Inhibition of erythrocyte cation channels by erythropoietin
| Autor: | Christina Birka, Björn Friedrich, Florian Lang, Teut Risler, Stephan M. Huber, Thomas Wieder, Svetlana Myssina, Karl S. Lang, Philipp A. Lang |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
medicine.medical_specialty
Phospholipid scramblase Erythrocytes Patch-Clamp Techniques Osmotic shock Cell Culture Techniques Biology chemistry.chemical_compound Phospholipid scrambling Annexin Osmotic Pressure Internal medicine medicine Humans Annexin A5 Phospholipid Transfer Proteins Erythropoietin Membrane Proteins Extracellular Fluid General Medicine Phosphatidylserine Enzyme Activation Red blood cell Endocrinology medicine.anatomical_structure chemistry Nephrology Apoptosis Calcium Channels Carrier Proteins medicine.drug Protein Binding |
| Zdroj: | Journal of the American Society of Nephrology : JASN. 14(11) |
| ISSN: | 1046-6673 |
| Popis: | Recombinant human erythropoietin therapy is used to counteract anemia that is the result of renal insufficiency. It stimulates the formation of peripheral blood erythrocytes by inhibiting apoptosis of erythrocyte precursor cells. Mature erythrocytes have similarly been shown to undergo apoptosis. Hyperosmotic shock and Cl(-) removal activate a Ca(2+)-permeable, ethylisopropylamiloride-inhibitable cation channel. The subsequent increase of cytosolic Ca(2+) activates a scramblase that breaks down cell membrane phosphatidylserine asymmetry, leading to annexin binding. Studied was whether channel activity and erythrocyte cell death are regulated by erythropoietin. Scatchard plot analysis disclosed low-abundance, high-affinity binding of (125)I-erythropoietin to erythrocytes. Whole cell patch clamp experiments revealed significant inhibition of the ethylisopropylamiloride-sensitive current by 1 U/ml erythropoietin. Cl(-) removal triggered annexin binding, an effect abrogated by erythropoietin (1 U/ml) but not by GM-CSF (10 ng/ml). Osmotic shock (700 mOsm) stimulated annexin binding within 24 h in the majority of the erythrocytes, an effect blunted by erythropoietin (1 U/ml) but not by GM-CSF (10 ng/ml). In the nominal absence of Ca(2+), the effect of osmotic shock was blunted and the effect of erythropoietin abolished. In hemodialysis patients, intravenous administration of erythropoietin (50 IU/kg) within 4 h decreased the number of annexin binding circulating erythrocytes. Erythropoietin binds to erythrocytes and inhibits volume-sensitive erythrocyte cation channels and thus the breakdown of phosphatidylserine asymmetry after activation of this channel. The effect could prolong the erythrocyte lifespan and may contribute to the enhancement of the erythrocyte number during erythropoietin therapy in dialysis patients. |
| Databáze: | OpenAIRE |
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