Tag Archives: ER-associated protein degradation
Serum glycomarkers of endoplasmic reticulum and lysosomal-endosomal system stress in human healthy aging and diseases
I. U. Pismenetskaya1, T. D. Butters2
1SI Dnepropetrovsk Medical Academy, Ukraine;
2CarboNet Consulting Ltd., Oxford, UK
e-mail: ip01589@gmail.com
To verify the idea that extracellular free oligosaccharides might be able to reflect the functional status of the endoplasmic reticulum (ER) and lysosomal-endosomal system, HPLC-profiles of serum-derived free oligosaccharides (FOS) in human healthy aging, acute myeloproliferative neoplasms, and cardiovascular pathologies were compared with intracellular glycans. After plasma deproteinization and FOS purification the oligosaccharides were labelled with anthranilic acid, separated into the neutral and charged with QAE Sephadex (Q25-120) chromatography and analysed using high-performance liquid chromatography (HPLC). The charged FOS were digested with a sialidase and compared with free oligosaccharides from transferrin for structural decoding. HPLC-profiles of serum-derived FOS revealed mild delay of the dolichol phosphate cycle in ER, moderate intensification of ER-associated degradation (ERAD) and degradation in endosomal-lysosomal system with aging; an inhibition of the dolichol phosphate cycle, intensification of ERAD and increasing of lysosomal exocytosis in acute myeloproliferative neoplasms; intensification of ERAD and glycocojugate degradation with endosomal-lysosomal system in cardiovascular diseases. As serum free oligosaccharides are able to reflect specifically perturbations in ER and endosomal-lysosomal system under wide range of stressors they can serve as extracellular markers of functionality of these organelles.
“Three sources and three component parts” of free oligosaccharides
I. U. Pismenetskaya1, T. D. Butters2
1SI Dnepropetrovsk Medical Academy, Ukraine;
2Oxford Glycobiology Institute, University of Oxford, UK;
e-mail: pismenetskaya@yahoo.com
Metabolism of glycoproteins and glycolipids is accompanied by the appearance of unbound structural analogues of the carbohydrate portion of glycoconjugates or so called free oligosaccharides. There are their several sources inside the cell: 1) multistep pathways of N-glycosylation, 2) the cell quality control and ER-associated degradation of misglycosylated and /or misfolded glycoproteins, 3) lysosomal degradation of mature glycoconjugates. In this review the information about the ways of free oligosaccharides appearance in different cell compartments and details of their structures depending on the source is summarized. In addition, extracellular free oligosaccharides, their structures and changes under normal and pathological conditions are discussed.