elevation of ceramide in serum lipoproteins during acute phase response to inflammation is accompanied by activation of serine-palmitoyl transferase in liver
elevation of ceramide in serum lipoproteins during acute phase response to inflammation is accompanied by activation of serine-palmitoyl transferase in liver
in vivo intraperitoneal application to apolipoprotein E knockout mice leads to inhibition of atherosclerosis while feeding a high fat diet to the mice, and is associated with reduced plasma glycosphingolipid concentration and reduction of lesions in aorta regions, overview
the inhibition of SPT in hyperlipidemic apolipoprotein E knockout mice lowers plasma sphingolipids and atherogenic plasma lipids leading to the regression of pre-existing atherosclerotic lesions and to the formation of a stable plaque phenotype
enzyme activity is enhanced under stress and in apoptosis, e.g. in pancreatic cells in a model for diabetes, in case of angiotensin II type receptor occupancy
elevation of ceramide in serum lipoproteins during acute phase response to inflammation is accompanied by activation of serine-palmitoyl transferase in liver
myeloid cell-specific serine palmitoyltransferase subunit 2 haploinsufficiency reduces murine atherosclerosis. SPT subunit 2-haploinsufficient (Sptlc2+/-) macrophages have significantly lower SM levels in plasma membrane and lipid rafts. This reduction not only impairs inflammatory responses triggered by TLR4 and its downstream NF-kappaB and MAPK pathways, but also enhances reverse cholesterol transport mediated by ABC transporters. LDL receptor-deficient (Ldlr-/-) mice transplanted with Sptlc2+/- bone marrow cells exhibit significantly fewer atherosclerotic lesions after high-fat and high-cholesterol diet feeding. Additionally, Ldlr-/- mice with myeloid cell-specific Sptlc2 haploinsufficiency exhibit significantly less atherosclerosis than controls. Sptlc2 haploinsufficiency in macrophages leads to significant reductions of SM, glucosylceramide, and GM3 in macrophage plasma membranes and lipid rafts, resulting in altered raft distribution. Detailed phenotype overview
serine palmitoyltransferase is the first and rate-limiting enzyme of the de novo biosynthetic pathway of sphingomyelin. Both serine palmitoyltransferase and sphingomyelin are implicated in the pathogenesis of atherosclerosis, the development of which is driven by macrophages
results show that the inhibition of atherosclerosis by the serine palmitoyltransferase inhibitor myriocin in apolipoprotein-E gene knockout mice is associated with reduced plasma glycosphingolipid and plasma sphingomyelin concentration
Van Echten-Deckert, G.; Zschoche, A.; Bar, T.; Schmidt, R.R.; Raths, A.; Heinemann, T.; Sandhoff, K.
cis-4-Methylsphingosine decreases sphingolipid biosynthesis by specifically interfering with serine palmitoyltransferase activity in primary cultured neurons