Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2007-1-17
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
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
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0013-7227
pubmed:author
pubmed:issnType
Print
pubmed:volume
148
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
627-37
pubmed:dateRevised
2009-11-19
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
pubmed:year
2007
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.
pubmed:affiliation
Division of Pharmacology/Neurobiology, Biozentrum, University of Basel, Klingelbergstrasse 50/70, CH-4056 Basel, Switzerland.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't