Nerve growth factor-induced neurite formation in PC12 cells is independent of endogenous cellular gangliosides |
| |
Authors: | Li R; Kong Y; Ladisch S |
| |
Institution: | Glycobiology Program, Center for Cancer and Transplantation Biology, Children's Research Institute, The George Washington University School of Medicine, Washington, DC 20010, USA. |
| |
Abstract: | The PC12 rat pheochromocytoma cell line is an established model for nerve
growth factor (NGF)-induced neurite formation. It has been shown that when
gangliosides are added to the culture medium of PC12 cells, NGF-induced
neurite formation of PC12 cells is enhanced. To determine the role of
endogenous cellular gangliosides themselves in NGF-elicited neurite
formation, we depleted cellular gangliosides using the new specific
glucosylceramide synthase inhibitor, d, l-threo-1-phenyl-2-
hexadecanoylamino-3-pyrrolidino-1-propanol.HCl (PPPP). 0.5-2 microM PPPP
rapidly inhibited ganglioside synthesis and depletedcellular gangliosides.
Nonetheless, over a concentration range of 5-100 ng/ml NGF, in both low
serum and serum-free medium, neurite formation was normal. Even
pretreatment of PC12 cells for up to 6 days with 1 microM PPPP followed by
cotreatment with PPPP and NGF for 10 days, still did not inhibit neurite
formation. The conclusion that ganglioside depletion did not block neurite
formation stimulated by NGF was supported by the lack of effect of PPPP,
under these same conditions, on cellular acetylcholine esterase activity, a
neuronal differentiation marker (73.8 +/- 12.1 versus 67.2 +/- 4.6
nmol/min/mg protein at 50 ng/ml NGF; control versus 1 microM PPPP). These
findings, together with previous studies showing enhancement of NGF-induced
neurite formation by exogenous gangliosides, underscore the vastly
different effects that exogenous gangliosides and endogenous gangliosides
may have upon cellular functions.
|
| |
Keywords: | |
本文献已被 Oxford 等数据库收录! |
|