Background: Azathioprine is widely used as an immunosuppressive drug. The side effects of azathioprine include anemia, which has been attributed to bone marrow suppression. Alternatively, anemia could result from accelerated suicidal erythrocyte death or eryptosis, which is characterized by exposure
Silver ion-induced suicidal erythrocyte death
✍ Scribed by Mentor Sopjani; Michael Föller; Judith Haendeler; Friedrich Götz; Florian Lang
- Publisher
- John Wiley and Sons
- Year
- 2009
- Tongue
- English
- Weight
- 256 KB
- Volume
- 29
- Category
- Article
- ISSN
- 0260-437X
- DOI
- 10.1002/jat.1438
No coin nor oath required. For personal study only.
✦ Synopsis
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 AgNO~3~ 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 AgNO~3~ (≥100 nm) but not to NaNO~3~ 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, AgNO~3~ triggers cell membrane scrambling, an effect attributed to ATP depletion, PKC activation and decrease of cellular NO. Copyright © 2009 John Wiley & Sons, Ltd.
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