Suicidal erythrocyte death in end-stage renal disease.

Abstract

UNLABELLED:

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 Ca(2+) concentration ([Ca(2+)]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, [Ca(2+)]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 [Ca(2+)]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, [Ca(2+)]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 [Ca(2+)]i, ROS, and ceramide formation.

KEY MESSAGES:

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 Ca(2+) concentration. Eryptosis in uremia is further due to oxidative stress and ceramide formation.

• Authors: Majed Abed, Ferruh Artunc, Kousi Alzoubi, Sabina Honisch, Dorothea Baumann, Michael Föller, Florian Lang
• Journal: Journal of molecular medicine (Berlin, Germany) (J Mol Med (Berl)) Vol. 92 Issue 8 Pg. 871-9 (Aug 2014) ISSN: 1432-1440 [Electronic] Germany
• PMID: 24743961 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Annexin A5
• Ceramides
• Phosphatidylserines
• Reactive Oxygen Species
• Calcium

Topics

• Adult
• Aged
• Aged, 80 and over
• Annexin A5 (metabolism)
• Apoptosis
• Calcium (metabolism)
• Case-Control Studies
• Cell Death
• Ceramides (biosynthesis)
• Erythrocytes (drug effects, metabolism, pathology)
• Female
• Humans
• Intracellular Space (metabolism)
• Kidney Failure, Chronic (diagnosis, etiology, metabolism, pathology, therapy)
• Male
• Middle Aged
• Oxidative Stress
• Phosphatidylserines (pharmacology)
• Reactive Oxygen Species (metabolism)