Details

Autor(en) / Beteiligte

• Lang, Karl
• Roll, Benjamin
• Myssina, Svetlana
• Schittenhelm, Markus
• Scheel-Walter, Hans-Gerhard
• Kanz, Lothar
• Fritz, Jasmin
• Lang, Florian
• Huber, Stephan
• Wieder, Thomas

Titel

Enhanced Erythrocyte Apoptosis in Sickle Cell Anemia, Thalassemia and Glucose-6-Phosphate Dehydrogenase Deficiency

Ist Teil von

• Cellular physiology and biochemistry, 2002-01, Vol.12 (5-6), p.365-372

Ort / Verlag

Basel, Switzerland

Erscheinungsjahr

2002

Quelle

MEDLINE

Beschreibungen/Notizen

• Erythrocyte diseases such as sickle cell anemia, thalassemia and glucose-6-phosphate dehydrogenase deficiency decrease the erythrocyte life span, an effect contributing to anemia. Most recently, erythro-cytes have been shown to undergo apoptosis upon increase of cytosolic Ca 2+ activity. The present study has been performed to explore whether sickle cell anemia, thalassemia and glucose-6-phosphate dehydrogenase deficiency enhance the sensitivity of erythrocytes to osmotic shock, oxidative stress or energy depletion, all maneuvers known to increase cytosolic Ca 2+ activity. To this end, annexin binding as an indicator of apoptosis has been determined by FACS analysis. Erythrocytes from healthy individuals, from patients with sickle cell anemia, thalassemia or glucose-6-phosphate dehydrogenase deficiency all responded to osmotic shock (up to 950 mOsm by addition of sucrose for 24 hours), to oxidative stress (up to 1.0 mM tetra-butyl-hydroxyperoxide tBOOH) and to energy depletion (up to 48 hours glucose deprivation) with enhanced annexin binding. However, the sensitivity of sickle cells and of glucose-6-phosphate dehydrogenase deficient cells to osmotic shock and of sickle cells, thalassemic cells and glucose-6-phosphate dehydrogenase deficient cells to oxidative stress and to glucose depletion was significantly higher than that of control cells. Annexin binding was further stimulated by Ca 2+ ionophore ionomycin with significantly higher sensitivity of sickle cells and glucose-6-phosphate dehydrogenase deficient cells as compared to intact cells. In conclusion, sickle cells, thalassemic cells and glucose-6-phosphate dehydrogenase deficient erythrocytes are more sensitive to osmotic shock, oxidative stress and/or energy depletion, thus leading to enhanced apoptosis of those cells. The accelerated apoptosis then contributes to the shortened life span of the defective erythrocytes.