Reactive oxygen and nitrogen species are involved in sorbitol-induced apoptosis of human erithroleukaemia cells K562 |
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| Authors: | Katia Aquilano Giuseppe Filomeni Livia di Renzo Maura di Vito Carla di Stefano Paola Sinibaldi Salimei |
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| Affiliation: | 1. Department of Biology, University of Rome “Tor Vergata”, Via della Ricerca Scientifica, 00133, Rome, Italy;2. Department of Experimental Medicine, University of Rome “La Sapienza”, Viale Regina Elena 324, 00161, Rome, Italy;3. Department of Experimental Medicine and Biochemical Sciences, University of Rome “Tor Vergata”, Via Montpellier 1, 00133, Rome, Italy |
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| Abstract: | In this study, we found that production of both reactive oxygen (ROS) and nitrogen (RNS) species is a very early event related to treatment with hyperosmotic concentration of sorbitol. The production of nitric oxide (NO) was paralleled by the increase of the mRNA and protein level of the inducible form of the nitric oxide synthase (iNOS). ROS and RNS enhancement, process concomitant to the failure of mitochondrial trans-membrane potential (ΔΨ), was necessary for the induction of apoptosis as demonstrated by the protection against sorbitol-mediated toxicity observed after treatment with ROS scavengers or NOS inhibitors. The synergistic action of ROS and RNS was finally demonstrated by pre-treatment with rosmarinic acid that, by powerfully buffering both these species, prevents impairment of ΔΨ and cell death. Overall results suggest that the occurrence of apoptosis upon sorbitol treatment is an event mediated by oxidative/nitrosative stress rather than a canonical hyperosmotic shock. |
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| Keywords: | Sorbitol ROS RNS mitochondrial transmembrane potential apoptosis rosmarinic acid |
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