Stimulation of erythrocyte cell membrane scrambling by gedunin.

Abstract

BACKGROUND/AIMS:

Gedunin, an inhibitor of heat shock protein HSP90, triggers apoptosis of tumor cells and is thus effective against malignancy. Moreover, the drug has antimalarial potency. In analogy to apoptosis of nucleated cells, erythrocytes may enter suicidal death or eryptosis, which is characterized by cell shrinkage and by phosphatidylserine translocation to the erythrocyte surface. Eryptosis may be triggered by increase of cytosolic Ca(2+)-activity ([Ca(2+)]i). The present study explored whether gedunin stimulates eryptosis.

METHODS:

Forward scatter was determined to estimate cell volume, annexin V binding to identify phosphatidylserine-exposing erythrocytes, hemoglobin release to depict hemolysis, and Fluo3-fluorescence to quantify [Ca(2+)]i.

RESULTS:

A 48 h exposure of human erythrocytes to gedunin significantly increased [Ca(2+)]i (12 µM), significantly decreased forward scatter (24 µM) and significantly increased annexin-V-binding (12 µM). The effect of gedunin (24 µM) on annexin-V-binding was virtually abrogated by removal of extracellular Ca(2+).

CONCLUSION:

Gedunin stimulates suicidal erythrocyte death or eryptosis, an effect mainly if not exclusively due to stimulation of Ca(2+) entry.

• Authors: Adrian Lupescu, Rosi Bissinger, Jamshed Warsi, Kashif Jilani, Florian Lang
• Journal: Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology (Cell Physiol Biochem) Vol. 33 Issue 6 Pg. 1838-48 ( 2014) ISSN: 1421-9778 [Electronic] Germany
• PMID: 24969439 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 S. Karger AG, Basel.

Chemical References

• Ceramides
• Limonins
• Phosphatidylserines
• gedunin
• Calcium

Topics

• Calcium (metabolism)
• Cell Death (drug effects)
• Cell Size (drug effects)
• Ceramides (metabolism)
• Cytosol (drug effects, metabolism)
• Erythrocyte Membrane (drug effects, metabolism)
• Erythrocytes (drug effects, metabolism)
• Flow Cytometry
• Humans
• Limonins (chemistry, pharmacology)
• Molecular Structure
• Phosphatidylserines (metabolism)
• Time Factors