g(m1)-ganglioside and Arteriosclerosis

Sialidase activity has been determined in homogenates of human aortic intima by measuring the amount of GM1 formed during the incubation of ganglioside GD1a with the tissue homogenates. Areas with atherosclerotic lesions as well as adjacent areas without histological evidence of atherosclerosis were taken for comparison. The rate of GM1 formation from GD1a in the presence of homogenates of the atherosclerotic intima was 20 pmol/h per mg protein. Homogenates of the unaffected intima did not desialylate GD1a. Sialidase activity of the atherosclerotic intima was linear for 1.5 h at GD1a content up to 1.5 nmol and at homogenate protein up to 1 micro g. NH4Cl and NeuAc2en, inhibitors of lysosomal function and plasma membrane-bound sialidase, respectively, reduced sialidase activity of homogenates of the atherosclerotic intima by 94%. The results indicate that atherosclerotic lesions and unaffected intima differ in their activity and specificity of sialidases that cleave gangliosides.

Topics: Adult; Aged; Ammonium Chloride; Aorta; Arteriosclerosis; Azides; Cell Membrane; Enzyme-Linked Immunosorbent Assay; Female; G(M1) Ganglioside; Gangliosides; Humans; Male; Middle Aged; Neuraminidase; Sialic Acids; Tunica Intima

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.

Topics: Animals; Arteriosclerosis; Blood Platelets; Calcium; Cell Size; Dogs; Epinephrine; G(M1) Ganglioside; G(M3) Ganglioside; Gangliosides; Humans; In Vitro Techniques; Intracellular Fluid; Ion Transport; Platelet Activation; Platelet Aggregation; Signal Transduction