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Salvatrice Calabrò Kousi Alzoubi Rosi Bissinger Kashif Jilani Caterina Faggio Florian Lang 《Basic & clinical pharmacology & toxicology》2015,116(6):460-467
Juglone, a quinone isolated from Juglans mandshurica Maxim, has previously been shown to be effective against malignancy. The effect is at least partially due to stimulation of suicidal death or apoptosis of tumour cells. On the other hand, juglone has been shown to counteract apoptosis, for example, of neurons. In analogy to apoptosis of nucleated cells, erythrocytes may enter eryptosis, a suicidal death characterized by cell shrinkage and breakdown of phosphatidylserine asymmetry of the cell membrane with phosphatidylserine exposure at the erythrocyte surface. Stimulators of eryptosis include increase in cytosolic Ca2+ activity [(Ca2+)i]. This study explored whether juglone stimulates eryptosis. To this end, erythrocyte volume was estimated from forward scatter, phosphatidylserine exposure at the erythrocyte surface from FITC annexin V binding, ceramide abundance from binding of fluorescent antibodies in flow cytometry and cytosolic ATP with a luciferin–luciferase‐based assay. As a result, a 24‐hr exposure of human erythrocytes to juglone (5 μM) significantly decreased erythrocyte forward scatter. Juglone (1–5 μM) significantly increased the percentage of annexin V binding cells. Juglone (5 μM) significantly increased ceramide abundance at the erythrocyte surface and decreased erythrocyte ATP concentration. The effect of juglone (10 μM) on annexin V binding was slightly but significantly blunted by removal of extracellular Ca2+ and by addition of protein kinase C (PKC) inhibitor staurosporine (1 μM). In conclusion, juglone stimulates suicidal erythrocyte death or eryptosis at least in part by upregulation of ceramide abundance, energy depletion and activation of PKC. 相似文献
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Kousi Alzoubi Jasmin Egler Marilena Briglia Antonella Fazio Caterina Faggio Florian Lang 《Toxins》2015,7(8):2822-2834
The natural phosphoprotein phosphatase inhibitor cantharidin, primarily used for topical treatment of warts, has later been shown to trigger tumor cell apoptosis and is thus considered for the treatment of malignancy. Similar to apoptosis of tumor cells, erythrocytes may undergo eryptosis, a suicidal cell death characterized by cell shrinkage and translocation of cell membrane phosphatidylserine to the erythrocyte surface. Signaling of eryptosis includes increase of cytosolic Ca2+-activity ([Ca2+]i), ceramide, oxidative stress and dysregulation of several kinases. Phosphatidylserine abundance at the erythrocyte surface was quantified utilizing annexin-V-binding, cell volume from forward scatter, [Ca2+]i from Fluo3-fluorescence, ceramide from antibody binding, and reactive oxidant species (ROS) from 2′,7′-dichlorodihydrofluorescein diacetate (DCFDA) fluorescence. A 48 h treatment of human erythrocytes with cantharidin significantly increased the percentage of annexin-V-binding cells (≥10 μg/mL), significantly decreased forward scatter (≥25 μg/mL), significantly increased [Ca2+]i (≥25 μg/mL), but did not significantly modify ceramide abundance or ROS. The up-regulation of annexin-V-binding following cantharidin treatment was not significantly blunted by removal of extracellular Ca2+ but was abolished by kinase inhibitor staurosporine (1 μM) and slightly decreased by p38 inhibitor skepinone (2 μM). Exposure of erythrocytes to cantharidin triggers suicidal erythrocyte death with erythrocyte shrinkage and erythrocyte membrane scrambling, an effect sensitive to kinase inhibitors staurosporine and skepinone. 相似文献
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Omar Aljanadi Kousi Alzoubi Rosi Bissinger Florian Lang 《Basic & clinical pharmacology & toxicology》2015,117(6):369-374
The 1,4‐naphthoquinone derivative naphthazarin may trigger apoptosis and is thus considered for the treatment of malignancy. On the other hand, naphthazarin decreases neurotoxicity. In analogy to apoptosis of nucleated cells, erythrocytes may enter eryptosis, the suicidal erythrocyte death characterized by cell shrinkage and by cell membrane scrambling with translocation of phosphatidylserine to the erythrocyte surface. Signalling leading to triggering of eryptosis include increase in cytosolic Ca2+‐activity ([Ca2+]i), ceramide and oxidative stress. The present study explored whether naphthazarin impacts on eryptosis and, if so, to unravel underlying mechanisms. To this end, erythrocyte volume was estimated from forward scatter, phosphatidylserine abundance at the erythrocyte surface from FITC‐annexin‐V‐binding, [Ca2+]i from Fluo3 fluorescence, reactive oxidant species (ROS) from 2′,7′‐dichlorodihydrofluorescein diacetate (DCFDA) fluorescence and ceramide abundance at the erythrocyte surface from binding of fluorescent antibodies in flow cytometry. As a result, a 24‐hr exposure of human erythrocytes to naphthazarin (10 μm ) significantly decreased erythrocyte forward scatter, significantly increased the percentage of annexin‐V‐binding cells, significantly increased ceramide abundance at the erythrocyte surface and significantly increased ROS. The effect of naphthazarin on annexin‐V‐binding was not significantly blunted by removal of extracellular Ca2+. In conclusion, naphthazarin stimulates eryptosis, an effect at least in part due to oxidative stress and enhanced ceramide abundance at the erythrocyte surface. 相似文献
