title: 2-deoxy-d-ribose induces apoptosis by inhibiting the synthesis and increasing the efflux of glutathione.
abstract: Oxidative stress is caused by imbalance between the production of reactive oxygen species (ROS) and biological system ability to readily detoxify the reactive intermediates or repair the resulting damage. 2-deoxy-D-ribose (dRib) is known to induce apoptosis by provoking an oxidative stress by depleting glutathione (GSH). In this paper, we elucidate the mechanisms underlying GSH depletion in response to dRib treatment. We demonstrated that the observed GSH depletion is not only due to inhibition of synthesis, by inhibiting gamma-glutamyl-cysteine synthetase, but also due to its increased efflux, by the activity of multidrug resistance associated proteins transporters. We conclude that dRib interferes with GSH homeostasis and that likely cellular oxidative stress is a consequence of GSH depletion. Various GSH fates, such as direct oxidation, lack of synthesis or of storage, characterize different kinds of oxidative stress. In the light of our observations we conclude that dRib does not induce GSH oxidation but interferes with GSH synthesis and storage. Lack of GSH allows accumulation of ROS and cells, disarmed against oxidative insults, undergo apoptosis.
authors.affiliation: Institute of Genetics and Biophysics Adriano Buzzati Traverso, CNR, Via Pietro Castellino 111, 80131 Napoli, Italy.
authors.forename: Annalisa
authors.initials: A
authors.lastname: Fico
authors.forename: Genesia
authors.initials: G
authors.lastname: Manganelli
authors.forename: Luisa
authors.initials: L
authors.lastname: Cigliano
authors.forename: Paolo
authors.initials: P
authors.lastname: Bergamo
authors.forename: Paolo
authors.initials: P
authors.lastname: Abrescia
authors.forename: Claudio
authors.initials: C
authors.lastname: Franceschi
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Martini
authors.forename: Stefania
authors.initials: S
authors.lastname: Filosa
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D015153:Blotting, Western; D002460:Cell Line; D002855:Chromatography, Thin Layer; D003855:Deoxyribose / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism*; D051379:Mice; D018384:Oxidative Stress / Q000502:physiology*
chemical_list: D003855:Deoxyribose; D005978:Glutathione