[show abstract][hide abstract] ABSTRACT: Niacin and its related derivatives have been shown to have effects on cellular activities. However, the molecular mechanism of its reduced immunosuppressive effects and photoprotective effects remains unclear. In this study, we investigated the molecular mechanism of the photoprotective effect of niacin in ultraviolet (UV)-irradiated human skin keratinocytes (HaCaT cells). We found that niacin effectively suppressed the UV-induced cell death and cell apoptosis of HaCaT cells. Existing data have shown that AKT activation is involved in the cell survival process. Yet, the potential mechanism of niacin in protection against UV-induced skin damage has thus far not fully been eluvidated. We observed that niacin pretreatment enhances UV induced activation of AKT (Ser473 phosphorylation) as well as that of the downstream signal mTOR (S6 and 4E-BP1 phosphorylation). The PI3K/AKT inhibitor, LY294002, and the mTOR inhibitor, rapamycin, largely neutralized the protective effects of niacin, suggesting that AKT and downstream signaling mTOR/S6 activation are necessary for the niacin-induced protective effects against UV-induced cell death and cell apoptosis. Collectively, our data suggest that niacin may be utilized to prevent UV-induced skin damage and provide a novel mechanism of its photoprotective effects against the UV radiation of sunlight by modulating both AKT and downstream mTOR signaling pathways.
International Journal of Molecular Medicine 04/2012; 29(4):593-600. · 1.96 Impact Factor
[show abstract][hide abstract] ABSTRACT: Our previous study has shown that VIT1 gene in Chinese vitiligo patients is de facto the FBXO11 gene, and the silencing of that gene has an impact on the ultrastructure of melanocytes. In this study, we further identified the role of the FBXO11 gene in melanocytes and the relationship between dilated endoplasmic reticulum (ER) and tyrosinase by inhibition and overexpression of FBXO11 gene. Cell proliferation, apoptosis, cycle and migration of melanocytes were examined when the FBXO11 gene was silenced or overexpressed. The results showed that FBXO11 gene promoted cell proliferation and suppressed cell apoptosis, and yet had little effect on cell migration. Obvious swelling of ER was found in the cells transfected with siRNA of FBXO11 gene. Interestingly, protein level of tyrosinase was extraordinarily high following inhibition of FBXO11 gene. Further examination revealed that tyrosinase and calreticulin were co-localized in ER of transfected cells following siRNA of FBXO11 gene, suggesting that tyrosinase could not be exported from ER effectively. Collectively, our results support the notion that FBXO11 plays an important role in regulating proliferation and apoptosis of melanocytes, and functional export of tyrosinase from ER in vitiligo melanocytes.
International Journal of Molecular Medicine 07/2010; 26(1):57-65. · 1.96 Impact Factor