Decreased Ca2(+)-ATPase activity after glycosylation of erythrocyte membranes in vivo and in vitro

Diabetes. 1990 Jun;39(6):707-11. doi: 10.2337/diabetes.39.6.707.

Abstract

Erythrocyte membranes drawn from diabetic patients with poor metabolic control have increased protein glycosylation and decreased Ca2(+)-ATPase activity. A significant relationship was found between these two parameters. Similar results were obtained when protein glycosylation and Ca2(+)-ATPase activity were measured in membranes from normal erythrocytes preincubated with glucose. In this condition, both parameters showed a clear time and dose dependence. Incubation of erythrocyte membranes instead of intact erythrocytes with glucose and glucose-6-phosphate strongly suggests that only the glycosylation of the membrane inner-surface proteins can affect Ca2(+)-ATPase activity. The simultaneous presence of 10 mM glucose and 5 mM ATP in the incubation medium did not affect the degree of erythrocyte membrane protein glycosylation but significantly blocked the inhibitory effect of glucose on Ca2(+)-ATPase activity. However, 5 mM ATP only partially blocked the inhibitory effect of 100 mM glucose, suggesting a competitive mechanism of glucose and ATP for the enzyme active site. Our results show that glycosylation of erythrocyte membrane proteins significantly inhibits Ca2(+)-ATPase activity. This effect could contribute to the development of the capillary closure process observed in diabetic patients. Furthermore, it could represent an index of a general impairment of enzyme function arising in cells chronically exposed to high glucose levels.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Blood Proteins / metabolism
  • Calcium-Transporting ATPases / blood*
  • Culture Media
  • Diabetes Mellitus, Type 1 / blood
  • Dose-Response Relationship, Drug
  • Erythrocyte Membrane / metabolism*
  • Female
  • Glucose / pharmacology
  • Glucose-6-Phosphate
  • Glucosephosphates / pharmacology
  • Glycosylation
  • Humans
  • Hydrogen-Ion Concentration
  • Hyperglycemia / blood
  • Male
  • Middle Aged
  • Reference Values

Substances

  • Blood Proteins
  • Culture Media
  • Glucosephosphates
  • Glucose-6-Phosphate
  • Calcium-Transporting ATPases
  • Glucose