earticle

영어

Glucosylceramide synthase (GCS) catalyzes glycosylation of ceramide and produces glucosylceramide. Ceramide accumulation in cells induces apoptosis, and its glycosylation make it possible to escape from ceramide-induced apoptosis. In some cases, it was reported GCS can lead to multidrug resistance of cancer cells and its depletion cause neuronal defect in brains. Previous report indicates Glycolipids, especially glucosylceramide (GluCer), Lactosylceramide (LacCer) and GM3 ganglioside was accumulated in atherosclerotic lesion. In the atherosclerosis, TNF-α was a prominent inducer of proliferation and migration of vascular smooth muscle cells (VSMC). Reasonably TNF-α does not stimulate apoptotic signals in VSMCs. In our results, we found TNF-α induced the expression of GCS and stimulated ganglioside production in HASMCs. GCS expression was inhibited by a MAPKinase inhibitor, U0126. In addition, PDMP, a GCS inhibitor, suppressed the TNF-α induced proliferation of HASMCs. Taken together, it is supposed GCS is a gatekeeper of TNF-α induced cell proliferation and ganglioside production in atherosclerotic lesion.