Effect of short-term hyperglycemia on protein kinase C alpha activation in human erythrocytes

Rev Diabet Stud. 2012 Summer-Fall;9(2-3):94-103. doi: 10.1900/RDS.2012.9.94. Epub 2012 Nov 15.

Abstract

Background: Diabetes mellitus, characterized by chronic hyperglycemia, is known to have a deleterious effect on erythrocyte structure and hemodynamic characteristics, which eventually contribute to diabetes-associated vascular complications. Protein kinase C alpha (PKCα) is a major regulator of many metabolic processes and structural changes in erythrocytes, and may play a significant role in the development of hyperglycemia-mediated cellular abnormalities.

Aim: We hypothesized that acute hyperglycemic stress may affect erythrocyte structure and metabolic properties through its effect on PKCα membrane content and activity.

Results: Erythrocytes, from healthy individuals acutely exposed to a glucose enriched media, showed a significant decrease in the membranous fraction of PKCα and its phosphorylation (p = 0.005 and p = 0.0004, respectively). These alterations correlated with decreased affinity of PKCα to its membrane substrates (4.1R and GLUT1) and reduced RBC deformability (p = 0.017). Pre-activation of erythrocytes with PKC activator, PMA, minimized the effect of glucose on the membrane PKCα fraction and RBC deformability (p > 0.05).

Conclusions: Acute glycemia-induced inhibition of PKCα membranous translocation and activation is associated with reduced erythrocyte membrane deformability.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Enzyme Activation
  • Erythrocyte Membrane / enzymology*
  • Erythrocyte Membrane / ultrastructure
  • Female
  • Humans
  • Hyperglycemia / blood*
  • Hyperglycemia / enzymology*
  • Immunoblotting
  • Male
  • Middle Aged
  • Protein Kinase C-alpha / metabolism*
  • Tetradecanoylphorbol Acetate / pharmacology

Substances

  • Protein Kinase C-alpha
  • Tetradecanoylphorbol Acetate