Monitoring and Modulating Intracellular Cholesterol Trafficking Using ALOD4, a Cholesterol-Binding Protein.
Monitoring and Modulating Intracellular Cholesterol Trafficking Using ALOD4, a Cholesterol-Binding Protein. Methods Mol Biol. 2019;1949:153-163 Authors: Endapally S, Infante RE, Radhakrishnan A Abstract Mammalian cells carefully control their cholesterol levels by employing multiple feedback mechanisms to regulate synthesis of cholesterol and uptake of cholesterol from circulating lipoproteins. Most of a cell's cholesterol (~80% of total) is in the plasma membrane (PM), but the protein machinery that regulates cellular cholesterol resides in the endoplasmic reticulum (ER) membrane, which contains a very small fraction (~1% of total) of a cell's cholesterol. How does the ER communicate with PM to monitor cholesterol levels in that membrane? Here, we describe a tool, ALOD4, that helps us answer this question. ALOD4 traps cholesterol at the PM, leading to depletion of ER cholesterol without altering total cell cholesterol. The effects of ALOD4 are reversible. This tool has been used to show that the ER is able to continuously sample cholesterol from PM, providing ER with information about levels of PM cholesterol. PMID: 30790255 [PubMed - indexed for MEDLINE]
Publication date: Available online 24 September 2020Source: Saudi Journal of Biological SciencesAuthor(s): Nora A. AlFaris, Ghedeir M. Alshammari, Jozaa Z. AlTamimi, Lujain A. AlMousa, Nora M. AlKehayez, Dalal H. Aljabryn, Reham I. Alagal, Mohammed A. Yahya
CONCLUSION: In a country with no national FH screening program, our pilot project demonstrated that implementing a simple phenotypical FH cascade screening strategy using the collaboration of motivated specialists and two nurses, allowed to diagnose FH in 127 index patients and an additional 105 of their relatives over the two-year period. Newly developed MEDPED FH cut-offs, easily applicable by a nurse with a single blood sample, might further improve the sensitivity of detecting FH within families. PMID: 32964780 [PubMed - as supplied by publisher]
Oxidized high-density lipoprotein (oxHDL), unlike native HDL, is characterized by reduced cholesterol efflux capability and anti-inflammatory properties. The ratio of oxHDL to apolipoprotein A-I (oxHDL/apoAI) is a possible marker of dysfunctional HDL. The aim of this study was to evaluate the association between oxHDL/apoAI and coronary plaque characteristics that increase the likelihood of cardiovascular events as determined by coronary computed tomography (CT) angiography.
Abstract A gallbladder (GB) polyp is an elevation of the GB mucosa that protrudes into the GB lumen. GB polyps have an estimated prevalence of 0.3-9.5% and can be divided into neoplastic (true) polyps and nonneoplastic polyps (pseudopolyps). Pseudopolyps are most commonly cholesterol polyps but also include focal adenomyomatosis and inflammatory polyps with no malignant potential. Neoplastic polyps, however, can be benign or malignant. Benign polyps are most commonly adenomas, while malignant polyps are usually adenocarcinoma. Transabdominal ultrasonography is the main radiological modality used for diagnosing and...
Hepatic abundance of the low-density lipoprotein receptor (LDLR) is a critical determinant of circulating plasma LDL cholesterol levels and hence development of coronary artery disease. The sterol-responsive E3 ubiquitin ligase inducible degrader of the LDLR (IDOL) specifically promotes ubiquitination and subsequent lysosomal degradation of the LDLR and thus controls cellular LDL uptake. IDOL contains an extended N-terminal FERM (4.1 protein, ezrin, radixin, and moesin) domain, responsible for substrate recognition and plasma membrane association, and a second C-terminal RING domain, responsible for the E3 ligase activity ...
Strong evidence suggests that dysregulated lipid metabolism involving dysfunction of the retinal pigmented epithelium (RPE) underlies the pathogenesis of age-related macular degeneration (AMD), the leading cause of irreversible blindness in the elderly. A hallmark of AMD is the overproduction of lipid- and protein-rich extracellular deposits that accumulate in the extracellular matrix (Bruch's membrane (BrM)) adjacent to the RPE. We analyzed apolipoprotein A-1 (ApoA-1)-containing lipoproteins isolated from BrM of elderly human donor eyes and found a unique proteome, distinct from high-density lipoprotein (HDL) isolated fro...
the ORION 10-11 trials have reported the efficacy of Inclisiran on low-density lipoprotein cholesterol (LDLc) reduction, and also suggested prevention of major cardiovascular events (MACE) incidence.
The accumulation of low-density lipoproteins (LDL) in the arterial wall plays a pivotal role in the initiation and pathogenesis of atherosclerosis. Conversely, the removal of cholesterol from the intima by cholesterol efflux to high density lipoproteins (HDL) and subsequent reverse cholesterol transport shall confer protection against atherosclerosis. To reach the subendothelial space, both LDL and HDL must cross the intact endothelium. Traditionally, this transit is explained by passive filtration.
HIGH cholesterol doesn't usually produce any symptoms but it does pave the way for heart disease. Simple dietary tweaks can lower your cholesterol, including eating daily servings of a particular snack.