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Retinol, at concentrations greater than the physiological limit, induces oxidative stress and apoptosis in human dermal fibroblasts
Author(s) -
Gimeno Amparo,
Zaragozá Rosa,
VivóSesé Inma,
Viña Juan R.,
Miralles Vicente J.
Publication year - 2004
Publication title -
experimental dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.108
H-Index - 96
eISSN - 1600-0625
pISSN - 0906-6705
DOI - 10.1111/j.0906-6705.2004.00112.x
Subject(s) - retinol , oxidative stress , glutathione , retinoic acid , chemistry , lactate dehydrogenase , apoptosis , programmed cell death , lipid peroxidation , vitamin , antioxidant , biochemistry , endocrinology , medicine , biology , enzyme , gene
Abstract: We have investigated the dose (in the range of μM) and time‐dependent effects of four different retinoids (retinol, retinal, retinoic acid and retinol palmitate) on human dermal fibroblasts cultivated in vitro . Retinol and retinal, at a concentration of 20 µM, caused cell damage as evaluated by lactate dehydrogenase activity released into the culture medium. The oxidised glutathione (GSSG)/reduced glutathione (GSH) ratio and malondialdehyde production indicated that 20 µM of retinol provoked oxidative stress in the cultivated human fibroblasts. In the first 8 h after retinol treatment the levels of p53 and Bax proteins as well as caspase 3 activity increased, suggesting apoptotic cell death during the first hours of treatment. If the retinol treatment exceeded 18–24 h we observed necrotic cell death. Vitamin E and coenzyme Q 10 had a protective effect against oxidative stress generated by retinol. Both antioxidant molecules reduced retinol uptake, and in the case of vitamin E the expression of CRABP‐II mRNA was induced, providing a plausible explanation for its protective effect.