Dioxin alters the human low-density and very low-density lipoprotein structure with evidence for specific quenching of Trp-48 in apolipoprotein C-II

Biochemistry
Eric ArehartHoward Patterson

Abstract

The intercellular transport of cholesterol and triglycerides via lipoproteins interacting with their receptors is a critical component in human lipid metabolism. The delivery of cholesterol to cells is accomplished primarily through low-density lipoproteins (LDLs), while the transport of fatty acids to adipose and muscle tissue is accomplished primarily through the actions of very low-density lipoproteins (VLDLs). Disruption of lipoprotein structure leading to impaired binding between these lipoproteins and their obligate receptors is a known risk factor for cardiovascular disease. Because of recent investigations linking 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure in humans with coronary artery disease, investigations have been carried out by fluorescence and circular dichroism to evaluate conformational changes in LDL and VLDL structure upon binding of TCDD. These studies demonstrate that, at a molar ratio of three TCDD molecules to one lipoprotein molecule, TCDD binds and disrupts the secondary and tertiary lipoprotein structure. Circular dichroism studies show that residues within the inner core of apoC-II, which compose a four-alpha-helix bundle when this apolipoprotein is associated with VLDL, are directly affecte...Continue Reading

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Citations

Mar 29, 2011·Arteriosclerosis, Thrombosis, and Vascular Biology·Dalei WuChristoph Franz Adam Vogel
Feb 8, 2011·Journal of Biomaterials Science. Polymer Edition·Xiaofei LiuBo Wu
Jun 15, 2012·Toxicological Sciences : an Official Journal of the Society of Toxicology·Rachel TanosGary H Perdew
Feb 20, 2007·Nutrition, Metabolism, and Cardiovascular Diseases : NMCD·Bernhard HennigMichal Toborek
Sep 3, 2008·Environmental Research·Philip Sebastian HjelmborgEva Cecilie Bonefeld-Jørgensen

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