Beta-Carotene Interference With Uva-Induced Gene Expression By Multiple Pathways

UVA exposure causes skin photoaging by singlet oxygen (O-1(2))-mediated induction of matrix metalloproteases (MMPs). We assessed whether beta-carotene, a carotenoid known as O-1(2) quencher and retinoic acid (RA) precursor, interferes with UVA-induced gene regulation and prevents UVA-induced gene regulation in HaCaT human keratinocytes. HaCaT cells accumulated beta-carotene in a time- and dose-dependent manner. UVA irradiation massively reduced the cellular beta-carotene contents. beta-Carotene suppressed UVA induction of MMP-1, MMP-3, and MMP-10-three major MMPs involved in photoaging. HaCaT cells produced weak retinoid activity from beta-carotene, as demonstrated by mild up-regulation of retinoid receptor RAR beta and activation of an RARE-dependent reporter gene. Of the 568 UVA-regulated genes, beta-carotene reduced the UVA effect for 143, enhanced it for 180, and did not interact with UVA for 245 genes. The pathways regulated beta-carotene in interaction with UVA were characterized by genes involved in growth factor signaling, stress response, apoptosis, cell cycle, extracellular matrix (ECM) degradation, tanning, and inflammation.In conclusion, beta-carotene at physiological concentrations interacted with UVA effects by multiple mechanisms that included, but were not restricted to, O-1(2) quenching. With our results, we provide a mechanistic basis for the long-known and clinically established photoprotective effects of beta-carotene in human skin.