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 5min toxin exposure. This shift was totally abolished when Na+ and Ca2+ ions were withdrawn from culture medium, whereas cyclosporine-A was ineffective, excluding the occurrence of a controlled biochemical response.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.

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

PELIN, MARCO;SOSA, SILVIO;PACOR, SABRINA;TUBARO, AURELIA;FLORIO, CHIARA
2014

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 5min toxin exposure. This shift was totally abolished when Na+ and Ca2+ 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.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11368/2802126
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