Journal
BASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY
Volume 111, Issue 5, Pages 348-355Publisher
WILEY
DOI: 10.1111/j.1742-7843.2012.00915.x
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Funding
- Deutsche Forschungsgemeinschaft [La 315/4-3, La 315/6-1]
- Bundesministerium fur Bildung, Wissenschaft, Forschung und Technologie (Center for Interdisciplinary Clinical Research)
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Carbon monoxide (CO) intoxication severely interferes with the oxygen-transporting function of haemoglobin. Beyond that, CO participates in the regulation of apoptosis. CO could be generated from CO-releasing molecules (CORM), such as the tricarbonyl-dichlororuthenium (II) dimer (CORM-2), which is presently considered for the treatment of vascular dysfunction, inflammation, tissue ischaemia and organ rejection. CORM-2 is at least partially effective by modifying gene expression and mitochondrial potential. Erythrocytes lack nuclei and mitochondria but may undergo suicidal cell death or eryptosis, characterized by cell shrinkage and phospholipid scrambling of the cell membrane. Eryptosis is triggered by the increase in cytosolic Ca2+ activity ([ Ca2+ ]i). The present study explored whether CORM-2 influences eryptosis. To this end, [ Ca2+ ]i was estimated from Fluo-3-fluorescence, cell volume from forward scatter, phospholipid scrambling from annexin-V-binding and haemolysis from haemoglobin release. CO-binding haemoglobin (COHb) was estimated utilizing a blood gas analyser. As a result, exposure of erythrocytes for 24 similar to hr to CORM-2 (=5 mu M) significantly increased COHb, [ Ca2+ ]i, forward scatter, annexin-V-binding and haemolysis. Annexin-V-binding was significantly blunted by 100% oxygen and was virtually abolished in the nominal absence of Ca2+ . In conclusion, CORM-2 stimulates cell membrane scrambling of erythrocytes, an effect largely due to Ca2+ entry and partially reversed by O2 .
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