We used electrophoretic mobility shift assays to investigate the effects of cobalamin (Cbl) deficiency on the levels of activated nuclear factor-kappa B (NF-kappaB) 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-kappaB 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-kappaB 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)-alpha and nerve growth factor (NGF) levels in the SC (each of which is a known NF-kappaB activator), we redetermined NF-kappaB levels in the SCs and livers of TGX rats treated with anti-TNF-alpha or anti-NGF antibodies and found that NF-kappaB levels normalized in both tissues after either treatment. These results demonstrate that: (1) Cbl physiologically and indirectly down-regulates NF-kappaB levels in rat SC and liver, and (2) NF-kappaB is an important signaling molecule after Cbl deficiency injury.
Indirect down-regulation of nuclear NF-kB levels by cobalamin in the spinal cord and liver of the rat / D. Veber, E. Mutti, L. Tacchini, E. Gammella, G. Tredici, G. Scalabrino. - In: JOURNAL OF NEUROSCIENCE RESEARCH. - ISSN 0360-4012. - 86:6(2008 May 01), pp. 1380-1387.
|Titolo:||Indirect down-regulation of nuclear NF-kB levels by cobalamin in the spinal cord and liver of the rat|
VEBER, DANIELA (Primo)
MUTTI, ELENA (Secondo)
SCALABRINO, GIUSEPPE (Ultimo)
|Settore Scientifico Disciplinare:||Settore MED/04 - Patologia Generale|
|Data di pubblicazione:||1-mag-2008|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1002/jnr.21599|
|Appare nelle tipologie:||01 - Articolo su periodico|