| Ganglioside GM3, a simple ganglioside containing single sialic acid, plays important roles in many cellular behaviors. In the last decade, accumulating data indicate that the concentration of serum GM3in the bloods of cancer or type2diabetes patients or in the plaques of atherosclerotic patients increases dramatically. However, it remains unclear what effects the high GM3concentration will exert on the structure/functions of vascular endothelial cells or on the initiation/progression of atherosclerosis.The integrity and permeability of the endothelium (vascular endothelial cell monolayer) play an important role in atherosclerosis. Cell death, adhesion, spreading, and migration of vascular endothelial cells play important roles in maintaining the integrity and permeability of the endothelium. Firstly, we investigated the effects of exogenous GM3on cell behaviors (cell death, spreading, and migration) of normal endothelial cells. Next, the effects of exogenous GM3on the Ox-LDL-treated endothelial cells, which simulates the situation of atherosclerosis, were studied. Then, mβCD, a cholesterol-depleting reagent, was used to disrupt lipid rafts in the plasma membrane of cells to detect the potential mechanism of the GM3effects.Our data show that exogenous GM3significantly killed cells, inhibited cell spreading, and promoted cell migration, indicating that exogenous GM3is potentially able to destroy the integrity of endothelium. In agreement with previous studies, Ox-LDL treatment could also cause the damage of the integrity of endothelium. We found that exogenous GM3could enhance this Ox-LDL-induced damage, implying that exogenous GM3is potentially able to promote the initiation/progression of atherosclerosis. The mβCD experiments show that the disruption of lipid rafts in cellular plasma membrane reversed the GM3effects on both normal and Ox-LDL-treated endothelial cells, implying that the mechanism of the GM3effects potentially correlates with lipid rafts. |
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