Geldanamycin-induced phosphatidylserine translocation in the erythrocyte membrane.

Abstract

BACKGROUND/AIMS:

Geldanamycin, a benzoquinone ansamycin antibiotic, and its analogues induce apoptosis of tumor cells and are thus considered for the treatment of cancer. Similar to apoptosis of nucleated cells, erythrocytes may enter eryptosis, the suicidal erythrocyte death characterized by cell shrinkage and by cell membrane scrambling with phosphatidylserine-exposure at the erythrocyte surface. Triggers of eryptosis include increase of cytosolic Ca(2+)-concentration ([Ca(2+)]i) and formation of ceramide. The present study explored, whether geldanamycin modifies [Ca(2+)]i, ceramide formation, cell volume and phosphatidylserine abundance at the erythrocyte surface.

METHODS:

Erythrocyte volume was estimated from forward scatter, phosphatidylserine-abundance from annexin V binding, hemolysis from hemoglobin release, ceramide formation from binding of fluorescent antibodies and [Ca(2+)]i from Fluo3-fluorescence.

RESULTS:

A 48 hours exposure to geldanamycin significantly decreased forward scatter (≥ 5 µM), significantly increased annexin-V-binding (≥ 25 µM), but did not significantly modify Fluo3-fluorescence (up to 50 µM). The annexin-V-binding following geldanamycin treatment was not significantly modified by removal of extracellular Ca(2+) but was paralleled by significantly increased ceramide formation (50 µM).

CONCLUSIONS:

Geldanamycin stinulated eryptosis, an effect at least partially due to ceramide formation.

• Authors: Kashif Jilani, Syed M Qadri, Florian Lang
• Journal: Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology (Cell Physiol Biochem) Vol. 32 Issue 6 Pg. 1600-9 ( 2013) ISSN: 1421-9778 [Electronic] Germany
• PMID: 24335345 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2013 S. Karger AG, Basel.

Chemical References

• Aniline Compounds
• Anti-Bacterial Agents
• Benzoquinones
• Ceramides
• Hemoglobins
• Lactams, Macrocyclic
• Phosphatidylserines
• Xanthenes
• Fluo-3
• Calcium
• geldanamycin

Topics

• Aniline Compounds (chemistry)
• Anti-Bacterial Agents (pharmacology)
• Apoptosis (drug effects)
• Benzoquinones (pharmacology)
• Calcium (metabolism)
• Cell Size (drug effects)
• Ceramides (metabolism)
• Erythrocyte Membrane (metabolism)
• Erythrocytes (cytology, drug effects, metabolism)
• Hemoglobins (metabolism)
• Hemolysis (drug effects)
• Humans
• Lactams, Macrocyclic (pharmacology)
• Phosphatidylserines (metabolism)
• Xanthenes (chemistry)