Triggering of Suicidal Erythrocyte Death by Zosuquidar Article Swipe
Marilena Briglia
,
Antonella Fazio
,
Caterina Faggio
,
Florian Läng
·
YOU?
·
· 2015
· Open Access
·
· DOI: https://doi.org/10.1159/000438589
YOU?
·
· 2015
· Open Access
·
· DOI: https://doi.org/10.1159/000438589
Background: The P-glycoprotein inhibitor zosuquidar (LY335979) is clinically used to augment the effect of cytostatic drugs on suicidal tumor cell death or apoptosis. The present study explored whether the substance is cytotoxic to erythrocytes. Upon injury, erythrocytes may undergo suicidal cell death or eryptosis, which is characterized by cell shrinkage and translocation of cell membrane phosphatidylserine to the erythrocyte surface. Signaling of eryptosis include increase of cytosolic Ca2+-activity ([Ca2+]i), oxidative stress and activation of several kinases, such as p38 kinase and protein kinase C. Methods: Phosphatidylserine abundance at the erythrocyte surface was quantified from binding of FITC-labelled annexin-V, cell volume from forward scatter, [Ca2+]i from Fluo3-fluorescence, and reactive oxygen species (ROS) from 2′,7′-dichlorodihydrofluorescein diacetate (DCFDA) fluorescence. Results: A 48 h treatment of human erythrocytes with zosuquidar significantly increased the percentage of annexin-V-binding cells (2 and 4 µg/ml), significantly decreased forward scatter (4 µg/ml), significantly increased [Ca2+]i (4 µg/ml), but did not significantly modify ROS. The up-regulation of annexin-V-binding following zosuquidar (4 µg/ml) treatment was significantly blunted by removal of extracellular Ca2+, by presence of p38 kinase inhibitor SB203580 (2 µM) and by presence of protein kinase C inhibitor calphostin (100 nM). Conclusions: Exposure of erythrocytes to zosuquidar triggers suicidal erythrocyte death with erythrocyte shrinkage and erythrocyte membrane scrambling, an effect involving Ca2+ entry and requiring activity of SB203580 and calphostin sensitive kinases.
Related Topics
Concepts
Phosphatidylserine
Calphostin C
Kinase
Annexin
Calphostin
Reactive oxygen species
Programmed cell death
Apoptosis
p38 mitogen-activated protein kinases
Cell biology
Oxidative stress
Protein kinase A
Biology
Chemistry
Molecular biology
Biochemistry
Membrane
Phospholipid
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1159/000438589
- https://www.karger.com/Article/Pdf/438589
- OA Status
- gold
- Cited By
- 49
- References
- 94
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W2212262057
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W2212262057Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1159/000438589Digital Object Identifier
- Title
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Triggering of Suicidal Erythrocyte Death by ZosuquidarWork title
- Type
-
articleOpenAlex work type
- Language
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enPrimary language
- Publication year
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2015Year of publication
- Publication date
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2015-01-01Full publication date if available
- Authors
-
Marilena Briglia, Antonella Fazio, Caterina Faggio, Florian LängList of authors in order
- Landing page
-
https://doi.org/10.1159/000438589Publisher landing page
- PDF URL
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https://www.karger.com/Article/Pdf/438589Direct link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
- OA URL
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https://www.karger.com/Article/Pdf/438589Direct OA link when available
- Concepts
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Phosphatidylserine, Calphostin C, Kinase, Annexin, Calphostin, Reactive oxygen species, Programmed cell death, Apoptosis, p38 mitogen-activated protein kinases, Cell biology, Oxidative stress, Protein kinase A, Biology, Chemistry, Molecular biology, Biochemistry, Membrane, PhospholipidTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
49Total citation count in OpenAlex
- Citations by year (recent)
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2024: 1, 2023: 2, 2022: 1, 2021: 1, 2020: 5Per-year citation counts (last 5 years)
- References (count)
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94Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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