Nonenzymatic glycosylation of erythrocyte membrane proteins. Relevance to diabetes
UMass Chan Affiliations
Department of Medicine, Division of RheumatologyDocument Type
Journal ArticlePublication Date
1980-04-01Keywords
Anemia, HemolyticBlood Proteins
Borohydrides
Diabetes Complications
Diabetes Mellitus
Erythrocyte Membrane
Erythrocytes
Glycoproteins
Humans
In Vitro Techniques
Membrane Proteins
nonenzymatic glycosylation
proteins
diabetes
Amino Acids, Peptides, and Proteins
Biochemistry
Cellular and Molecular Physiology
Endocrinology
Endocrinology, Diabetes, and Metabolism
Hemic and Lymphatic Diseases
Nutritional and Metabolic Diseases
Metadata
Show full item recordAbstract
Nonenzymatic glycosylation of proteins of the erythrocyte membrane was determined by incubating erythrocyte ghosts with [3H]borohydride. The incorporation of tritium into protein provides a reliable assay of ketoamine linkages. The membrane proteins from 18 patients with diabetes incorporated twice as much radioactivity as membrane proteins from normal erythrocytes. After acid hydrolysis, amino acid analysis showed that the majority of radioactivity was localized to glucosyllysine. Autoradiograms showed that all of the major proteins of the erythrocyte membrane, separated by electrophoresis on sodium dodecyl sulfate gels, contained ketoamine linkages. No protein bands in either normal or diabetic erythrocytes showed significant preferential labeling. Erythrocyte membranes from three patients with hemolytic anemia showed reduced incorporation of tritium from [3H]-borohydride, indicating decreased nonenzymatic glycosylation. Two patients with diabetes and hemolytic anemia had incorporation of radioactivity similar to that of normal individuals. In these groups of patients the incorporation of tritium into erythrocyte membrane proteins correlated with levels of hemoglobin AIc. Thus the modification of membrane proteins like that of hemoglobin depends on blood glucose levels as well as erythrocyte age. These studies show that the enhanced nonenzymatic glycosylation of proteins in diabetics extends beyond hemoglobin to the proteins of the erythrocyte membrane and probably affects other proteins that have slow turnover and are exposed to high concentrations of glucose.Source
J Clin Invest. 1980 Apr;65(4):896-901. Link to article on publisher's siteDOI
10.1172/JCI109743Permanent Link to this Item
http://hdl.handle.net/20.500.14038/48754PubMed ID
7358849Notes
At the time of publication, Ellen Gravallese was not yet affiliated with the University of Massachusetts Medical School.
Related Resources
Link to Article in PubMedRights
Publisher PDF posted as allowed by the publisher's author rights policy at http://static.the-jci.org/content_assets/admin/forms/jcicopyright.pdf.
ae974a485f413a2113503eed53cd6c53
10.1172/JCI109743
Scopus Count
Collections
Related items
Showing items related by title, author, creator and subject.
-
Uniporters and anion antiportersHebert, Daniel N; Carruthers, Anthony (1991-08-01)The past year has seen a flurry of activity in the area of protein-mediated hexose uniport. Topics of interest covered here include: structure-function studies; the interaction of glucose carriers with glycolytic enzymes; regulation of cell surface glucose-carrier concentrations by insulin and the signalling mechanisms involved; and the role of the glucose-carrier isoform, GLUT2, in pancreatic beta-cell glucose-dependent insulin secretion. Nucleoside uniport and Glu-Asp antiport are also discussed briefly.
-
Endoplasmic reticulum stress in beta-cells and development of diabetesFonseca, Sonya G.; Burcin, Mark; Gromada, Jesper; Urano, Fumihiko (2009-08-12)The endoplasmic reticulum (ER) is a cellular compartment responsible for multiple important cellular functions including the biosynthesis and folding of newly synthesized proteins destined for secretion, such as insulin. A myriad of pathological and physiological factors perturb ER function and cause dysregulation of ER homeostasis, leading to ER stress. ER stress elicits a signaling cascade to mitigate stress, the unfolded protein response (UPR). As long as the UPR can relieve stress, cells can produce the proper amount of proteins and maintain ER homeostasis. If the UPR, however, fails to maintain ER homeostasis, cells will undergo apoptosis. Activation of the UPR is critical to the survival of insulin-producing pancreatic beta-cells with high secretory protein production. Any disruption of ER homeostasis in beta-cells can lead to cell death and contribute to the pathogenesis of diabetes. There are several models of ER-stress-mediated diabetes. In this review, we outline the underlying molecular mechanisms of ER-stress-mediated beta-cell dysfunction and death during the progression of diabetes.
-
Transient high glucose causes persistent epigenetic changes and altered gene expression during subsequent normoglycemiaEl-Osta, Assam; Brasacchio, Daniella; Yao, Dachun; Pocai, Alessandro; Jones, Peter L.; Roeder, Robert G.; Cooper, Mark E.; Brownlee, Michael (2008-09-29)The current goal of diabetes therapy is to reduce time-averaged mean levels of glycemia, measured as HbA1c, to prevent diabetic complications. However, HbA1c only explains <25% of the variation in risk of developing complications. Because HbA1c does not correlate with glycemic variability when adjusted for mean blood glucose, we hypothesized that transient spikes of hyperglycemia may be an HbA1c-independent risk factor for diabetic complications. We show that transient hyperglycemia induces long-lasting activating epigenetic changes in the promoter of the nuclear factor kappaB (NF-kappaB) subunit p65 in aortic endothelial cells both in vitro and in nondiabetic mice, which cause increased p65 gene expression. Both the epigenetic changes and the gene expression changes persist for at least 6 d of subsequent normal glycemia, as do NF-kappaB-induced increases in monocyte chemoattractant protein 1 and vascular cell adhesion molecule 1 expression. Hyperglycemia-induced epigenetic changes and increased p65 expression are prevented by reducing mitochondrial superoxide production or superoxide-induced alpha-oxoaldehydes. These results highlight the dramatic and long-lasting effects that short-term hyperglycemic spikes can have on vascular cells and suggest that transient spikes of hyperglycemia may be an HbA1c-independent risk factor for diabetic complications.