating and effecting HNS remodeling.