Modulation of UVA-induced lipid peroxidation and suppression of UVB-induced ornithine decarboxylase response by all-trans-retinoic acid in human skin fibroblasts in vitro.
Although clinical evidence of improvement of human skin photodamage by all-trans-retinoic acid (atRA) has accumulated, evidence for its preventative effects against photodamage is limited. Here we studied human skin fibroblasts in vitro. For determination of atRA uptake and metabolism, cells were treated with 3 or 10 microM atRA and retinoids analyzed by HPLC. After 16h a peak of cellular retinoid levels was reached, mainly atRA and 13-cis-RA. At this time point cells were irradiated with UVA (1-20 J/cm2) or UVB (5-500 mJ/cm2). TBARS in medium supernatant were used as an indicator of lipid peroxidation; ornithine decarboxylase (ODC) activity served as a marker of the mutagenic and carcinogenic effects of UV light. 1 h post irradiation (p.i.) with 20 J/cm2 UVA, TBARS production was enhanced by a 3 microM atRA treatment (121+/-5% of vehicle treated cells) and decreased by a 10 microM atRA treatment (75+/-2% of vehicle treated cells), and not significantly altered in UVB irradiated cells. 24 h p.i. with 50 mJ/cm2 UVB, ODC activity peaked in vehicle treated cells at a 7.4+/-0.2-fold increase compared to sham irradiated control cells, and was reduced to a 4.9+/-0.2-fold increase by 3 microM atRA. Treatment with 10 microM atRA further decreased ODC activity (3.7+/-1.0-fold increase) and this delayed activity peak occurred at 36 h p.i. ODC activity was not significantly enhanced by UVA irradiation. These results suggest that in normal human skins fibroblast atRA and/or its metabolites influence the UVA-induced lipid peroxidation by at least two distinct antagonistic mechanisms, while the ODC response to UVB-induced DNA damage possibly involves a ROS-independent, retinoid-sensitive regulatory pathway.
Francz
P I
PI
Institut für Biologische Chemie und Ernährungswissenschaft, Universität Hohenheim, Stuttgart, Germany.
Conrad
J
J
Biesalski
H K
HK
D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D004790:Enzyme Induction; D005347:Fibroblasts / Q000187:drug effects / Q000201:enzymology / Q000528:radiation effects; D006801:Humans; D015227:Lipid Peroxidation / Q000528:radiation effects*; D008297:Male; D009955:Ornithine Decarboxylase / Q000096:biosynthesis*; D012867:Skin / Q000187:drug effects* / Q000201:enzymology / Q000528:radiation effects*; D014212:Tretinoin / Q000494:pharmacology*; D014466:Ultraviolet Rays
D014212:Tretinoin; D009955:Ornithine Decarboxylase