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Stimulation of erythrocyte phosphatidylserine exposure by mercury ions

2005; Elsevier BV; Volume: 210; Issue: 1-2 Linguagem: Inglês

10.1016/j.taap.2005.07.022

1096-0333

Kerstin Eisele, Philipp A. Lang, Daniela S. Kempe, Barbara A. Klarl, Olivier M Niemöller, Thomas Wieder, Stephan M. Huber, Christophe Duranton, Florian Läng,

Phagocytosis and Immune Regulation

The sequelae of mercury intoxication include induction of apoptosis. In nucleated cells, Hg2+-induced apoptosis involves mitochondrial damage. The present study has been performed to elucidate effects of Hg2+ in erythrocytes which lack mitochondria but are able to undergo apoptosis-like alterations of the cell membrane. Previous studies have documented that activation of a Ca2+-sensitive erythrocyte scramblase leads to exposure of phosphatidylserine at the erythrocyte surface, a typical feature of apoptotic cells. The erythrocyte scramblase is activated by osmotic shock, oxidative stress and/or energy depletion which increase cytosolic Ca2+ activity and/or activate a sphingomyelinase leading to formation of ceramide. Ceramide sensitizes the scramblase to Ca2+. The present experiments explored the effect of Hg2+ ions on erythrocytes. Phosphatidylserine exposure after mercury treatment was estimated from annexin binding as determined in FACS analysis. Exposure to Hg2+ (1 μM) indeed significantly increased annexin binding from 2.3 ± 0.5% (control condition) to 23 ± 6% (n = 6). This effect was paralleled by activation of a clotrimazole-sensitive K+-selective conductance as measured by patch-clamp recordings and by transient cell shrinkage. Further experiments revealed also an increase of ceramide formation by ∼66% (n = 7) after challenge with mercury (1 μM). In conclusion, mercury ions activate a clotrimazole-sensitive K+-selective conductance leading to transient cell shrinkage. Moreover, Hg2+ increases ceramide formation. The observed mechanisms could similarly participate in the triggering of apoptosis in nucleated cells by Hg2+.