Indirect down-regulation of nuclear NF-κB levels by cobalamin in the spinal cord and liver of the rat

✍ Scribed by Daniela Veber; Elena Mutti; Lorenza Tacchini; Elena Gammella; Giovanni Tredici; Giuseppe Scalabrino

• Publisher: John Wiley and Sons
• Year: 2008
• Tongue: English
• Weight: 497 KB
• Volume: 86
• Category: Article
• ISSN: 0360-4012
• DOI: 10.1002/jnr.21599

✦ Synopsis

Abstract

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.