The marine toxin palytoxin induces necrotic death in HaCaT cells through a rapid mitochondrial damage |
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Authors: | Marco Pelin Silvio Sosa Sabrina Pacor Aurelia Tubaro Chiara Florio |
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Affiliation: | Department of Life Science, University of Trieste, Via Valerio 6, 34127 Trieste, Italy |
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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 This shift was totally abolished when Na+ and Ca2+ ions were withdrawn from culture medium, whereas cyclosporine-A was ineffective, excluding the occurrence of a controlled biochemical response. |
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Keywords: | BNIP3, Bcl-2/adenovirus E1B 19-kilodalton interacting protein LDH, lactic dehydrogenase DAPI, 4&prime ,6-diamidino-2-phenylindole DIL, 1,1&prime -dioctadecyl-3,3,3&prime ,3&prime -tetramethylindocarbocyanine perchlorate DMA, 5-(N,N-dimethyl) amiloride ENaC, epithelial Na+ channel MFI, mean fluorescence intensity MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide MPTPs, mitochondrial permeability transition pores PI, propidium iodide PBS, phosphate buffer saline PLTX, palytoxin PFA, paraformaldehyde NHE, Na+/H+ exchanger ROS, reactive oxygen species TTBS, tween/tris-buffered salt solution |
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