NPC1 and NPC2 Regulate Cellular Cholesterol Homeostasis through Generation of Low Density Lipoprotein Cholesterol-derived Oxysterols

NPC1 and NPC2 regulate cellular cholesterol homeostasis through generation of low density lipoprotein cholesterol-derived oxysterols.

Mutations in the Niemann-Pick disease genes cause lysosomal cholesterol accumulation and impaired low density lipoprotein (LDL) cholesterol esterification. These findings have been attributed to a block in cholesterol movement from lysosomes to the site of the sterol regulatory machinery. In this study we show that Niemann-Pick type C1 (NPC1) and Niemann-Pick type C2 (NPC2) mutants have increas...

cholesterol/high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, non–high-density lipoprotein cholesterol, or low-density lipoprotein particle concentration and guideline categories of low-density lipoprotein cholesterol or non–high-density lipoprotein cholesterol

International clinical practice guidelines on dyslipidemia emphasize the importance of matching the use and intensity of statin therapy with the absolute risk of atherosclerotic cardiovascular disease (CVD). Indeed, independent of the baseline level of dyslipidemia, patients who have entered the intervention arms of randomized clinical trials of statin therapy with similar absolute risks of CVD...

Do oxysterols control cholesterol homeostasis?

Low-Density Lipoprotein Receptor (LDLR) Family Orchestrates Cholesterol Homeostasis

The LDLR family of proteins is involved in lipoproteins trafficking. While the role of LDLR in cardiovascular disease has been widely studied, only recently the role of other members of the LDLR proteins in lipoprotein homeostasis and atherosclerosis has emerged. LDLR, VLDLR, and LRPs bind and internalize apoE- and apoB-containing lipoprotein, including LDL and VLDL, and regulate their cellular...

Niemann-pick type C1 (NPC1) overexpression alters cellular cholesterol homeostasis.

The Niemann-Pick type C1 (NPC1) protein is a key participant in intracellular trafficking of low density lipoprotein cholesterol, but its role in regulation of sterol homeostasis is not well understood. To characterize further the function of NPC1, we generated stable Chinese hamster ovary (CHO) cell lines overexpressing the human NPC1 protein (CHO/NPC1). NPC1 overexpression increases the rate ...