title: Protective properties of novel S-acyl-glutathione thioesters against ultraviolet-induced oxidative stress.
abstract: 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.
authors.affiliation: Department of Biochemical Sciences, University of Florence, Firenze, Florence, Italy.
authors.forename: Daniel
authors.initials: D
authors.lastname: Wright
authors.forename: Mariagioia
authors.initials: M
authors.lastname: Zampagni
authors.forename: Elisa
authors.initials: E
authors.lastname: Evangelisti
authors.forename: Simona
authors.initials: S
authors.lastname: Conti
authors.forename: Giampiero
authors.initials: G
authors.lastname: D'Adamio
authors.forename: Andrea
authors.initials: A
authors.lastname: Goti
authors.forename: Matteo
authors.initials: M
authors.lastname: Becatti
authors.forename: Claudia
authors.initials: C
authors.lastname: Fiorillo
authors.forename: Niccolò
authors.initials: N
authors.lastname: Taddei
authors.forename: Cristina
authors.initials: C
authors.lastname: Cecchi
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Liguri
mesh_terms: D000975:Antioxidants / Q000494:pharmacology*; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D004789:Enzyme Activation / Q000187:drug effects; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology / Q000528:radiation effects; D005978:Glutathione / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology*; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects / Q000528:radiation effects; D018384:Oxidative Stress; D061251:Primary Cell Culture; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors; D012867:Skin / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology / Q000528:radiation effects; D014466:Ultraviolet Rays
chemical_list: D000975:Antioxidants; D017382:Reactive Oxygen Species; D053148:Caspase 3; D005978:Glutathione