title: Indirect down-regulation of nuclear NF-kappaB levels by cobalamin in the spinal cord and liver of the rat.
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-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.
authors.affiliation: Institute of General Pathology, University of Milan, Milan, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Veber
authors.forename: Elena
authors.initials: E
authors.lastname: Mutti
authors.forename: Lorenza
authors.initials: L
authors.lastname: Tacchini
authors.forename: Elena
authors.initials: E
authors.lastname: Gammella
authors.forename: Giovanni
authors.initials: G
authors.lastname: Tredici
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Scalabrino
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002467:Cell Nucleus / Q000378:metabolism; D015536:Down-Regulation; D024202:Electrophoretic Mobility Shift Assay; D005743:Gastrectomy; D008099:Liver / Q000378:metabolism*; D008297:Male; D016328:NF-kappa B / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000378:metabolism*; D050863:Synaptotagmin I / Q000378:metabolism; D014805:Vitamin B 12 / Q000378:metabolism*; D014806:Vitamin B 12 Deficiency / Q000503:physiopathology*
chemical_list: D016328:NF-kappa B; D050863:Synaptotagmin I; D014805:Vitamin B 12