Mantena SK, Katiyar SKGrape seed proanthocyanidins inhibit UV-radiation-induced oxidative stress and activation of MAPK and NF-kappaB signaling in human epidermal keratinocytes. Free Radic Biol Med 40:1603-1614

Department of Dermatology, University of Alabama at Birmingham, Volker Hall 557, 1670 University Boulevard, P.O. Box 202, Birmingham, AL 35294, USA.
Free Radical Biology and Medicine (Impact Factor: 5.74). 06/2006; 40(9):1603-14. DOI: 10.1016/j.freeradbiomed.2005.12.032
Source: PubMed


Solar ultraviolet (UV) radiation-induced oxidative stress has been implicated in various skin diseases. Here, we report the photoprotective effect of grape seed proanthocyanidins (GSPs) on UV-induced oxidative stress and activation of mitogen-activated protein kinase (MAPK) and NF-kappaB signaling pathways using normal human epidermal keratinocytes (NHEK). Treatment of NHEK with GSPs inhibited UVB-induced hydrogen peroxide (H2O2), lipid peroxidation, protein oxidation, and DNA damage in NHEK and scavenged hydroxyl radicals and superoxide anions in a cell-free system. GSPs also inhibited UVB-induced depletion of antioxidant defense components, such as glutathione peroxidase, catalase, superoxide dismutase, and glutathione. As UV-induced oxidative stress mediates activation of MAPK and NF-kappaB signaling pathways, we determined the effects of GSPs on these pathways. Treatment of NHEK with GSPs inhibited UVB-induced phosphorylation of ERK1/2, JNK, and p38 proteins of the MAPK family at the various time points studied. As UV-induced H2O2 plays a major role in activation of MAPK proteins, NHEK were treated with H2O2 with or without GSPs and other known antioxidants, viz. (-)-epigallocatechin-3-gallate, silymarin, ascorbic acid, and N-acetylcysteine. It was observed that H2O2-induced phosphorylation of ERK1/2, JNK, and p38 was decreased by these antioxidants. Under identical conditions, GSPs also inhibited UVB-induced activation of NF-kappaB/p65, which was mediated through inhibition of degradation and activation of IkappaBalpha and IKKalpha, respectively. Together, these results suggest that GSPs could be useful in the attenuation of UV-radiation-induced oxidative stress-mediated skin diseases in human skin.

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Available from: Sudheer Mantena, Dec 05, 2014
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    • "6C–D). Previous study showed that exposure of UVB radiation resulted in the degradation of IκBα protein and subsequent activation and translocation of NF-κB/p65 to the nucleus (Mantena and Katiyar, 2006). To study the inhibitory effect of C3G on UVB-induced degradation of IκBα, we determined the cytoplasmic level of IκBα protein expression. "
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    ABSTRACT: Skin cancer is one of the most commonly diagnosed cancers in the United States. Exposure to ultraviolet-B (UVB) radiation induces inflammation and photocarcinogenesis in mammalian skin. Cyanidin-3-glucoside (C3G), a member of the anthocyanin family, is present in various vegetables and fruits especially in edible berries, and displays potent antioxidant and anticarcinogenic properties. In this study, we have assessed the in vivo effects of C3G on UVB irradiation induced chronic inflammatory responses in SKH-1 hairless mice, a well-established model for UVB-induced skin carcinogenesis. Here, we show that C3G inhibited UVB-induced skin damage and inflammation in SKH-1 hairless mice. Our results indicate that C3G inhibited glutathione depletion, lipid peroxidation and myeloperoxidation in mouse skin by chronic UVB exposure. C3G significantly decreased the production of UVB-induced pro-inflammatory cytokines, such as IL-6 and TNF-α, associated with cutaneous inflammation. Likewise, UVB-induced inflammatory responses were diminished by C3G as observed by a remarkable reduction in the levels of phosphorylated MAP kinases, Erk1/2, p38, JNK1/2 and MKK4. Furthermore, C3G also decreased UVB-induced cyclooxygenase-2 (COX-2), PGE2 and iNOS levels, which are well-known key mediators of inflammation and cancer. Treatment with C3G inhibited UVB-induced nuclear translocation of NF-κB and degradation of IκBα in mice skin. Immunofluorescence assay revealed that topical application of C3G inhibited the expression of 8-hydroxy-2'-deoxyguanosine, proliferating cell nuclear antigen, and cyclin D1 in chronic UVB exposed mouse skin. Collectively, these data indicates that C3G can provide substantial protection against the adverse effects of UVB radiation by modulating UVB-induced MAP kinase and NF-κB signaling pathways.
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    • "Mantena and Katiyar [54] attempted to define the photoprotective mechanism of action of GSPs. Researchers observed that in vitro treatment of NHEK with GSPs resulted in the prevention of UVB-induced depletion of antioxidant defense enzymes (GPx, catalase, SOD, and GSH) and H2O2 production. "
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    • "Moon et al. (2008) showed that ERK kinase was early activated after UVB irradiation and then decreased to a baseline level at 24 h. Also, Mantena and Katiyar (2005) reported that the maximum phosphorylation of ERK 1/2 Fig. 5. Effect of BM extract on UVB-induced Bcl-2 and Bax positive cells in SKH-1 hairless mouse skin exposed to one and multiple doses of UVB. (a and b) Photomicrograph of skin section labeled with Bcl-2 and Bax antibodies. "
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