The marine toxin palytoxin induces necrotic death in HaCaT cells through a rapid mitochondrial damage.

Abstract

Palytoxin (PLTX) is one of the most toxic algal biotoxin known so far. It transforms the Na(+)/K(+)-ATPase into a cationic channel inducing a massive intracellular Na(+) influx. However, from a mechanistic point of view, the features and the intracellular pathways leading to PLTX-induced cell death are still not completely characterized. This study on skin HaCaT keratinocytes demonstrates that PLTX induces necrosis since propidium iodide uptake was observed already after 1 h toxin exposure, an effect that was not lowered by toxin removal. Furthermore, necrotic-like morphological alterations were evidenced by confocal microscopy. Apoptosis occurrence was excluded since no caspases 3/7, caspase 8, and caspase 9 activation as well as no apoptotic bodies formation were recorded. Necrosis was preceded by a very early mitochondrial damage as indicated by JC-1 fluorescence shift, recorded already after 5 min toxin exposure. This shift was totally abolished when Na(+) and Ca(2+) ions were withdrawn from culture medium, whereas cyclosporine-A was ineffective, excluding the occurrence of a controlled biochemical response. These results clearly establish necrosis as the primary mechanism for PLTX-induced cell death in HaCaT cells. The rapidity of mitochondrial damage and the consequent irreversible necrosis rise serious concerns about the very fast onset of PLTX toxic effects.

• Authors: Marco Pelin, Silvio Sosa, Sabrina Pacor, Aurelia Tubaro, Chiara Florio
• Journal: Toxicology letters (Toxicol Lett) Vol. 229 Issue 3 Pg. 440-50 (Sep 17 2014) ISSN: 1879-3169 [Electronic] Netherlands
• PMID: 25066017 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Acrylamides
• Cnidarian Venoms
• Caspases
• palytoxin

Topics

• Acrylamides (pharmacology)
• Blotting, Western
• Caspases (drug effects, metabolism)
• Cell Death (drug effects)
• Cell Line
• Cell Survival (drug effects)
• Cnidarian Venoms (pharmacology)
• Flow Cytometry
• Humans
• Keratinocytes (drug effects)
• Microscopy, Fluorescence
• Mitochondria (drug effects)