GM3 ganglioside inhibits endothelin-1-mediated signal transduction in C6 glioma cells.
We found that sparse and confluent C6 glioma cells differ both in GM3 content, which increases with cell density, and in endothelin-1 (ET-1)-induced phosphoinositide hydrolysis, which was markedly higher in the sparse cells than in the confluent. Also after manipulation of the cellular GM3 content through treatment with exogenous GM3 or with drugs known to affect GM3 metabolism, the ET-1 effect was inversely related to GM3 cellular levels. Cell treatment with an anti-GM3 mAb resulted in the enhancement of ET-1-induced phospholipase C activation and restored the capacity of GM3-treated cells to respond to ET-1. These findings suggest that the GM3 ganglioside represents a physiological modulator of ET-1 signaling in glial cells.
Bassi
R
R
Department of Medical Chemistry and Biochemistry, Study Center for the Functional Biochemistry of Brain Lipids, University of Milan, via Fratelli Cervi 93, LITA-Segrate, 20090 Segrate, Milan, Italy.
Viani
P
P
Giussani
P
P
Riboni
L
L
Tettamanti
G
G
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D019332:Endothelin-1 / Q000494:pharmacology* / Q000502:physiology; D005679:G(M3) Ganglioside / Q000037:antagonists & inhibitors / Q000494:pharmacology* / Q000502:physiology*; D005910:Glioma / Q000503:physiopathology*; D007700:Kinetics; D009457:Neuroglia / Q000187:drug effects / Q000502:physiology; D043265:Phosphatidylinositol Diacylglycerol-Lyase; D010716:Phosphatidylinositols / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D014407:Tumor Cells, Cultured; D010738:Type C Phospholipases / Q000378:metabolism
D000911:Antibodies, Monoclonal; D019332:Endothelin-1; D005679:G(M3) Ganglioside; D010716:Phosphatidylinositols; D010738:Type C Phospholipases; D043265:Phosphatidylinositol Diacylglycerol-Lyase