Lipoproteins and Cellular Cholesterol Homeostasis

Acute Tubular Injury Causes Dysregulation of Cellular Cholesterol Transport Proteins

“…In contrast to ABCA-1 and SR-B1, the LDL receptor (LDL-R) facilitates cellular cholesterol uptake. 17 Given these considerations, it would be predicted that a normal compensatory response to increased renal tubular cell cholesterol synthesis would be increased ABCA-1, increased SR-B1, and decreased LDL-R expression.…”

Amphotericin B Inhibits the Generation of the Scrapie Isoform of the Prion Protein in Infected Cultures

“…A more complete analysis of PrP trafficking upon AmB treatment (endocytosis, recycling, and cleavage) is needed to identify the exact site of action of the drug. Finally, the fact that a cholesterol gradient appears to exist from the internal organelles to the cell membrane (2,25) could explain why the generation of PrP Sc is affected only partially and temporarily by AmB. In fact, at the concentration used in this work, the external membranes would have been the principal target of the drug (53) and any alternate intracellular conversion pathway of PrP C , as has been suggested previously to occur (48), would have gone unaffected.…”

Changes in Free and Esterified Cholesterol

“…These include extracellular cholesterol uptake via the LDL receptor pathway, de novo cholesterol synthesis, intracellular cholesterol trafficking (among organellar, cytosolic, and plasma membrane pools), cellular efflux, and cholesterol esterification/deacylation reactions. 18,32,33 Under normal circumstances, these pathways are exquisitively balanced, resulting in tight regulation of both total cell cholesterol content and stable free versus esterified cholesterol pools. As examples, if cholesterol uptake is increased (eg, via increased LDL cholesterol presentation to the plasma membrane LDL receptor), a reciprocal decrease in cholesterol synthesis occurs (regulated by decreased HMG-CoA reductase activity).…”

“…(Of note in this regard is that our previous cholesterol assessments 2 were performed using a commercially available enzymatic assay which measures only total cholesterol content, ie, the sum of FC ϩ EC.) Fourth, given that tissue cholesterol increments can arise from increased uptake, ie, via low density lipoprotein, (LDL) receptors, decreased efflux, or de novo synthesis, 18 it remains to be seen which mechanism(s) are responsible for cholesterol accumulation in the cytoresistant state. The following studies were performed to provide insights into each of these four issues.…”