Differential regulation of Cu, Zn- and Mn-superoxide dismutases by retinoic acid in normal and psoriatic human fibroblasts.
Superoxide dismutases' (SODs) expression is altered in several diseases including Alzheimer, atherosclerosis, cancer and psoriasis. Previously, we reported a marked increase in Mn-SOD and Cu,Zn-SOD functional activity in human dermal psoriatic fibroblasts. As retinoic acid (RA) has been used in the treatment of psoriasis and a mechanism for its beneficial effects is not understood, we investigated the effects of RA on SOD mRNA and protein expression levels in human normal and psoriatic fibroblasts. Prior to RA exposure, Cu,Zn-SOD protein and mRNA levels were similar in normal compared to psoriatic fibroblasts while Mn-SOD protein and mRNA levels were increased in psoriatic cells. However, in contrast to normal fibroblasts, exposure of psoriatic fibroblasts to 1 microM RA down-regulated Mn-SOD mRNA, and also decreased Mn-SOD activity by approximately 80% with no change in Mn-SOD protein levels. In contrast, Cu,Zn-SOD protein and enzymatic activity were modestly reduced by RA treatment in both normal and psoriatic fibroblasts. Furthermore, RA treatment of psoriatic fibroblasts also caused a decrease in Cu,Zn-SOD steady-state mRNA levels. These results indicate that RA can serve as a regulatory agent to down-regulate the steady-state levels of both Mn-SOD and Cu,Zn-SOD in psoriatic cells. These findings offer a new model for the antiinflammatory activity of RA when used in the treatment of psoriasis.
Gerbaud
Pascale
P
INSERM U 427, Faculté des Sciences Pharmaceutiques et Biologiques de Paris, Université René Descartes, Paris V, 4 avenue de l'Observatoire, 75270 Paris Cedex 06, France.
Petzold
Loïc
L
Thérond
Patrice
P
Anderson
Wayne B
WB
Evain-Brion
Danièle
D
Raynaud
Françoise
F
D015535:Arthritis, Psoriatic / Q000201:enzymology* / Q000235:genetics; D002478:Cells, Cultured; D005260:Female; D005347:Fibroblasts; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D008297:Male; D020871:RNA Stability / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D014212:Tretinoin / Q000494:pharmacology*
D012333:RNA, Messenger; D014212:Tretinoin; D013482:Superoxide Dismutase