Thiols and selenium: protective effect on human skin fibroblasts exposed to UVA radiation.
The sensitivity of human dermal fibroblasts to UVA radiation has been linked to a decrease in intracellular glutathione (GSH) levels. GSH (gamma-glutamyl-cysteinyl-glycine) is a radical scavenger and a cofactor for protective enzymes such as selenium-dependent GSH peroxidases. In this study, we examine the possibility of a cooperative interaction between three cysteine delivery systems and selenium in protecting human cultured fibroblast exposed to UVA radiation. Cells were irradiated (9, 15 and 20 J cm-2) following incubation with N-acetyl-cysteine (NAC, 5 mM), N-acetyl-homocysteine-thiolactone (citiolone (CIT), 1 mM) or L-2-oxothiazolidine-4-carboxylate (OTC, 1 mM). The modulation of the intracellular GSH levels by the addition of the different compounds was determined by enzymatic and separative methods. Cells were harvested for survival analysis by measuring the ability of the cell to adhere and proliferate. Treatments with NAC and CIT resulted in a significant rise in GSH levels compared with control cells, with protection against UVA radiation. OTC did not induce any rise in GSH level; nevertheless, the protective effect afforded by OTC is similar to that observed with NAC and CIT. Moreover, selenium (0.1 mg 1-1), as sodium selenite, significantly increased the protective efficiency of NAC and CIT, but not of OTC. Although the precise mechanism is not known, thiol molecules can inhibit the deleterious effects of UVA radiation. These results provide evidence that compounds capable of inducing GSH synthesis can act with selenium to protect cells against UVA damage.
Emonet
N
N
Service de Dermatologie, Université Joseph Fourier, Grenoble, France.
Leccia
M T
MT
Favier
A
A
Beani
J C
JC
Richard
M J
MJ
D000111:Acetylcysteine / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D002478:Cells, Cultured; D003545:Cysteine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004307:Dose-Response Relationship, Radiation; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000528:radiation effects; D005978:Glutathione / Q000378:metabolism*; D006801:Humans; D011761:Pyrrolidonecarboxylic Acid; D011837:Radiation-Protective Agents; D012867:Skin / Q000166:cytology / Q000187:drug effects / Q000528:radiation effects*; D018038:Sodium Selenite / Q000494:pharmacology*; D013518:Surgery, Plastic; D013844:Thiazoles / Q000494:pharmacology; D053778:Thiazolidines; D013876:Thiophenes / Q000494:pharmacology; D014466:Ultraviolet Rays
D000975:Antioxidants; D011837:Radiation-Protective Agents; D013844:Thiazoles; D053778:Thiazolidines; D013876:Thiophenes; C000486:citiolone; D005978:Glutathione; D018038:Sodium Selenite; D003545:Cysteine; D011761:Pyrrolidonecarboxylic Acid; D000111:Acetylcysteine; C029536:2-oxothiazolidine-4-carboxylic acid