Abstract
Plasmalopsychosine, a characteristic fatty aldehyde conjugate of beta-galactosylsphingosine (psychosine) found in brain white matter, enhances p140trk (Trk A) phosphorylation and mitogen-activated protein kinase (MAPK) activity and as a consequence induces neurite outgrowth in PC12 cells. The effect of plasmalopsychosine on neurite outgrowth and its prolonged activation of MAPK was similar to that of nerve growth factor (NGF), and the effect was specific to neuronal cells. Plasmalopsychosine was not capable of competing with cold chase-stable, high affinity binding of NGF to Trk A, indicating that plasmalopsychosine and NGF differ in terms of Trk A-activating mechanism. Tyrosine kinase inhibitors K-252a and staurosporine, known to inhibit the neurotrophic effect of NGF, also inhibited these effects of plasmalopsychosine, suggesting that plasmalopsychosine and NGF share a common signaling cascade. Plasmalopsychosine prevents apoptosis of PC12 cells caused by serum deprivation, indicating that it has "neurotrophic factor-like" activity. Taken together, these findings indicate that plasmalopsychosine may play an important role in development and maintenance of the vertebrate nervous system.
Highlights
Plasmalopsychosine, a characteristic fatty aldehyde conjugate of -galactosylsphingosine found in brain white matter, enhances p140trk (Trk A) phosphorylation and mitogen-activated protein kinase (MAPK) activity and as a consequence induces neurite outgrowth in PC12 cells
nerve growth factor (NGF) induces signal transduction through activation of tyrosine kinase associated with its receptor p140trk (Trk A) [5, 6] and causes a phenotypic change of PC12 cells involving neurite outgrowth, which has been regarded as a criterion of neuronal cell differentiation [7, 8]
Neuritogenesis was not observed after treatment with EGF, psychosine (Fig. 2, B and C), GM1 ganglioside, lysophosphatidic acid, and galactocerebroside
Summary
(Received for publication, June 27, 1995, and in revised form, November 6, 1995). Chouhei Sakakura‡, Yasuyuki Igarashi, Jasbir K. Plasmalopsychosine prevents apoptosis of PC12 cells caused by serum deprivation, indicating that it has “neurotrophic factor-like” activity. NGF induces signal transduction through activation of tyrosine kinase associated with its receptor p140trk (Trk A) [5, 6] and causes a phenotypic change of PC12 cells involving neurite outgrowth, which has been regarded as a criterion of neuronal cell differentiation [7, 8]. Psychosine is known to inhibit kinase C [1, 14] and mitochondrial cytochrome c oxidase [19] Based on this background, we studied the effect of PLPS on neuronal differentiation and associated transmembrane signal changes in PC12 cells
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