Gangliosides prevent the inhibition by K-252a of NGF responses in PC12 cells.
K-252a, a general kinase inhibitor, selectively blocks the actions of nerve growth factor (NGF) in PC12 cells. Since gangliosides have been reported to modulate neuronal cell responsiveness to NGF and to regulate several protein kinases, the ability of these compounds to reverse the inhibition by K-252a was tested. Parameters at both short- and long-term times following treatment of PC12 cells with NGF were analyzed which are known to be either transcription-dependent or -independent events. Gangliosides were found to completely prevent the inhibition by K-252a of NGF-induced neurite regeneration and c-fos induction, and partially also that of protein kinase N activation. The ganglioside protective effects were concentration-dependent and required the intact molecule. These findings raise the possibility that gangliosides might affect a specific pathway of NGF responses sensitive to inhibition by K-252a.
Ferrari
G
G
Fidia Research Laboratories, Abano Terme, Italy.
Fabris
M
M
Fiori
M G
MG
Gabellini
N
N
Volontè
C
C
D000818:Animals; D002227:Carbazoles / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D005732:Gangliosides / Q000494:pharmacology*; D026121:Indole Alkaloids; D009414:Nerve Growth Factors / Q000037:antagonists & inhibitors*; D009416:Nerve Regeneration / Q000187:drug effects; D016501:Neurites / Q000187:drug effects; D016716:PC12 Cells / Q000187:drug effects / Q000378:metabolism*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D011494:Protein Kinases / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism
D002227:Carbazoles; D005732:Gangliosides; D026121:Indole Alkaloids; D009414:Nerve Growth Factors; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; C049985:staurosporine aglycone; D011494:Protein Kinases; C061570:protein kinase N; D011493:Protein Kinase C