Source:http://linkedlifedata.com/resource/pubmed/id/17082253
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
2
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pubmed:dateCreated |
2007-1-17
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pubmed:abstractText |
Although many studies have suggested that estrogen acts as a neuroprotective agent in oxidative stress, the underlying mechanism has not been fully elucidated. In the present study, we examined the effect of 17beta-estradiol (17beta-E2) on H(2)O(2)-induced death signaling in cultured cortical neurons. Exposure of the cortical neurons to H(2)O(2) triggered a series of events, including overactivation of p44/42 MAPK and intracellular Ca(2+) accumulation via voltage-gated Ca(2+) channels and ionotropic glutamate receptors, resulting in apoptotic-like cell death. The MAPK pathway might work as death signaling in our system, because the MAPK pathway inhibitor, U0126, blocked H(2)O(2)-induced MAPK activation, Ca(2+) overload, and cell death. Interestingly, a similar inhibitory effect on H(2)O(2)-triggered MAPK activation, Ca(2+) accumulation, and cell death was observed in cultures incubated with 17beta-E2 for 24 h before exposure to H(2)O(2), suggesting that the protective effect of 17beta-E2 is induced via attenuating overactivation of the MAPK pathway. Furthermore, we found that ionotropic glutamate receptor subunits, including NR2A and GluR2/3, but not NR2B and GluR1, were down-regulated in the 17beta-E2-treated cultures. The down-regulation of these glutamate receptor subunits was also observed after chronic treatment with U0126. Therefore, it is possible that 17beta-E2 down-regulates the expression of the ionotropic glutamate receptors by reducing activity of the MAPK pathway, which might be important for the protective effect of 17beta-E2 against oxidative stress-induced toxicity.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Butadienes,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium Channels,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Estradiol,
http://linkedlifedata.com/resource/pubmed/chemical/Hydrogen Peroxide,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Neuroprotective Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Nitriles,
http://linkedlifedata.com/resource/pubmed/chemical/Oxidants,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Estrogen,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Glutamate,
http://linkedlifedata.com/resource/pubmed/chemical/U 0126
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
0013-7227
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
148
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
627-37
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:17082253-Animals,
pubmed-meshheading:17082253-Butadienes,
pubmed-meshheading:17082253-Calcium,
pubmed-meshheading:17082253-Calcium Channels,
pubmed-meshheading:17082253-Cell Death,
pubmed-meshheading:17082253-Cell Survival,
pubmed-meshheading:17082253-Cells, Cultured,
pubmed-meshheading:17082253-Cerebral Cortex,
pubmed-meshheading:17082253-Down-Regulation,
pubmed-meshheading:17082253-Enzyme Activation,
pubmed-meshheading:17082253-Enzyme Inhibitors,
pubmed-meshheading:17082253-Estradiol,
pubmed-meshheading:17082253-Hydrogen Peroxide,
pubmed-meshheading:17082253-Intracellular Membranes,
pubmed-meshheading:17082253-Mitogen-Activated Protein Kinases,
pubmed-meshheading:17082253-Neurons,
pubmed-meshheading:17082253-Neuroprotective Agents,
pubmed-meshheading:17082253-Nitriles,
pubmed-meshheading:17082253-Oxidants,
pubmed-meshheading:17082253-Oxidative Stress,
pubmed-meshheading:17082253-Rats,
pubmed-meshheading:17082253-Receptors, Estrogen,
pubmed-meshheading:17082253-Receptors, Glutamate
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pubmed:year |
2007
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pubmed:articleTitle |
17beta-estradiol protects cortical neurons against oxidative stress-induced cell death through reduction in the activity of mitogen-activated protein kinase and in the accumulation of intracellular calcium.
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pubmed:affiliation |
Division of Pharmacology/Neurobiology, Biozentrum, University of Basel, Klingelbergstrasse 50/70, CH-4056 Basel, Switzerland.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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