Effects of exogenous gangliosides on intracellular Ca2+ mobilization and functional responses in human platelets.
Gangliosides, highly expressed in the outer leaflet of plasma membranes, mediate a variety of biological processes, including cell-cell and cell-matrix interactions. We examined the effects of exogenous gangliosides on intracellular Ca2+ mobilization and functional responses in human platelets. Gangliosides (GM3 and GM1) induced rapid and reversible elevation of intracellular Ca2+ in fura2-loaded platelets in a concentration-dependent manner. The Ca(2+)-mobilizing effect of gangliosides was not mimicked by deN-acetyl-GM3, lactosylceramide, or free sialic acid, suggesting that structural integrity as ganglioside is essential for this effect. GM3 and GM1 also induced platelet shape change by themselves and elicited aggregation in combination with epinephrine. Our observations suggest the involvement of ganglioside-activated platelets in atherosclerosis, in view of the high observed ganglioside levels in atherosclerotic lesions of human aorta.
Yatomi
Y
Y
Biomembrane Institute, Seattle, WA 98119, USA.
Igarashi
Y
Y
Hakomori
S
S
D000818:Animals; D001161:Arteriosclerosis / Q000209:etiology; D001792:Blood Platelets / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D002118:Calcium / Q000097:blood*; D048429:Cell Size / Q000187:drug effects; D004285:Dogs; D004837:Epinephrine / Q000494:pharmacology; D005677:G(M1) Ganglioside / Q000494:pharmacology; D005679:G(M3) Ganglioside / Q000494:pharmacology; D005732:Gangliosides / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007424:Intracellular Fluid / Q000378:metabolism; D017136:Ion Transport / Q000187:drug effects; D015539:Platelet Activation / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects; D015398:Signal Transduction
D005679:G(M3) Ganglioside; D005732:Gangliosides; D005677:G(M1) Ganglioside; D002118:Calcium; D004837:Epinephrine