The disruption in transportation of oxLDL-derived cholesterol and the subsequent lipid accumulation in macrophages are the hallmark events in atherogenesis. Our recent studies demonstrated that lysosomal Ca(2+) messenger of nicotinic acid adenine dinucleotide phosphate (NAADP), an enzymatic product of CD38 ADP-ribosylcyclase (CD38), promoted lipid endocytic trafficking in human fibroblast cells...

AIM To characterize how insulin-like growth factor 2 (IGF2) mRNA binding protein p62/IMP2-2 promotes steatohepatitis in the absence of dietary cholesterol. METHODS Non-alcoholic steatohepatitis (NASH) was induced in wild-type mice and in mice overexpressing p62 specifically in the liver by feeding the mice a methionine and choline deficient (MCD) diet for either two or four weeks. As a contro...

We report a 37-year-old woman with Niemann-Pick disease type C (NPC) 1. At the age of 8 years, she presented slow running followed by both fingers dystonia at the age of 10 years. At the age of 16 years, she developed declined scholastic achievement. On her first visit at the age of 17 years, she showed dystonia, ataxic gait and vertical supranuclear gaze palsy. We suspected it was NPC. She pre...

Caveolae or noncoated plasmalemmal vesicles found in a variety of cells have been implicated in a number of important cellular functions including endocytosis, transcytosis, and potocytosis. Their function in transport across endothelium has been especially controversial, at least in part because there has not been any way to selectively inhibit this putative pathway. We now show that the abili...

BACKGROUND Niemann-Pick disease type C (NPC) is caused by defects in cholesterol efflux from lysosomes due to mutations of genes coding for NPC1 and NPC2 proteins. As a result, massive accumulation of unesterified cholesterol in late endosomes/lysosomes is observed. At the level of the organism these cholesterol metabolism disorders are manifested by progressive neurodegeneration and hepatosple...

The γ-butyrolactone autoregulator receptor has been shown to control secondary metabolism and/or morphological differentiation across many Streptomyces species. Streptomyces avermitilis produces an important anthelmintic agent (avermectin) and two further polyketide antibiotics, filipin and oligomycin. Genomic analysis of S. avermitilis revealed that this micro-organism has the clustered putati...

The kinetics of the hemolysis induced by filipin is of the damage type, indicating the formation of large nonselective perforations of erythrocyte membranes. The process is relatively independent of the ionic composition of the incubation medium, and the differences between the hemolysis induced by filipin in pig and human erythrocytes are not significant. In a sucrose medium, filipin-induced h...

The distribution of cholesterol in cells of the stria vascularis of guinea pigs and gerbils has been investigated at the ultrastructural level by incubation of tissue in filipin, followed by freeze-fracture. Verification of results has been sought by using tomatin. It is shown that in the cell body region of the marginal cells, the apical and lateral membranes reacted intensely with both agents...

Niemann-Pick disease, type C (NP-C), is caused by NPC1 or NPC2 gene mutations. Progressive neurological, psychiatric, and visceral symptoms are characteristic. Here, we present cases of a brother (Case 1) and sister (Case 2) in their mid-20s with gait disturbance and psychosis. For the Case 1, neurological examination revealed dystonia, ataxia, vertical supranuclear-gaze palsy (VSGP), and globa...

BACKGROUND/AIMS F508delCFTR-, but not wtCFTR-, expressing fibroblasts resemble Niemann Pick type C cells in the massive intracellular accumulation of free cholesterol. The recruitment and activation of F508delCFTR by cholesterol depletion was studied. METHODS Filipin staining, forskolin-stimulated anion efflux and FITC-dextran uptake were studied in control cells and fibroblasts treated with ...