Linked Life Data

16084662

Source:http://linkedlifedata.com/resource/pubmed/id/16084662

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2005-9-5
pubmed:abstractText
Our group and others have demonstrated that 17beta-estradiol (E2) induces neurotrophic and neuroprotective responses in hippocampal and cortical neurons which are dependent upon the Src/extracellular signal-regulated kinase (ERK) signaling pathways. The purpose of this study was to determine the upstream mechanism(s) that initiates the signaling cascade leading to E2-inducible neuroprotection. We tested the hypothesis that E2 activates rapid Ca(2+) influx in hippocampal neurons, which would lead to activation of the Src/ERK signaling cascade and up-regulation of Bcl-2 protein expression. Using fura-2 ratiometric Ca(2+) imaging, we demonstrated that E2 induced a rapid rise of intracellular Ca(2+) concentration ([Ca(2+)](i)) within minutes of exposure which was blocked by an L-type Ca(2+) channel antagonist. Inhibition of L-type Ca(2+) channels resulted in a loss of E2 activation of the Src/ERK cascade, activation of cyclic-AMP response element binding protein (CREB) and subsequent increase in Bcl-2. Real-time intracellular Ca(2+) imaging combined with pERK immunofluorescence, demonstrated that E2 induced [Ca(2+)](i) was coincident with ERK activation in the same neuron. Small interfering RNA knockdown of CREB resulted in a loss of E2 activation of CREB and subsequent E2-induced increase of Bcl-2 expression. We further demonstrated the presence of specific membrane E2 binding sites in hippocampal neurons. Together, these data indicate that E2-induced Ca(2+) influx via the L-type Ca(2+) channel is required for E2 activation of the Src/ERK/CREB/Bcl-2 signaling. Implications of these data for understanding estrogen action in brain and use of estrogen therapy for prevention of neurodegenerative disease are discussed.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0306-4522
pubmed:author
pubmed:issnType
Print
pubmed:volume
135
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
59-72
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:16084662-Animals, pubmed-meshheading:16084662-Binding, Competitive, pubmed-meshheading:16084662-Calcium, pubmed-meshheading:16084662-Calcium Channels, L-Type, pubmed-meshheading:16084662-Cyclic AMP Response Element-Binding Protein, pubmed-meshheading:16084662-Estradiol, pubmed-meshheading:16084662-Female, pubmed-meshheading:16084662-Genes, bcl-2, pubmed-meshheading:16084662-Hippocampus, pubmed-meshheading:16084662-Immunohistochemistry, pubmed-meshheading:16084662-Mitogen-Activated Protein Kinases, pubmed-meshheading:16084662-Neurons, pubmed-meshheading:16084662-Neuroprotective Agents, pubmed-meshheading:16084662-Pregnancy, pubmed-meshheading:16084662-RNA, Small Interfering, pubmed-meshheading:16084662-Rats, pubmed-meshheading:16084662-Rats, Sprague-Dawley, pubmed-meshheading:16084662-Receptors, Estrogen, pubmed-meshheading:16084662-Signal Transduction, pubmed-meshheading:16084662-src-Family Kinases
pubmed:year
2005
pubmed:articleTitle
17Beta-estradiol induced Ca2+ influx via L-type calcium channels activates the Src/ERK/cyclic-AMP response element binding protein signal pathway and BCL-2 expression in rat hippocampal neurons: a potential initiation mechanism for estrogen-induced neuroprotection.
pubmed:affiliation
Neuroscience Program, University of Southern California, 1985 Zonal Avenue, Los Angeles, CA 90089-9121, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural