Original Paper

Stimulation of Suicidal Erythrocyte Death by Methylglyoxal
Jan Nicolay¹, Juliane Schneider¹, Olivier Niemoeller¹, Ferruh Artunc¹, Manuel Portero-Otin², George Haik Jr.³, Paul Thornalley², Erwin Schleicher⁴, Thomas Wieder¹, Florian Lang<sup>1

1</sup>Department of Physiology, and
⁴Department of Internal Medicine, University of Tübingen,
²Department of Biological Sciences, University of Essex,
³George Haik Eye Clinic, New Orleans, Louisiana

Address of Corresponding Author

Cell Physiol Biochem 2006;18:223-232 (DOI: 10.1159/000097669)

  Abstract

Diabetes increases the percentage of circulating erythrocytes exposing phosphatidylserine (PS) at the cell surface. PS-exposing erythrocytes are recognized, bound, engulfed and degraded by macrophages. Thus, PS exposure, a feature of suicidal erythrocyte death or eryptosis, accelerates clearance of affected erythrocytes from circulating blood. Moreover, PS-exposing erythrocytes bind to the vascular wall thus interfering with microcirculation. The present study explored mechanisms involved in the triggering of PS exposure by methylgloxal, an extra- and intracellular metabolite which is enhanced in diabetes. PS exposure, cell size and cytosolic Ca²⁺-activity after methylglyoxal treatment were measured by FACS analysis of annexin V binding, forward scatter and Fluo-3-fluorescence, respectively, and it was shown that the treatment significantly enhanced the percentage of PS-exposing erythrocytes at concentrations (0.3 µM) encountered in diabetic patients. Surprisingly, methylglyoxal did not significantly increase cytosolic Ca²⁺ concentration, and at concentrations up to 3 µM, did not decrease the forward scatter. Instead, exposure to methylglyoxal inhibited glycolysis thus decreasing ATP and GSH concentrations. In conclusion, methylglyoxal impairs energy production and anti-oxidative defense, effects contributing to the enhanced PS exposure of circulating erythrocytes and eventually resulting in anemia and deranged microcirculation.

Copyright © 2006 S. Karger AG, Basel

  Author Contacts

Prof. Dr. Florian Lang
Physiologisches Institut der Universität Tübingen
Gmelinstr. 5, D-72076 Tübingen (Germany)
Tel. +49 7071 29 72194, Fax: +49 7071 29 5618
E-Mail florian.lang@uni-tuebingen.de

  Article Information

Accepted: July 27, 2006
Number of Print Pages : 10