title: Silver ion-induced suicidal erythrocyte death.
abstract: Owing to its antibiotic activity, silver is used for water purification, wound care and a wide variety of implants. Silver metal and silver compounds ionize in solution, and silver ions interfere with the function of a wide variety of proteins. In mammalian cells, silver ions may trigger apoptosis by stimulation of cytochrome c release from mitochondria. The present study explored the effect of AgNO3 on eryptosis, the suicidal death of erythrocytes, cells devoid of mitochondria. Similar to apoptosis of nucleated cells, eryptosis is characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine exposure at the cell surface. Eryptosis is triggered by energy depletion, cellular depletion of nitric oxide (NO) and activation of protein kinase C (PKC). Phosphatidylserine exposure was determined by annexin V-binding, cell volume by forward scatter, cellular ATP by a luciferin-luciferase assay kit, and hemolysis by photometry. A 48 h exposure to AgNO3 (> or =100 nm) but not to NaNO3 significantly enhanced the percentage of annexin V-binding cells, slightly but significantly decreased forward scatter and significantly decreased cytosolic ATP. Furthermore, inhibition of PKC by staurosporine and donation of NO by sodium nitroprusside significantly blunted silver-induced eryptosis. In conclusion, AgNO3 triggers cell membrane scrambling, an effect attributed to ATP depletion, PKC activation and decrease of cellular NO.
authors.affiliation: Department of Physiology, University of Tübingen, Gmelinstr. 5, D-72076 Tübingen, Germany.
authors.forename: Mentor
authors.initials: M
authors.lastname: Sopjani
authors.forename: Michael
authors.initials: M
authors.lastname: Föller
authors.forename: Judith
authors.initials: J
authors.lastname: Haendeler
authors.forename: Friedrich
authors.initials: F
authors.lastname: Götz
authors.forename: Florian
authors.initials: F
authors.lastname: Lang
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D017302:Annexins / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D048429:Cell Size / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004910:Erythrocyte Membrane / Q000187:drug effects* / Q000378:metabolism; D004912:Erythrocytes / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007477:Ions / Q000494:pharmacology*; D010718:Phosphatidylserines / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D018030:Silver Compounds / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D017302:Annexins; D007477:Ions; D010718:Phosphatidylserines; D018030:Silver Compounds; D000255:Adenosine Triphosphate; D002118:Calcium