beta-Carotene interferes with ultraviolet light A-induced gene expression by multiple pathways.
Ultraviolet light A (UVA) exposure is thought to cause skin aging mainly by singlet oxygen ((1)O(2))-dependent pathways. Using microarrays, we assessed whether pre-treatment with the (1)O(2) quencher beta-carotene (betaC; 1.5 microM) prevents UVA-induced gene regulation in HaCaT human keratinocytes. Downregulation of growth factor signaling, moderate induction of proinflammatory genes, upregulation of immediate early genes including apoptotic regulators and suppression of cell cycle genes were hallmarks of the UVA effect. Of the 568 UVA-regulated genes, betaC reduced the UVA effect for 143, enhanced it for 180, and did not interact with UVA for 245 genes. The different interaction modes imply that betaC/UVA interaction involved multiple mechanisms. In unirradiated keratinocytes, gene regulations suggest that betaC reduced stress signals and extracellular matrix (ECM) degradation, and promoted keratinocyte differentiation. In irradiated cells, expression profiles indicate that betaC inhibited UVA-induced ECM degradation, and enhanced UVA induction of tanning-associated protease-activated receptor 2. Combination of betaC-promoted keratinocyte differentiation with the cellular "UV response" caused synergistic induction of cell cycle arrest and apoptosis. In conclusion, betaC at physiological concentrations interacted with UVA effects in keratinocytes by mechanisms that included, but were not restricted to (1)O(2) quenching. The retinoid effect of betaC was minor, indicating that the betaC effects reported here were predominantly mediated through vitamin A-independent pathways.
Wertz
Karin
K
DSM Nutritional Products, 205/217A, PO Box 3255, Department of Human Nutrition and Health, CH-4002 Basel, Switzerland. karin.wertz@dsm.com
Hunziker
Petra Buchwald
PB
Seifert
Nicole
N
Riss
Georges
G
Neeb
Martin
M
Steiner
Guido
G
Hunziker
Willi
W
Goralczyk
Regina
R
D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D002454:Cell Differentiation / Q000187:drug effects / Q000528:radiation effects; D002478:Cells, Cultured; D015870:Gene Expression / Q000187:drug effects / Q000276:immunology / Q000528:radiation effects; D006801:Humans; D007155:Immunologic Factors / Q000235:genetics; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects* / Q000528:radiation effects*; D053506:Matrix Metalloproteinase 10; D008666:Metalloendopeptidases / Q000235:genetics; D011480:Protease Inhibitors / Q000378:metabolism; D044464:Receptor, PAR-2 / Q000235:genetics; D014212:Tretinoin / Q000378:metabolism; D014466:Ultraviolet Rays; D019207:beta Carotene / Q000494:pharmacology*
D000975:Antioxidants; D007155:Immunologic Factors; D011480:Protease Inhibitors; D044464:Receptor, PAR-2; D019207:beta Carotene; D014212:Tretinoin; D008666:Metalloendopeptidases; D053506:Matrix Metalloproteinase 10