Mechanism of Action of Niacin

Kamanna, Vaijinath S.; Kashyap, Moti L.

doi:10.1016/j.amjcard.2008.02.029

Cited by 372 publications

(219 citation statements)

References 42 publications

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“…To confirm that lipid interaction is an essential step in the process of hexamer formation and secretion, we made use of chemical inhibitors targeting lipid components of lipid droplets or lipid rafts. Niacin is an inhibitor of diacylglycerol acyltransferase 2, which prevents triglyceride synthesis (36). Methyl-β-cyclodextrin (MβCD) mobilizes cholesterol, and possibly phospholipids, thus modifying the composition of lipids in both raft and non-raft domains (37).…”

Section: Ns1 Protein Is Secreted As a Lipoprotein Particle Rich In Trmentioning

confidence: 99%

Secreted dengue virus nonstructural protein NS1 is an atypical barrel-shaped high-density lipoprotein

Gutsche

Coulibaly

Voss

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

263

294

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Dengue virus (DENV) causes the major arboviral disease of the tropics, characterized in its severe forms by signs of hemorrhage and plasma leakage. DENV encodes a nonstructural glycoprotein, NS1, that associates with intracellular membranes and the cell surface. NS1 is eventually secreted as a soluble hexamer from DENV-infected cells and circulates in the bloodstream of infected patients. Extracellular NS1 has been shown to modulate the complement system and to enhance DENV infection, yet its structure and function remain essentially unknown. By combining cryoelectron microscopy analysis with a characterization of NS1 amphipathic properties, we show that the secreted NS1 hexamer forms a lipoprotein particle with an open-barrel protein shell and a prominent central channel rich in lipids. Biochemical and NMR analyses of the NS1 lipid cargo reveal the presence of triglycerides, bound at an equimolar ratio to the NS1 protomer, as well as cholesteryl esters and phospholipids, a composition evocative of the plasma lipoproteins involved in vascular homeostasis. This study suggests that DENV NS1, by mimicking or hijacking lipid metabolic pathways, contributes to endothelium dysfunction, a key feature of severe dengue disease.arbovirus | dengue hemorrhagic fever | amphiphilic proteins | secretion

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Section: Ns1 Protein Is Secreted As a Lipoprotein Particle Rich In Trmentioning

confidence: 99%

Secreted dengue virus nonstructural protein NS1 is an atypical barrel-shaped high-density lipoprotein

Gutsche

Coulibaly

Voss

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

263

294

View full text Add to dashboard Cite

show abstract

“…In the liver, nicotinic acid inhibits diacylglycerol acyltransferase-2 (DGAT-2), resulting in decreased secretion of VLDL particles from the liver, which is also reflected in reductions of both IDL and LDL particles. 277 Nicotinic acid raises HDL-C and apoA1 primarily by stimulating apoA1 production in the liver. 277 The effects of nicotinic acid on lipolysis and fatty acid mobilization in adipocytes are well established.…”

Section: Adverse Effects and Interactionsmentioning

confidence: 99%

ESC/EAS Guidelines for the management of dyslipidaemias

Catapano¹,

Reiner²,

Backer³

et al. 2011

Atherosclerosis

565

189

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“…Recent studies indicate that niacin increases vascular endothelial cell redox state, resulting in the inhibition of oxidative stress (Kamanna and Kashyap 2008). These effects were investigated by Ganji et al in vitro, who showed that in cultured endothelial cells niacin increases NADPH levels and reduces GSH (Ganji et al 2009).…”

Section: Niacinmentioning

confidence: 99%