Photoprotective (UVB) Salen-Manganese Complex (EUK-134): Melbourne Dermatology Skin Care

Clinical Procedures and Topics

abbreviations accumulation activated activation against agent alleviate alyria amidinopropane associated before belgium catalase cell cells center companies complex complexes compounds concentration confer conferred consequently correspondence damage danielÊmaes davidÊdecraene davidÊgan department dependent dermatology dihydrochloride direct disease dismutase effect efficacy email exhibit exposed extracellular fashion following furthermore garmyn generates human hydrogen hypothesize induced inhibits investigated irradiation kapucijnenvoer katrienÊsmaers keratinocytes keywords kinase kinases kuleuven lauder leuven level lieveÊdeclercqà lotion lower lowers manganese mapk marjan marjanÊgarmyn maryÊmatsui melville membrane mimetic mitogen models noshade oevel online oxidative oxygen pathways peroxide pharmacologic phosphorylation photoprotective protection protein reduces regulated salen signal size stress superoxide terminal ultraviolet ÊfebruaryÊ

Photoprotective (UVB) Salen-Manganese Complex (EUK-134)

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.

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Photoprotective (UVB) Salen-Manganese Complex (EUK-134)


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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. 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