Abstract:
:The NGF secretion from cultured mouse astrocytes was enhanced by sublethal concentrations of phosphatidic acid (PA), ceramide, or sphingosine (Sph), and concentration dependently by lysophosphatidic acid (LPA), sphingosylphosphorylcholine (SPC), or sphingosine-1-phosphate (S1P), but was unaffected by any concentrations of phosphatidylcholine (PC), phosphatidylethanolamine (PE) or sphingomyelin (SM). The enhancement of NGF synthesis by Sph was completely inhibited by the addition of ceramide synthase inhibitor, fumonisin B1. LPA and S1P showed similar hyperbolic curves with maximum NGF secretion at concentrations of more than 50 microM, but they showed no proliferative effect on quiescent astrocytes. The mechanisms underlying the stimulation of NGF synthesis by 50 microM LPA and 50 microM S1P were further investigated by using various inhibitors. One of the protein kinase C (PKC) inhibitors, Gö6976, suppressed the LPA- and S1P-stimulated NGF synthesis by 70 and 80%, respectively. LPA and S1P were found to activate common multiple signaling pathways for NGF production, involving the activation of the protein kinase C (PKC), mitogen-activated protein (MAP) kinase, and phosphatidylinositol 3-kinase (PI-3K) pathways.
journal_name
Mol Cell Biochemjournal_title
Molecular and cellular biochemistryauthors
Furukawa A,Kita K,Toyomoto M,Fujii S,Inoue S,Hayashi K,Ikeda Kdoi
10.1007/s11010-007-9524-4subject
Has Abstractpub_date
2007-11-01 00:00:00pages
27-34issue
1-2eissn
0300-8177issn
1573-4919journal_volume
305pub_type
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