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Photoprotective (UVB) Salen-Manganese Complex (EUK-134)EUK-134 Salen-Manganese Complex is a UVB photoprotective agent, for supplementary use with sunscreens, available in Alyria Corrective Protection SPF 30 Lotion. Salen-manganese complexes exhibit powerful superoxide dismutase and catalase activity, with pharmacologic efficacy in several oxidative-stress-associated disease models. Ultraviolet UVB not only induces direct DNA damage, but also generates oxidative stress. EUK-134, a salen-manganese complex, might therefore confer a direct protection against UVB-induced oxidative stress and consequently alleviate UVB-damage-induced signal transduction. We investigated the effect of EUK-134 on the UVB-induced accumulation and stabilization of the p53 protein. Cells treated with EUK-134 before UVB irradiation showed a significantly lower accumulation of the p53 protein in a concentration-dependent fashion. Furthermore, EUK-134 severely reduced N-terminal phosphorylation of p53. The extracellular signal-regulated kinase ERK and the stress-activated kinases JNK and p38 have been implicated in the UVB-induced N-terminal phosphorylation and accumulation of p53. Pre-treatment with EUK-134 inhibited the UVB-induced activation of these mitogen-activated protein kinase (MAPK) pathways. We hypothesize that EUK-134, by direct protection of the membrane from UVB-induced oxidative damage, reduces oxidative stress induced MAPK signaling and consequently lowers the level of p53 induction. The protection conferred by EUK-134 resulted in a significant increase in cell survival following UVB irradiation. A Synthetic Superoxide Dismutase/Catalase Mimetic (EUK-134) Inhibits Membrane-Damage-Induced Activation of Mitogen-Activated Protein Kinase Pathways and Reduces p53 Accumulation in Ultraviolet B-Exposed Primary Human Keratinocytes David Decraene*, Katrien Smaers*, David Gan , Tom Mammone , Mary Matsui , Daniel Maes , Lieve Declercqà and Marjan Garmyn* Department of Dermatology, University of Leuven, Leuven, Belgium Estée Lauder Companies, Melville, New York, USA àEstée Lauder Coordination Center, Oevel, Belgium Correspondence: Marjan Garmyn, Department of Dermatology, UZ St. Rafaël, Kapucijnenvoer 33, B-3000 Leuven, Belgium. Email: Marjan.Garmyn@med.kuleuven.ac.be Received 14 February 2003; Revised 4 August 2003; Accepted 22 October 2003; Published online 12 February 2004. Keywords: oxidative stress, skin, p53 phosphorylation, manganese compounds, hydrogen peroxide. Abbreviations: AAPH, 2,2'-azobis(2-amidinopropane)dihydrochloride; ERK, extracellular signal-regulated kinase; JNK/SAPK, c-Jun N-terminal kinase/stress-activated protein kinase; MAPK, mitogen-activated protein kinase; ROS, reactive oxygen species; SOD, superoxide dismutase; UV, ultraviolet. Related Skin Care Information, Products and Expert Discussions Flavonolignans from Silybum Marianum Moderate UVA-Induced Oxidative Damage to HaCaT Keratinocytes Cosmetic Dermatology Newsletter Summer 2007 New Roles of Low Density Lipoproteins and Vitamin E in the Pathogenesis of Atherosclerosis Alyria : Alyria Corrective Protection SPF 30 Oil Free Lotion : Photoprotective (UVB) Salen-Manganese Complex (EUK-134) : Alyria Corrective Protection SPF 30 Oil Free Lotion Sunscreen Ingredients : Alyria Corrective Protection SPF 30 Oil Free Lotion Ingredients : |
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