Next Article in Journal
Aflatoxin Biosynthesis Is a Novel Source of Reactive Oxygen Species—A Potential Redox Signal to Initiate Resistance to Oxidative Stress?
Previous Article in Journal
One Health and Cyanobacteria in Freshwater Systems: Animal Illnesses and Deaths Are Sentinel Events for Human Health Risks
Article Menu

Export Article

Open AccessArticle
Toxins 2015, 7(5), 1396-1410; doi:10.3390/toxins7051396

Enhanced Eryptosis Following Gramicidin Exposure

Department of Physiology, University of Tübingen, Gmelinstr. 5, 72076 Tuebingen, Germany
*
Author to whom correspondence should be addressed.
Academic Editor: John P. Berry
Received: 23 December 2014 / Revised: 25 March 2015 / Accepted: 17 April 2015 / Published: 23 April 2015
View Full-Text   |   Download PDF [560 KB, uploaded 23 April 2015]   |  

Abstract

The peptide antibiotic and ionophore gramicidin has previously been shown to trigger apoptosis of nucleated cells. In analogy to apoptosis, the suicidal death of erythrocytes or eryptosis involves cell shrinkage and cell membrane scrambling with phosphatidylserine translocation to the erythrocyte surface. Triggers of eryptosis include oxidative stress, increase of cytosolic Ca2+ activity ([Ca2+]i), and ceramide. The present study explored, whether gramicidin triggers eryptosis. To this end phosphatidylserine exposure at the cell surface was estimated from annexin V binding, cell volume from forward scatter, red blood cell distribution width (RDW) from electronic particle counting, reactive oxidant species (ROS) from 2',7'-dichlorodihydrofluorescein diacetate (DCFDA) fluorescence, [Ca2+]i from Fluo3- and Fluo4 fluorescence, and ceramide abundance from binding of specific antibodies. As a result, a 24 h exposure of human erythrocytes to gramicidin significantly increased the percentage of annexin-V-binding cells (≥1 µg/mL), forward scatter (≥0.5 µg/mL) and hemolysis. Gramicidin enhanced ROS activity, [Ca2+]i and ceramide abundance at the erythrocyte surface. The stimulation of annexin-V-binding by gramicidin was significantly blunted but not abolished by removal of extracellular Ca2+. In conclusion, gramicidin stimulates phospholipid scrambling of the erythrocyte cell membrane, an effect at least partially due to induction of oxidative stress, increase of [Ca2+]i and up-regulation of ceramide abundance. Despite increase of [Ca2+]i, gramicidin increases cell volume and slightly reduces RWD. View Full-Text
Keywords: phosphatidylserine; gramicidin; calcium; cell volume; ROS; oxidative stress; eryptosis phosphatidylserine; gramicidin; calcium; cell volume; ROS; oxidative stress; eryptosis
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

Malik, A.; Bissinger, R.; Liu, G.; Liu, G.; Lang, F. Enhanced Eryptosis Following Gramicidin Exposure. Toxins 2015, 7, 1396-1410.

Show more citation formats Show less citations formats

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Toxins EISSN 2072-6651 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top