Plasmalopsychosine of human brain mimics the effect of nerve growth factor by activating its receptor kinase and mitogen-activated protein kinase in PC12 cells. Induction of neurite outgrowth and prevention of apoptosis

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...

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Bibliographic Details
Published in:The Journal of biological chemistry 1996-01, Vol.271 (2), p.946-952
Main Authors: Sakakura, C, Igarashi, Y, Anand, J K, Sadozai, K K, Hakomori, S
Format: Article
Language:English
Subjects:
Animals
Apoptosis - drug effects
Brain Chemistry
Calcium-Calmodulin-Dependent Protein Kinases - metabolism
Humans
Nerve Growth Factors - metabolism
Nerve Growth Factors - pharmacology
Neurites - drug effects
PC12 Cells
Protein-Tyrosine Kinases - metabolism
Psychosine - metabolism
Psychosine - pharmacology
Rats
Receptors, Nerve Growth Factor - metabolism
Signal Transduction
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Summary: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.
ISSN:0021-9258
DOI:10.1074/jbc.271.2.946