β-carotene inhibits UVA-induced matrix metalloprotease 1 and 10 expression in keratinocytes by a singlet oxygen-dependent mechanism

• Published in: Free radical biology & medicine Vol. 37; no. 5; pp. 654 - 670
• Main Authors: Wertz, Karin, Seifert, Nicole, Hunziker, Petra Buchwald, Riss, Georges, Wyss, Adrian, Lankin, Christopher, Goralczyk, Regina
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.09.2004
• Subjects: Analysis of Variance; Antioxidants - pharmacology; Base Sequence; beta Carotene - pharmacokinetics; beta Carotene - pharmacology; Biological Transport; Cell Line; DNA Primers; Epidermis; Free radicals; Humans; Keratinocytes - drug effects; Keratinocytes - enzymology; Matrix metalloprotease; Matrix Metalloproteinase 1 - drug effects; Matrix Metalloproteinase 1 - genetics; Matrix Metalloproteinase 10; Metalloendopeptidases - drug effects; Metalloendopeptidases - genetics; Oligonucleotide Array Sequence Analysis; Photoprotection; Retinoic acid; Reverse Transcriptase Polymerase Chain Reaction; RNA - genetics; RNA - isolation & purification; Singlet Oxygen - metabolism; Skin aging; Sunlight; Ultraviolet Rays; β-Carotene; UVA; RAR; Free radicals; RARE; 1O 2; δCT; HO-1; Skin aging; RXR; TA; β-Carotene; RA; CT; MMP; THF; Matrix metalloprotease; Photoprotection; Retinoic acid; QRT-PCR
• ISSN: 0891-5849; 1873-4596
• DOI: 10.1016/j.freeradbiomed.2004.05.018

UVA exposure causes skin photoaging by singlet oxygen 1O 2-mediated induction of, e.g., matrix metalloproteases (MMPs). We assessed whether pretreatment with β-carotene, a 1O 2 quencher and retinoic acid (RA) precursor, interferes with UVA-induced gene regulation. HaCaT keratinocytes were precultured with β-carotene at physiological concentrations (0.5, 1.5, and 3.0 μM) prior to exposure to UVA from a Hönle solar simulator (270 kJ/m 2). HaCaT cells accumulated β-carotene in a time- and dose-dependent manner. UVA irradiation massively reduced the cellular β-carotene content. β-Carotene suppressed UVA-induction of MMP-1, MMP-3, and MMP-10, three major matrix metalloproteases involved in photoaging. We show that regulation by not only MMP-1, but also MMP-10, involves 1O 2-dependent mechanisms. β-Carotene dose-dependently quenched 1O 2-mediated induction of MMP-1 and MMP-10. Thus, as in chemical solvent systems, β-carotene quenches 1O 2 also in living cells. Vitamin E did not cooperate with β-carotene to further inhibit MMP induction. HaCaT cells produced weak retinoid activity from β-carotene, as demonstrated by mild upregulation of RARβ and activation of an RARE-dependent reporter gene. β-Carotene did not regulate the genes encoding other RARs, RXRs, or the two β-carotene cleavage enzymes. These results demonstrate that β-carotene acts photoprotectively, and that this effect is mediated by 1O 2 quenching.