In:
Journal of Neurochemistry, Wiley, Vol. 71, No. 2 ( 1998-08), p. 498-505
Abstract:
Abstract: The signal mechanism underlying tumor necrosis factor α (TNFα) up‐regulation of nerve growth factor (NGF) production was studied in primary rat astrocyte cultures. Because ceramide is also able to induce NGF secretion and because TNFα is a known agonist of the sphingomyelin (SPM)‐ceramide pathway, we investigated whether the TNFα‐induced NGF secretion by primary astrocytes is mediated by ceramide. TNFα stimulation of NGF secretion was shown to be independent of protein kinase C, abrogated by the tyrosine phosphoprotein phosphatase inhibitor phenylarsine oxide (PAO), and independent of the activation of the mitogen‐activated protein kinase (MAPK) cascade. In marked contrast, inhibition of MAPK counteracted the NGF secretion induced by ceramide. TNFα stimulation of the nuclear transcription factor NF‐κB was prevented by cell pretreatment with PAO, whereas ceramide and sphingomyelinase had a marginal effect on NF‐κB activation. Moreover, TNFα failed to activate the SPM pathway, as indicated by the lack of SPM degradation and the absence of ceramide generation. To clarify further the role of NF‐κB in NGF synthesis, electrophoretic mobility shift assays were performed with an NF‐κB site from the NGF promoter. The absence of significant binding of NF‐κB to the NGF gene promoter indicates the existence of an indirect role of NF‐κB in the regulation of NGF synthesis. Altogether, our data strongly suggest that TNFα‐mediated up‐regulation of NGF occurs independently of ceramide generation.
Type of Medium:
Online Resource
ISSN:
0022-3042
,
1471-4159
DOI:
10.1046/j.1471-4159.1998.71020498.x
Language:
English
Publisher:
Wiley
Publication Date:
1998
detail.hit.zdb_id:
80158-6
detail.hit.zdb_id:
2020528-4
SSG:
12
