Reactive oxygen and nitrogen species are involved in sorbitol-induced apoptosis of human erithroleukaemia cells K562.
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 (DeltaPsi), 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 DeltaPsi 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.
Aquilano
Katia
K
Department of Biology, University of Rome "Tor Vergata", Via della Ricerca Scientifica, Rome 00133, Italy.
Filomeni
Giuseppe
G
Di Renzo
Livia
L
Vito
Maura di
Md
Stefano
Carla di
Cd
Salimei
Paola Sinibaldi
PS
Ciriolo
Maria R
MR
Marfè
Gabriella
G
D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis; D045744:Cell Line, Tumor; D002470:Cell Survival; D002934:Cinnamates / Q000494:pharmacology; D053938:DNA Fragmentation; D053630:Depsides / Q000494:pharmacology; D006801:Humans; D020014:K562 Cells; D007938:Leukemia / Q000473:pathology*; D008564:Membrane Potentials; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D013012:Sorbitol / Q000494:pharmacology*; D013997:Time Factors; D000097123:Rosmarinic Acid
D000975:Antioxidants; D002934:Cinnamates; D053630:Depsides; D052247:Nitric Oxide Synthase Type II; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D013012:Sorbitol; D000097123:Rosmarinic Acid