title: Grape seed proanthocyanidins inhibit UV-radiation-induced oxidative stress and activation of MAPK and NF-kappaB signaling in human epidermal keratinocytes.
abstract: 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.
authors.affiliation: Department of Dermatology, University of Alabama at Birmingham, Volker Hall 557, 1670 University Boulevard, P.O. Box 202, Birmingham, AL 35294, USA.
authors.forename: Sudheer K
authors.initials: SK
authors.lastname: Mantena
authors.forename: Santosh K
authors.initials: SK
authors.lastname: Katiyar
mesh_terms: D000975:Antioxidants / Q000494:pharmacology*; D015153:Blotting, Western; D002460:Cell Line; D004249:DNA Damage / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects; D015227:Lipid Peroxidation / Q000187:drug effects; D020928:Mitogen-Activated Protein Kinases / Q000187:drug effects / Q000378:metabolism; D016328:NF-kappa B / Q000187:drug effects / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects*; D044945:Proanthocyanidins / Q000494:pharmacology*; D012639:Seeds / Q000737:chemistry; D015398:Signal Transduction / Q000187:drug effects*; D013472:Sunlight / Q000009:adverse effects; D014466:Ultraviolet Rays / Q000009:adverse effects*; D027843:Vitis / Q000737:chemistry
chemical_list: D000975:Antioxidants; D016328:NF-kappa B; D044945:Proanthocyanidins; D020928:Mitogen-Activated Protein Kinases