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 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.
Sakakura
C
C
Biomembrane Institute, Seattle, Washington 98119-4237, USA.
Igarashi
Y
Y
Anand
J K
JK
Sadozai
K K
KK
Hakomori
S
S
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001923:Brain Chemistry; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D006801:Humans; D009414:Nerve Growth Factors / Q000378:metabolism* / Q000494:pharmacology; D016501:Neurites / Q000187:drug effects; D016716:PC12 Cells; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011609:Psychosine / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism*; D015398:Signal Transduction
D009414:Nerve Growth Factors; D017475:Receptors, Nerve Growth Factor; D011609:Psychosine; D011505:Protein-Tyrosine Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases