Effect of Short-Term Hyperglycemia on Protein Kinase C Alpha Activation in Human Erythrocytes

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Abstract
The Review of Diabetic Studies,2012,9,2-3,94-103.
Published:November 2012
Type:Original Article
Authors:
Author(s) affiliations:

Leonid Livshits1, Ariel Srulevich1, Itamar Raz1, Avivit Cahn2, Gregory Barshtein3, Shaul Yedgar3 and Roy Eldor1

1The Diabetes Research Center, Hadassah Hebrew University Medical Center, Jerusalem, Israel.

2Endocrinology and Metabolism Service, Hadassah Hebrew University Medical Center, Jerusalem, Israel.

3Department of Biochemistry, Hadassah Hebrew University Medical Center, Jerusalem, Israel.

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