Induction of Suicidal Erythrocyte Death by Nelfinavir
| Autor: | Sabrina Waibel, Rosi Bissinger, Florian Lang |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Programmed cell death
phosphatidylserine Erythrocytes Health Toxicology and Mutagenesis Cell malaria lcsh:Medicine Parasitemia Phosphatidylserines Biology Pharmacology Toxicology medicine.disease_cause Hemolysis Article chemistry.chemical_compound Annexin eryptosis medicine Extracellular Humans oxidative stress Cells Cultured cell volume Nelfinavir calcium Cell Death lcsh:R ROS Phosphatidylserine HIV Protease Inhibitors medicine.disease medicine.anatomical_structure chemistry Immunology Oxidative stress medicine.drug |
| Zdroj: | Toxins, Vol 7, Iss 5, Pp 1616-1628 (2015) Toxins Volume 7 Issue 5 Pages 1616-1628 |
| ISSN: | 2072-6651 |
| Popis: | The HIV protease inhibitor, nelfinavir, primarily used for the treatment of HIV infections, has later been shown to be effective in various infectious diseases including malaria. Nelfinavir may trigger mitochondria-independent cell death. Erythrocytes may undergo eryptosis, a mitochondria-independent suicidal cell death characterized by cell shrinkage and phosphatidylserine translocation to the erythrocyte surface. Triggers of eryptosis include oxidative stress and increase of cytosolic Ca2+-activity ([Ca2+]i). During malaria, accelerated death of infected erythrocytes may decrease parasitemia and thus favorably influence the clinical course of the disease. In the present study, phosphatidylserine abundance at the cell surface was estimated from annexin V binding, cell volume from forward scatter, reactive oxidant species (ROS) from 2',7'-dichlorodihydrofluorescein diacetate (DCFDA) fluorescence, and [Ca2+]i from Fluo3-fluorescence. A 48 h treatment of human erythrocytes with nelfinavir significantly increased the percentage of annexin-V-binding cells (≥5µg/mL), significantly decreased forward scatter (≥2.5µg/mL), significantly increased ROS abundance (10 µg/mL), and significantly increased [Ca2+]i (≥5 µg/mL). The up-regulation of annexin-V-binding following nelfinavir treatment was significantly blunted, but not abolished by either addition of the antioxidant N-acetylcysteine (1 mM) or removal of extracellular Ca2+. In conclusion, exposure of erythrocytes to nelfinavir induces oxidative stress and Ca2+ entry, thus leading to suicidal erythrocyte death characterized by erythrocyte shrinkage and erythrocyte membrane scrambling. |
| Databáze: | OpenAIRE |
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