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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
2
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pubmed:dateCreated |
2011-2-7
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pubmed:abstractText |
Lipid peroxidation (LPO) end-product 4-hydroxynonenal (4-HNE) has been implicated in the mechanism of retinopathy. Lately it has been shown that besides being cytotoxic, 4-HNE plays an important role in oxidative stress-induced signaling. In this study, we have investigated the effect of 4-HNE on epidermal growth factor receptor (EGFR)-mediated signaling, its potential functional consequences, and the regulatory role of the 4-HNE metabolizing isozymes, glutathione S-transferase A4-4 (GSTA4-4) on this signaling in retinal pigment epithelial (RPE) cells. Our results showed that consistent with its known toxicity at relatively higher concentrations, 4-HNE induced cell death in RPE. However, at lower concentrations (as low as 0.1 ?M) 4-HNE triggered phosphorylation of EGFR and activation of its down stream signaling components ERK1/2 and Akt that are known to be involved in cell proliferation. These effects of 4-HNE on EGFR could be attenuated by the over expression of GSTA4-4 that reduces intracellular levels of 4-HNE. Our results also indicated that 4-HNE-induced activation of EGFR is a protective mechanism against oxidative stress because EGFR, MEK, and PI3K inhibitors potentiated the toxicity of 4-HNE and also inhibited wound healing in a RPE cell model. These studies suggest that as an initial response to oxidative stress, 4-HNE induces protective mechanism(s) in RPE cells through EGFR-mediated signaling.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/4-hydroxy-2-nonenal,
http://linkedlifedata.com/resource/pubmed/chemical/Aldehydes,
http://linkedlifedata.com/resource/pubmed/chemical/Caspase 3,
http://linkedlifedata.com/resource/pubmed/chemical/Cysteine Proteinase Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/EGFR protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Extracellular Signal-Regulated MAP...,
http://linkedlifedata.com/resource/pubmed/chemical/Glutathione Transferase,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-akt,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Epidermal Growth Factor,
http://linkedlifedata.com/resource/pubmed/chemical/leukotriene-C4 synthase
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
1096-0007
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pubmed:author |
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pubmed:copyrightInfo |
Copyright © 2010 Elsevier Ltd. All rights reserved.
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pubmed:issnType |
Electronic
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pubmed:volume |
92
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
147-54
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pubmed:dateRevised |
2011-9-26
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pubmed:meshHeading |
pubmed-meshheading:21134369-Aldehydes,
pubmed-meshheading:21134369-Apoptosis,
pubmed-meshheading:21134369-Blotting, Western,
pubmed-meshheading:21134369-Caspase 3,
pubmed-meshheading:21134369-Cell Line, Transformed,
pubmed-meshheading:21134369-Cell Survival,
pubmed-meshheading:21134369-Cells, Cultured,
pubmed-meshheading:21134369-Cysteine Proteinase Inhibitors,
pubmed-meshheading:21134369-Enzyme Inhibitors,
pubmed-meshheading:21134369-Extracellular Signal-Regulated MAP Kinases,
pubmed-meshheading:21134369-Fluorescent Antibody Technique, Indirect,
pubmed-meshheading:21134369-Glutathione Transferase,
pubmed-meshheading:21134369-Humans,
pubmed-meshheading:21134369-Male,
pubmed-meshheading:21134369-Oxidative Stress,
pubmed-meshheading:21134369-Phosphorylation,
pubmed-meshheading:21134369-Proto-Oncogene Proteins c-akt,
pubmed-meshheading:21134369-Receptor, Epidermal Growth Factor,
pubmed-meshheading:21134369-Retinal Pigment Epithelium,
pubmed-meshheading:21134369-Signal Transduction,
pubmed-meshheading:21134369-Transfection,
pubmed-meshheading:21134369-Wound Healing
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pubmed:year |
2011
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pubmed:articleTitle |
Role of 4-hydroxynonenal in epidermal growth factor receptor-mediated signaling in retinal pigment epithelial cells.
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pubmed:affiliation |
Department of Molecular Biology and Immunology, University of North Texas Health Science Center, 3500 Camp Bowie Boulevard, Fort Worth, TX 76107, USA.
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pubmed:publicationType |
Journal Article,
Research Support, N.I.H., Extramural
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