title: Stimulation of suicidal erythrocyte death by methylglyoxal.
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 Ca(2+)-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 microM) encountered in diabetic patients. Surprisingly, methylglyoxal did not significantly increase cytosolic Ca(2+) concentration, and at concentrations up to 3 microM, 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.
authors.affiliation: Department of Physiology, University of Tübingen, Tübingen, Germany.
authors.forename: Jan P
authors.initials: JP
authors.lastname: Nicolay
authors.forename: Juliane
authors.initials: J
authors.lastname: Schneider
authors.forename: Olivier M
authors.initials: OM
authors.lastname: Niemoeller
authors.forename: Ferruh
authors.initials: F
authors.lastname: Artunc
authors.forename: Manuel
authors.initials: M
authors.lastname: Portero-Otin
authors.forename: George
authors.initials: G
authors.lastname: Haik
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Thornalley
authors.forename: Erwin
authors.initials: E
authors.lastname: Schleicher
authors.forename: Thomas
authors.initials: T
authors.lastname: Wieder
authors.forename: Florian
authors.initials: F
authors.lastname: Lang
mesh_terms: D017304:Annexin A5 / Q000378:metabolism; D001786:Blood Glucose / Q000378:metabolism; D016923:Cell Death; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000150:complications; D004912:Erythrocytes / Q000187:drug effects*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D008875:Middle Aged; D010718:Phosphatidylserines / Q000378:metabolism*; D011765:Pyruvaldehyde / Q000097:blood / Q000633:toxicity*
chemical_list: D017304:Annexin A5; D001786:Blood Glucose; D010718:Phosphatidylserines; D011765:Pyruvaldehyde