Nrf2-mediated protection against UVA radiation in human skin keratinocytes.

Ultraviolet A (UVA, 320-400 nm) radiation is an oxidizing agent that causes significant damage to cellular components and that leads to photoaging and cancer. It strongly induces NF-E2-related factor 2 (Nrf2) expressions in cultured FEK4 human skin fibroblasts but weakly induces it in transformed HaCaT skin keratinocytes. Nrf2 silencing increases cell damage at a moderate dose of UVA irradiation (250 kJ•m(-2)) in FEK4 fibroblasts, but whether a decrease in Nrf2 sensitizes HaCaT keratinocytes to a moderate to high dose (250-500 kJ•m(-2)) of UVA irradiation (i.e., 400 kJ•m(-2), peak emission 365 nm) is currently unknown. A moderate to high dose of UVA irradiation only slightly increased Nrf2 expression in HaCaT skin keratinocytes. Knockdown of Nrf2 by specific silencing of Nrf2 (siNrf2) strongly increased cell damage as gauged by membrane damage (LDH) and cell viability (MTT assay) following this dose of UVA irradiation. These results suggest that decreased Nrf2 significantly increased UVA irradiation-induced cell damage in skin keratinocytes. Nrf2 may play a role in protecting human skin keratinocytes from UVA radiation-induced damage.