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Kousi Alzoubi Bassel Alktifan Gergely Oswald Myriam Fezai Majed Abed Florian Lang 《Toxins》2014,6(2):650-664
Background: Lumefantrine, a commonly used antimalarial drug, inhibits hemozoin formation in parasites. Several other antimalarial substances counteract parasitemia by triggering suicidal death or eryptosis of infected erythrocytes. Eryptosis is characterized by cell shrinkage and cell membrane scrambling leading to phosphatidylserine-exposure at the erythrocyte surface. Signaling involved in eryptosis include increase of cytosolic Ca2+-activity ([Ca2+]i), formation of ceramide, oxidative stress and/or activation of p38 kinase, protein kinase C (PKC), or caspases. The present study explored, whether lumefantrine stimulates eryptosis. Methods: Cell volume has been estimated from forward scatter, phosphatidylserine-exposure from annexin V binding, [Ca2+]i from Fluo3-fluorescence, reactive oxygen species from 2'',7''-dichlorodihydrofluorescein-diacetate fluorescence, content of reduced glutathione (GSH) from mercury orange fluorescence, and ceramide abundance from binding of fluorescent antibodies in flow cytometry. Results: A 48 h exposure to lumefantrine (3 µg/mL) was followed by a significant increase of annexin-V-binding without significantly altering forward scatter, [Ca2+]i, ROS formation, reduced GSH, or ceramide abundance. The annexin-V-binding following lumefantrine treatment was not significantly modified by p38 kinase inhibitors SB203580 (2 μM) and p38 Inh III (1 μM), PKC inhibitor staurosporine (1 µM) or pancaspase inhibitor zVAD (1 or 10 µM). Conclusions: Lumefantrine triggers cell membrane scrambling, an effect independent from entry of extracellular Ca2+, ceramide formation, ROS formation, glutathione content, p38 kinase, PKC or caspases. 相似文献
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Dimitrios I. Zafeiriou MD PhD Afroditi A. Kousi MD PhD Chaido T. Tsantali MD PhD Eleftherios E. Kontopoulos MD PhD Persa A. Augoustidou-Savvopoulou MD PhD Panagiotis D. Tsoubaris MD PhD Miranta A. Athanasiou MD PhD 《Pediatric neurology》1998,18(5):420-424
Forty patients with beta-thalassemia major (BTM), between 11 and 19 years of age and maintained on long-term desferrioxamine (DFO) treatment, were examined by evoked potential and nerve conduction velocity studies to investigate a possible involvement of the auditory, visual, somatosensory, or peripheral nervous pathways. Pathologic findings in brainstem auditory-, visual-, and somatosensory-evoked potentials, and nerve conduction velocity studies were demonstrated in 25%, 15%, 7.5%, and 25% of the patients, respectively, whereas 15% demonstrated involvement of multiple neural pathways. Subclinical involvement of the auditory pathway was statistically associated with higher mean daily DFO dose and longer duration of DFO therapy, whereas abnormalities regarding the somatosensory pathways were related to older age, longer mean duration of DFO therapy, and lower serum copper levels. Involvement of the peripheral nervous system was related to lower serum copper levels. Multiple involvement of neural pathways was related to longer mean duration of DFO therapy. We conclude that risk factors related to long-term DFO treatment are only partly responsible for the subclinical involvement of neural pathways demonstrated in beta-thalassemia major patients. 相似文献
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Rosalia‐Maria Valeri M.D. Ph.D. Rodoula Kotakidou M.D. Ph.D. Konstantinos Michalakis M.D. Charalambos Andreadis M.D. Ph.D. Kokkona Kousi‐Koliakou M.D. Ph.D. Charikleia Destouni M.D. Ph.D. 《Diagnostic cytopathology》2011,39(5):368-372
Leydig cell tumors (LCT) are rare sex cord‐stromal tumors that account for 2–3% of all testicular tumors. Approximately 10% of LCTs shows evidence of malignant behavior. We present a case of LCT with severe atypia diagnosed by fine‐needle aspiration (FNA) in a 49‐year‐old man who presented with gynecomastia and right testis enlargement. The FNA material on conventional and ThinPrep smears revealed a hemorrhagic and necrotic background with high cellularity, consisting of large cells, isolated or in small cohesive clusters, abundant, eosinophilic cytoplasm, round nuclei, fine chromatin, and variably conspicuous nucleoli. Occasionally, pleomorphic cells with hyperchromatic nuclei and prominent nucleoli were seen. Immunocytochemistry was positive against vimentin, inhibin, and calretinin. Histological examination of the surgical specimen was in accordance with the FNA findings. The cytologic diagnosis of LCT of the testis, using FNA, is achievable in a preoperative setting to vitiate the need for more invasive biopsy procedures; malignancy could be considered on cytology when necrosis and marked atypia are evident. Diagn. Cytopathol. 2011. © 2010 Wiley‐Liss, Inc. 相似文献
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Meletios Kanakis Dimitrios Bobos George Samanidis Nikolaos Papakonstantinou Theophili Kousi Achilleas Lioulias Nicholas Giannopoulos 《Clinical Case Reports》2021,9(7)
Diagnosis of retroaortic left innominate vein is usually made by echocardiography, computed tomography, and magnetic resonance imaging, but in several cases, diagnosis is made in the theater. 相似文献
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