β-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 (1O2)-dependent pathways. Using microarrays, we assessed whether pre-treatment with the 1O2 quencher β-carotene (βC; 1.5 μM) 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, βC 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 βC/UVA interaction involved multiple mechanisms. In unirradiated keratinocytes, gene regulations suggest that βC reduced stress signals and extracellular matrix (ECM) degradation, and promoted keratinocyte differentiation. In irradiated cells, expression profiles indicate that βC inhibited UVA-induced ECM degradation, and enhanced UVA induction of tanning-associated protease-activated receptor 2. Combination of βC-promoted keratinocyte differentiation with the cellular “UV response” caused synergistic induction of cell cycle arrest and apoptosis. In conclusion, βC at physiological concentrations interacted with UVA effects in keratinocytes by mechanisms that included, but were not restricted to 1O2 quenching. The retinoid effect of βC was minor, indicating that the βC effects reported here were predominantly mediated through vitamin A-independent pathways.