NDLI: Suicidal erythrocyte death in end-stage renal disease

Content Provider	Springer Nature Link
Author	Abed, Majed Artunc, Ferruh Alzoubi, Kousi Honisch, Sabina Baumann, Dorothea Föller, Michael Lang, Florian
Copyright Year	2014
Abstract	Anemia in end-stage renal disease (ESRD) results mainly from erythropoietin and iron deficiency. Anemia could be confounded, however, by accelerated clearance of circulating erythrocytes because of premature suicidal erythrocyte death or eryptosis characterized by phosphatidylserine exposure at the erythrocyte surface. Triggers of eryptosis include increased cytosolic Ca2+ concentration ([Ca2+]i), oxidative stress, and ceramide. The present study explored whether and how ESRD influences eryptosis. Blood was drawn from healthy volunteers (n = 20) as well as ESRD patients (n = 20) prior to and after hemodialysis. Phosphatidylserine exposure was estimated from annexin V binding, [Ca2+]i from Fluo3-fluorescence, reactive oxygen species (ROS) from 2′,7′dichlorodihydrofluorescein fluorescence, and ceramide from fluorescein-isothiocyanate-conjugated antibody binding in flow cytometry. Measurements were made in erythrocytes from freshly drawn blood and in erythrocytes from healthy volunteers exposed in vitro for 24 h to plasma from healthy volunteers or ESRD patients prior to and following dialysis. The patients suffered from anemia (hemoglobin 10.1 ± 0.5 g/100 ml) despite 1.96 ± 0.34 % reticulocytes. The percentage of phosphatidylserine-exposing erythrocytes was significantly higher in ESRD patients (0.84 ± 0.09 %) than in healthy volunteers (0.43 ± 0.04 %) and was significantly increased immediately after dialysis (1.35 ± 0.13 %). The increase in phosphatidylserine exposure was paralleled by increase in [Ca2+]i, oxidative stress, and ceramide abundance. As compared to addition of plasma from healthy individuals, addition of predialytic but not of postdialytic plasma from ESRD patients increased phosphatidylserine exposure, [Ca2+]i, ROS, and ceramide abundance. In conclusion, both, dialyzable components of uremic plasma and dialysis procedure, trigger eryptosis at least in part by increasing erythrocyte [Ca2+]i, ROS, and ceramide formation. Anemia in uremia results in part from eryptosis, the suicidal erythrocyte death. Eryptosis in uremia is triggered in part by a dialyzable plasma component. Eryptosis in uremia is further triggered by dialysis procedure. Eryptosis in uremia is in part due to increased cytosolic Ca2+ concentration. Eryptosis in uremia is further due to oxidative stress and ceramide formation.
Starting Page	871
Ending Page	879
Page Count	9
File Format	PDF
ISSN	09462716
Journal	Journal of Molecular Medicine
Volume Number	92
Issue Number	8
e-ISSN	14321440
Language	English
Publisher	Springer Berlin Heidelberg
Publisher Date	2014-04-18
Publisher Place	Berlin/Heidelberg
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Phosphatidylserine Calcium Eryptosis Oxidative stress Ceramide abundance Anemia Dialysis End-stage renal disease Molecular Medicine Human Genetics Internal Medicine
Content Type	Text
Resource Type	Article
Subject	Drug Discovery Molecular Medicine Genetics (clinical)

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1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
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4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
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