Redox regulation of cellular stress response by ferulic acid ethyl ester in human dermal fibroblasts: role of vitagenes

• Published in: Clinics in dermatology 2008-07, Vol.26 (4), p.358-363
• Main Authors: Calabrese, Vittorio, MD, PhD, Calafato, Stella, MD, Puleo, Eduardo, PhD, Cornelius, Carolin, PhD, Sapienza, Maria, PhD, Morganti, Pierfrancesco, MD, PhD, Mancuso, Cesare, MD, PhD
• Format: Article
• Language: English
• Subjects: Antioxidants - pharmacology; Caffeic Acids - pharmacology; Cells, Cultured; Dermatology; Fibroblasts - metabolism; Heme Oxygenase-1 - metabolism; HSP70 Heat-Shock Proteins - metabolism; Humans; Hydrogen Peroxide - pharmacology; Lipid Peroxidation - drug effects; Oxidative Stress - drug effects; Protein Carbonylation - drug effects; Skin - cytology
• ISSN: 0738-081X; 1879-1131
• DOI: 10.1016/j.clindermatol.2008.01.005

Abstract Skin is one of the main targets for reactive oxygen species; thus, reactive oxygen species-induced damage and protein and lipid modifications occur, and skin can undergo a wide array of diseases, from photosensitivity to cancer. In this study, human dermal fibroblasts exposed to hydrogen peroxide (0–1000 μmol/L) exhibited a marked increase in both protein carbonyls and 4-hydroxy-2-nonenal, which are indices of protein and lipid oxidation, respectively. An amount of 25 μmol/L ferulic acid ethyl ester, a well-known nutritional antioxidant, significantly counteracted both protein and lipid oxidation and reduced the loss in cell viability elicited by 500 μmol/L of hydrogen peroxide. A common way for cells to react to oxidative stress is up-regulation of vitagenes. To the vitagene family belong the heat shock proteins heme oxygenase-1 and heat shock protein-70, which are involved in the cellular defense against oxidative stress by different mechanisms. The administration of 25 μmol/L ferulic acid ethyl ester significantly decreased hydrogen peroxide-induced protein and lipid oxidation. Dermal fibroblasts exposed to 25 μmol/L ferulic acid ethyl ester in the presence of 500 μmol/L hydrogen peroxide showed an increased level of both heme oxygenase-1 and heat shock protein-70 compared with dermal fibroblasts treated with hydrogen peroxide alone. These findings provide evidence for the protective role of vitagenes in free radical-induced skin damage and highlight the potential protective use of nutritional antioxidants, such as ferulic acid and its derivatives.