Beta-carotene inhibits UVA-induced matrix metalloprotease 1 and 10 expression in keratinocytes by a singlet oxygen-dependent mechanism.
UVA exposure causes skin photoaging by singlet oxygen (1)O(2)-mediated induction of, e.g., matrix metalloproteases (MMPs). We assessed whether pretreatment with beta-carotene, a (1)O(2) quencher and retinoic acid (RA) precursor, interferes with UVA-induced gene regulation. HaCaT keratinocytes were precultured with beta-carotene at physiological concentrations (0.5, 1.5, and 3.0 microM) prior to exposure to UVA from a Hönle solar simulator (270 kJ/m(2)). HaCaT cells accumulated beta-carotene in a time- and dose-dependent manner. UVA irradiation massively reduced the cellular beta-carotene content. Beta-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 (1)O(2)-dependent mechanisms. Beta-carotene dose-dependently quenched (1)O(2)-mediated induction of MMP-1 and MMP-10. Thus, as in chemical solvent systems, beta-carotene quenches (1)O(2) also in living cells. Vitamin E did not cooperate with beta-carotene to further inhibit MMP induction. HaCaT cells produced weak retinoid activity from beta-carotene, as demonstrated by mild upregulation of RAR beta and activation of an RARE-dependent reporter gene. Beta-carotene did not regulate the genes encoding other RARs, RXRs, or the two beta-carotene cleavage enzymes. These results demonstrate that beta-carotene acts photoprotectively, and that this effect is mediated by (1)O(2) quenching.
Wertz
Karin
K
Department Human Nutrition and Health, Carotenoid Group, DSM Nutritional Products, Basel, Switzerland.
Seifert
Nicole
N
Hunziker
Petra Buchwald
PB
Riss
Georges
G
Wyss
Adrian
A
Lankin
Christopher
C
Goralczyk
Regina
R
D000704:Analysis of Variance; D000975:Antioxidants / Q000494:pharmacology*; D001483:Base Sequence; D001692:Biological Transport; D002460:Cell Line; D017931:DNA Primers; D004817:Epidermis; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects / Q000201:enzymology*; D020781:Matrix Metalloproteinase 1 / Q000187:drug effects / Q000235:genetics*; D053506:Matrix Metalloproteinase 10; D008666:Metalloendopeptidases / Q000187:drug effects / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D020133:Reverse Transcriptase Polymerase Chain Reaction; D026082:Singlet Oxygen / Q000378:metabolism*; D013472:Sunlight; D014466:Ultraviolet Rays; D019207:beta Carotene / Q000493:pharmacokinetics / Q000494:pharmacology*
D000975:Antioxidants; D017931:DNA Primers; D019207:beta Carotene; D026082:Singlet Oxygen; D012313:RNA; D008666:Metalloendopeptidases; D053506:Matrix Metalloproteinase 10; D020781:Matrix Metalloproteinase 1