The 17-kDa endogenous brain protein glia maturation factor (GMF) was transfected into C6 @entity35 @entity11 cells using a replication-defective @entity1 adenovirus vector. The cells overexpressed GMF but did not secrete the protein into the medium. Transfection with GMF led to the activation of the transcription factor nuclear factor-kappaB (NF-kappaB), as evidenced by electrophoretic mobility shift assay of the nuclear extract, using a double-stranded oligonucleotide probe containing the consensus binding sequence for NF-kappaB. The specificity of binding was demonstrated by competition with unlabeled probe and by the nonbinding of the mutant probe. Binding was detectable as early as 3 h after transfection, peaked at 6 and 12 h, and gradually declined thereafter. The observed NF-kappaB activation was reduced by cotransfection with catalase and by the presence of high concentrations of @entity2388 in the medium, suggesting the involvement of @entity274 . The @entity12220 mitogen-activated protein kinase inhibitor @entity1441 also suppressed the GMF-activated NF-kappaB, suggesting the involvement of the @entity12220 signal transduction cascade. On the other hand, the @entity10757 ester @entity1359 activated NF-kappaB whether or not GMF was overexpressed. Along with NF-kappaB activation was an enhanced expression of @entity224 dismutase (SOD), which was suppressed if NF-kappaB nuclear translocation was blocked by its specific decoy DNA, implicating NF-kappaB as an upstream mediator of this antioxidant enzyme. The @entity12220 inhibitor @entity1441 also blocked the GMF-activated SOD. As NF-kappaB and SOD are both pro-survival signals, the results suggest a cytoprotective role for endogenous GMF in glial cells.

Activation of nuclear factor-kappaB in C6 @entity35 XXXX cells after transfection with glia maturation factor.

@entity1 :: ('9606', 'Species') :: ['human'] @entity274 :: ('CHEBI:16240', 'Chemical') :: ['H2O2'] @entity10757 :: ('MESH:C033085', 'Chemical') :: ['phorbol'] @entity1441 :: ('MESH:C093642', 'Chemical') :: ['SB-203580'] @entity1359 :: ('CHEBI:37537', 'Chemical') :: ['phorbol 12-myristate 13-acetate'] @entity11 :: ('MESH:D005910', 'Disease') :: ['glioma'] @entity224 :: ('MESH:D013481', 'Chemical') :: ['superoxide'] @entity35 :: ('10116', 'Species') :: ['rat'] @entity12220 :: ('81649(Tax:10116)', 'Gene') :: ['p38'] @entity2388 :: ('MESH:D019289', 'Chemical') :: ['pyruvate']
@entity11 :: (MESH:D005910,Disease) :: ['glioma']
