Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:3.1.1.53 (
sialidase
)
2,694
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Lipoprotein metabolism is an important contributing factor in the development and progression of atherosclerosis. Plasma lipoproteins and their receptors are heavily glycosylated and sialylated, and levels of sialic acids modulate their biological functions. Sialylation is controlled by the activities of sialyltranferases and sialidases. To address the impact of
sialidase
(neu1) activity on lipoprotein metabolism, we have generated a mouse model with a hypomorphic neu1 allele (B6.SM) that displays reduced
sialidase
expression and
sialidase
activity. The objectives of this study are to determine the impact of
sialidase
on the rate of hepatic lipoprotein secretion and lipoprotein uptake. Our results indicate that hepatic levels of cholesterol and triglycerides are significantly higher in B6.SM mice compared with C57Bl/6 mice; however, VLDL-triglyceride production rate is lower. In addition, B6.SM mice show significantly lower levels of hepatic microsomal triglyceride transfer protein (MTP) and active sterol-regulatory element binding protein (SREBP)-2 but higher levels of
diglyceride acyltransferase
(
DGAT
)2; these are all indicative of increased hepatic lipid storage. Rescue of
sialidase
activity in hypomorphic
sialidase
mice using helper-dependent adenovirus resulted in increased VLDL production and an increase in MTP levels. Furthermore, hypomorphic
sialidase
expression results in stabilization of hepatic LDL receptor (LDLR) protein expression, which enhances LDL uptake. These findings provide novel evidence for a central role of
sialidase
in the cross talk between the uptake and production of lipoproteins.
...
PMID:Hypomorphic sialidase expression decreases serum cholesterol by downregulation of VLDL production in mice. 2298 45
