Indirect down‐regulation of nuclear NF‐κB levels by cobalamin in the spinal cord and liver of the rat
Indirect down‐regulation of nuclear NF‐κB levels by cobalamin in the spinal cord and liver of the rat
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DOI：
10.1002/jnr.21599
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发表时间：
2008-05
影响因子：
4.2
通讯作者：
D. Veber;E. Mutti;L. Tacchini;Elena Gammella;G. Tredici;G. Scalabrino
中科院分区：
文献类型：
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作者：
D. Veber;E. Mutti;L. Tacchini;Elena Gammella;G. Tredici;G. Scalabrino
我们使用电泳迁移率变动分析来研究钴胺素（Cbl）缺乏对通过全胃切除术或Cbl‐D饮食使Cbl‐ D缺乏（Cbl‐D）的大鼠脊髓（SC）和肝脏中活化的核因子-κ B（NF-κB）水平的影响。我们选择SC和肝脏，因为它们分别受到Cbl缺乏在组织学损伤方面的严重或几乎不受影响。我们发现两种类型的Cbl‐D大鼠的SC和肝脏中NF-κB水平（特别是p50和p65亚基）永久性增加，Western印迹分析表明p65水平增加。当用Cbl替代治疗全胃切除（TGX）大鼠时，NF-κB和p65蛋白水平正常化。由于我们之前已经证明Cbl缺乏会增加SC中肿瘤坏死因子（TNF）-α和神经生长因子（NGF）的水平（每种都是已知的NF-κB激活剂），我们重新测定了用抗TNF-α或抗NGF抗体处理的TGX大鼠的SC和肝脏中的NF-κB水平，发现两种处理后两种组织中的NF-κB水平均正常化。这些结果表明：（1）Cbl在生理上间接下调大鼠SC和肝脏中的NF-κB水平;（2）NF-κB是Cbl缺乏损伤后的重要信号分子。© 2008 Wiley利斯公司
We used electrophoretic mobility shift assays to investigate the effects of cobalamin (Cbl) deficiency on the levels of activated nuclear factor‐kappa B (NF‐κB) in the spinal cords (SCs) and livers of rats made Cbl‐deficient (Cbl‐D) by total gastrectomy or a Cbl‐D diet. We chose the SC and liver because they are severely or scarcely affected, respectively, by Cbl deficiency in terms of histological damage. We found permanently increased NF‐κB levels (particularly the p50 and p65 subunits) in the SCs and livers of both types of Cbl‐D rats, and Western blot analysis demonstrated increased p65 levels. NF‐κB and p65 protein levels normalized when the totally gastrectomized (TGX) rats were treated with Cbl replacement. As we have previously demonstrated that Cbl deficiency increases tumor necrosis factor (TNF)–α and nerve growth factor (NGF) levels in the SC (each of which is a known NF‐κB activator), we redetermined NF‐κB levels in the SCs and livers of TGX rats treated with anti‐TNF‐α or anti‐NGF antibodies and found that NF‐κB levels normalized in both tissues after either treatment. These results demonstrate that: (1) Cbl physiologically and indirectly down‐regulates NF‐κB levels in rat SC and liver, and (2) NF‐κB is an important signaling molecule after Cbl deficiency injury. © 2008 Wiley‐Liss, Inc.