| Summary: | 碩士 === 中國醫藥大學 === 營養學系碩士班 === 99 === UV radiation from sunlight causes a number of acute and chronic detrimental skin effects which can result in inflammation, immunosuppression, premature skin aging(photoaging) and the development of skin malignancies.Much of the skin cell injury caused by exposure of the skin to ultraviolet A (UVA) irradiation,which is associated with the cellular levels of reactive oxygen species (ROS).Overproduction of ROS has been linked to apoptosis and to the damage of proteins, lipids, and nucleic acids. Ellagic acid is demonstrated to possess remarkable antioxidant activity in the organism.In this study,the aim was to investigate the protective role of ellagic acid in human keratinocytes (HaCaT) against UVA-induced oxidative damage and the possible mechanism of the translocation of NF-E2-related factor-2 (Nrf2) into the nucleus. The HaCaT cells were UVA-irradiated and the effects of ellagic acid on cell viability, reactive oxygen species generation, DNA fragmentation and lipid peroxidation were measured. The proteins of Nrf2 and Kelch-like-ECH-associated protein 1 (Keap1) were determined by immunofluorescence staining and Western blot.
In this study, UVA exposure led to a decrease in cell viability and an increase in reactive oxygen species generation in HaCaT cells. Ellagic acid could effectively increase the viability of HaCaT cells after UVA exposure and protect them from UVA-induced oxidative stress. Moreover, ellagic acid increased the level of Nrf2 protein and facilitated Nrf2 accumulation in the nucleus; as a result, the level of antioxidant proteins (HO-1 and SOD) was also upregulated. Importantly, these beneficial effects were attenuated by downregulating Nrf2 expression. The mainfinding was that Keap1 protein, a repressor of Nrf2 in the cytoplasm, was decreased by ellagic acid treatment 24 h.
Our results suggest that ellagic acid can degrade Keap1 protein and elevate intracellular antioxidative protein via the enhanced accumulation in the nucleus of a transcription factor, Nrf2, thereby protecting HaCaT cells from UVA-induced oxidative stress. Ellagic acid could be a more useful natural medicine for the protection of epidermal cells from UVA-induced damage.
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