These authors equally contributed to this work.
Protective Properties of Novel S-Acyl-Glutathione Thioesters Against Ultraviolet-induced Oxidative Stress
Article first published online: 1 OCT 2012
© 2012 Wiley Periodicals, Inc. Photochemistry and Photobiology © 2012 The American Society of Photobiology
Photochemistry and Photobiology
Volume 89, Issue 2, pages 442–452, March/April 2013
How to Cite
Wright, D., Zampagni, M., Evangelisti, E., Conti, S., D'Adamio, G., Goti, A., Becatti, M., Fiorillo, C., Taddei, N., Cecchi, C. and Liguri, G. (2013), Protective Properties of Novel S-Acyl-Glutathione Thioesters Against Ultraviolet-induced Oxidative Stress. Photochemistry and Photobiology, 89: 442–452. doi: 10.1111/j.1751-1097.2012.01231.x
- Issue published online: 1 MAR 2013
- Article first published online: 1 OCT 2012
- Accepted manuscript online: 30 AUG 2012 11:33AM EST
- Manuscript Accepted: 23 AUG 2012
- Manuscript Received: 9 MAY 2012
- Italian MIUR. Grant Number: PRIN2008R25HBW
UV-induced toxicity is characterized by marked oxidative stress, accompanied by the depletion of key cellular antioxidants, particularly glutathione (GSH). Replenishing cellular GSH may represent a means of counteracting UV-induced toxicity: however, treatment with free GSH is not therapeutically effective due to its unfavorable pharmacokinetic properties. In this study, we show that S-acyl-glutathione (acyl-SG) derivatives, which consist of an acyl chain (of variable length and saturation) linked via a thioester bond to GSH, increase intracellular levels of reduced GSH in primary skin fibroblasts, adenocarcinoma HeLa and neuroblastoma SH-SY5Y cells. Consistent with this, acyl-SG derivatives protect against UV-induced reactive oxygen species (ROS) production and UV-B/C-mediated lipid peroxidation and caspase-3 activation in the analyzed cell lines, with unsaturated thioesters displaying a significantly greater protective effect. Taken together, our findings suggest that acyl-SG thioesters may be therapeutically effective in the treatment of UV-related skin disorders and oxidative stress-mediated conditions in general.