title: Vitamin C derivative ascorbyl palmitate promotes ultraviolet-B-induced lipid peroxidation and cytotoxicity in keratinocytes.
abstract: Among the preventative and protective strategies against the harmful effects of ultraviolet radiation to the skin is the application of antioxidants. Ascorbic acid has been shown to protect against sunburn, delay the onset of skin tumors, and reduce ultraviolet-B-radiation-induced skin wrinkling. In this work, we sought to determine the antioxidative properties of a lipid-soluble derivative of ascorbic acid, ascorbic acid-6-palmitate. We found that ascorbic acid-6-palmitate reduced cellular levels of reactive oxygen species following ultraviolet B irradiation. Treatment of keratinocytes with ascorbic acid-6-palmitate inhibited ultraviolet-B-mediated activation of epidermal growth factor receptor, extracellular regulated kinases 1 and 2, and p38 kinase because of its ability to prevent reduced glutathione depletion and scavenge hydrogen peroxide. Ascorbic acid-6-palmitate strongly promoted ultraviolet-B-induced lipid peroxidation, c-Jun N-terminal kinase activation, and cytotoxicity, however. End products of lipid peroxidation, such as 4-hydroxy-2-nonenal, have been reported to mediate stress-activated protein kinase activation and cell toxicity in epithelial cells. The lipid component of ascorbic acid-6-palmitate probably contributes to the generation of oxidized lipid metabolites that are toxic to epidermal cells. Our data suggest that, despite its antioxidant properties, ascorbic acid-6-palmitate may intensify skin damage following physiologic doses of ultraviolet radiation.
authors.affiliation: Department of Dermatology, Mayo Clinic, Rochester, Minnesota 55905, USA.
authors.forename: Alexander
authors.initials: A
authors.lastname: Meves
authors.forename: Sibylle N
authors.initials: SN
authors.lastname: Stock
authors.forename: Astrid
authors.initials: A
authors.lastname: Beyerle
authors.forename: Mark R
authors.initials: MR
authors.lastname: Pittelkow
authors.forename: Dominik
authors.initials: D
authors.lastname: Peus
mesh_terms: D000975:Antioxidants / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology*; D066246:ErbB Receptors / Q000378:metabolism; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D050356:Lipid Metabolism; D015227:Lipid Peroxidation / Q000187:drug effects / Q000528:radiation effects; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000528:radiation effects; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D014466:Ultraviolet Rays; D048051:p38 Mitogen-Activated Protein Kinases
chemical_list: D000975:Antioxidants; D017382:Reactive Oxygen Species; D066246:ErbB Receptors; D048031:JNK Mitogen-Activated Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D001205:Ascorbic Acid; C031226:6-O-palmitoylascorbic acid