Format

Send to

Choose Destination
See comment in PubMed Commons below
Free Radic Biol Med. 2008 Jul 15;45(2):211-7. doi: 10.1016/j.freeradbiomed.2008.04.017. Epub 2008 Apr 23.

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

Author information

1
Institute of Genetics and Biophysics Adriano Buzzati Traverso, CNR, Via Pietro Castellino 111, 80131 Napoli, Italy.

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.

[Indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science
    Loading ...
    Support Center