2-deoxy-d-ribose induces apoptosis by inhibiting the synthesis and increasing the efflux of glutathione

Annalisa Fico, Genesia Manganelli, Luisa Cigliano, Paolo Bergamo, Paolo Abrescia, Claudio Franceschi, Giuseppe Martini, Stefania Filosa

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)211-217
Number of pages7
JournalFree Radical Biology and Medicine
Volume45
Issue number2
DOIs
Publication statusPublished - Jul 15 2008

Keywords

  • dRib
  • Embryonic stem cells
  • G6PD
  • GSH
  • Oxidative stress

ASJC Scopus subject areas

  • Medicine(all)
  • Toxicology
  • Clinical Biochemistry

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