The existence of glucosylated cholesterol (GlcChol) in tissue has recently been recognized. GlcChol is generated from glucosylceramide (GlcCer) and cholesterol through transglucosylation by two retaining β-glucosidases, GBA and GBA2. Given the abundance of GBA, GlcCer and cholesterol in the skin's stratum corneum (SC), we studied the occurrence of GlcChol. A significant amount of GlcChol was detected in SC (6 pmol/mg weight). The ratio GlcChol/GlcCer is higher in SC than epidermis, 0.083 and 0.011, respectively. Examination of GlcChol in patients with Netherton syndrome revealed comparable levels (11 pmol/mg). Concluding, GlcChol was identified as a novel component in SC and is likely locally metabolized by GBA. The physiological function of GlcChol in the SC warrants future investigation.
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http://dx.doi.org/10.1016/j.cca.2020.09.017 | DOI Listing |
Biomacromolecules
January 2025
Institute of Macromolecular Chemistry, CAS, Heyrovského nám. 2, Praha 6 162 06, Czech Republic.
Multifunctional polymers are interesting substances for the formulation of drug molecules that cannot be administered in their pure form due to their pharmacokinetic profiles or side effects. Polymer-drug formulations can enhance pharmacological properties or create tissue specificity by encapsulating the drug into nanocontainers, or stabilizing nanoparticles for drug transport. We present the synthesis of multifunctional poly(2-ethyl-2-oxazoline--2-glyco-2-oxazoline)s containing two reactive end groups, and an additional hydrophobic anchor at one end of the molecule.
View Article and Find Full Text PDFiScience
October 2024
Department of Pharmacological and Biomolecular Sciences "Rodolfo Paoletti", Università degli Studi di Milano, via Balzaretti, 9, Milan, Italy.
The present study describes and compares the impact of PCSK9 and LDLR, two pivotal players in cholesterol metabolism, on the whole lipidome of plasma, liver and aorta in different dietary conditions. This issue is relevant, since several lipid species, circulating at very low concentrations, have the ability to impair lipid metabolism and promote atherosclerosis development. To this aim, wild-type, hypercholesterolemic Ldlr-KO, and hypocholesterolemic Pcsk9-KO mice were fed a standard chow or a Western-type diet up to 30 and 16 weeks of age, respectively.
View Article and Find Full Text PDFNaunyn Schmiedebergs Arch Pharmacol
December 2024
Institute of Experimental and Clinical Pharmacology, Toxicology and Pharmacology of Natural Products, Ulm University Medical Center, Albert-Einstein-Allee 11, 89081, Ulm, Germany.
The dreaded nosocomial pathogen Clostridioides difficile causes diarrhea and severe inflammation of the colon, especially after the use of certain antibiotics. The bacterium releases two deleterious toxins, TcdA and TcdB, into the gut, which are mainly responsible for the symptoms of C. difficile-associated diseases (CDADs).
View Article and Find Full Text PDFGut Microbes
December 2023
Institute of Experimental and Clinical Pharmacology, Toxicology and Pharmacology of Natural Products, Ulm University Medical Center, Ulm, Germany.
The intestinal pathogen is the leading cause of antibiotic-associated diarrhea and pseudomembranous colitis in humans. The symptoms of -associated diseases (CDADs) are directly associated with the pathogen's toxins TcdA and TcdB, which enter host cells and inactivate Rho and/or Ras GTPases by glucosylation. Membrane cholesterol is crucial during the intoxication process of TcdA and TcdB, and likely involved during pore formation of both toxins in endosomal membranes, a key step after cellular uptake for the translocation of the glucosyltransferase domain of both toxins from endosomes into the host cell cytosol.
View Article and Find Full Text PDFBiochem Biophys Rep
July 2023
Escuela de Nutrición y Dietética, Universidad de Antioquia, Apartado, 1226, Medellín, Colombia.
Plant bioactive compounds such as flavonoids and triterpenes can affect lipid metabolism. Here, we report the cytotoxic and lipid-lowering activities of the ethanolic extract of leaves on human colon adenocarcinoma SW480 cells, also the molecular interactions of bioactive compounds present in extract on ACC and HMGCR enzymes. The extract reduced cell viability and decreased intracellular triglyceride content by up to 35% and 28% at 24 and 48 h, respectively; whereas the effect was evident on cholesterol only at 24 h.
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