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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
5
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pubmed:dateCreated |
2001-6-6
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pubmed:abstractText |
Estrogen replacement therapy in menopausal women has been suggested to be beneficial in preventing the progression of cognitive impairment in Alzheimer disease. We demonstrated previously that the phosphatidylinositol 3-kinase (PI3-K)/Akt signal transduction pathway plays a pivotal role on the neuroprotection provided by 17beta-estradiol against acute glutamate toxicity. In the present study, we investigated the mechanism of neuroprotection against apoptosis because acute glutamate toxicity predominantly induced necrosis. 17beta-estradiol provided neuroprotection against apoptosis induced by staurosporine. This neuroprotection was inhibited by pretreatment with a PI3-K inhibitor, LY294002. An estrogen receptor specific antagonist, ICI182780, also suppressed the neuroprotection provided by 17beta-estradiol. Western blotting analysis demonstrated that treatment with 17beta-estradiol induced the phosphorylation of Akt within 5 min, which was suppressed by pretreatment with LY294002 and ICI182780. Furthermore, 17beta-estradiol induced phosphorylation of the cAMP response element binding protein (CREB) at Ser(133) within 15 min and then upregulated Bcl-2 in a PI3-K/Akt-dependent manner. Because CREB is known to be a transcription factor for Bcl-2, these results suggest that 17beta-estradiol exerts its antiapoptotic effects by CREB phosphorylation and Bcl-2 upregulation via nongenomic activation of the PI3-K/Akt pathway in cultured cortical neurons.
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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/Akt1 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP Response...,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Estradiol,
http://linkedlifedata.com/resource/pubmed/chemical/Glutamic Acid,
http://linkedlifedata.com/resource/pubmed/chemical/Neuroprotective Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositol 3-Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-akt,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-bcl-2,
http://linkedlifedata.com/resource/pubmed/chemical/Serine,
http://linkedlifedata.com/resource/pubmed/chemical/Staurosporine
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
0360-4012
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pubmed:author |
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pubmed:copyrightInfo |
Copyright 2001 Wiley-Liss, Inc.
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pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
64
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
466-75
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:11391701-Alzheimer Disease,
pubmed-meshheading:11391701-Animals,
pubmed-meshheading:11391701-Apoptosis,
pubmed-meshheading:11391701-Cells, Cultured,
pubmed-meshheading:11391701-Cerebral Cortex,
pubmed-meshheading:11391701-Cyclic AMP Response Element-Binding Protein,
pubmed-meshheading:11391701-Enzyme Inhibitors,
pubmed-meshheading:11391701-Estradiol,
pubmed-meshheading:11391701-Estrogen Replacement Therapy,
pubmed-meshheading:11391701-Fetus,
pubmed-meshheading:11391701-Glutamic Acid,
pubmed-meshheading:11391701-Menopause,
pubmed-meshheading:11391701-Nerve Degeneration,
pubmed-meshheading:11391701-Neurons,
pubmed-meshheading:11391701-Neuroprotective Agents,
pubmed-meshheading:11391701-Phosphatidylinositol 3-Kinases,
pubmed-meshheading:11391701-Phosphorylation,
pubmed-meshheading:11391701-Protein-Serine-Threonine Kinases,
pubmed-meshheading:11391701-Proto-Oncogene Proteins,
pubmed-meshheading:11391701-Proto-Oncogene Proteins c-akt,
pubmed-meshheading:11391701-Proto-Oncogene Proteins c-bcl-2,
pubmed-meshheading:11391701-Rats,
pubmed-meshheading:11391701-Rats, Sprague-Dawley,
pubmed-meshheading:11391701-Serine,
pubmed-meshheading:11391701-Signal Transduction,
pubmed-meshheading:11391701-Staurosporine
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pubmed:year |
2001
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pubmed:articleTitle |
Nongenomic antiapoptotic signal transduction by estrogen in cultured cortical neurons.
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pubmed:affiliation |
Department of Neurology, Kyoto University Graduate School of Medicine, 54 Shogoin-Kawaharacho, Sakyo-ku, Kyoto 606-8507, Japan.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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