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dc.contributor.author
Chen, Xiaoyun
dc.contributor.author
Lu, Min
dc.contributor.author
He, Xiju
dc.contributor.author
Ma, Le
dc.contributor.author
Birnbaumer, Lutz
dc.contributor.author
Liao, Yanhong
dc.date.available
2018-06-07T14:44:55Z
dc.date.issued
2016-11
dc.identifier.citation
Chen, Xiaoyun; Lu, Min; He, Xiju; Ma, Le; Birnbaumer, Lutz; et al.; TRPC3/6/7 Knockdown Protects the Brain from Cerebral Ischemia Injury via Astrocyte Apoptosis Inhibition and Effects on NF-кB Translocation; Springer; Molecular Neurobiology; 54; 10; 11-2016; 7555-7566
dc.identifier.issn
0893-7648
dc.identifier.uri
http://hdl.handle.net/11336/47660
dc.description.abstract
Ischemia contributes significantly to morbidity and mortality associated with many common neurological diseases. Calcium overload is an important mechanism of cerebral ischemia and reperfusion (I/R) injury. Despite decades of intense research, an effective beneficial treatment of stroke remains limited; few therapeutic strategies exist to combat the consequences of cerebral ischemia. Traditionally, a “neurocentric” view has dominated research in this field. Evidence is now accumulating that glial cells, especially astrocytes, play an important role in the pathophysiology of cerebral ischemia. Here, we show that transient receptor potential (TRP)C3/6/7 knockout (KO) mice subjected to an I/R procedure demonstrate ameliorated brain injury (infract size), compared to wild-type (WT) control animals. This is accompanied by reduction of NF-кB phosphorylation and an increase in protein kinase B (AKT) phosphorylation in I/R-injured brain tissues in TRPC3/6/7 KO mice. Also, the expression of pro-apoptotic protein Bcl-2 associated X (Bax) is down-regulated and that of anti-apoptotic protein Bcl-2 is upregulated in TRPC3/6/7−/− mice. Astrocytes isolated from TRPC3/6/7 KO mice and subjected to oxygen/glucose deprivation and subsequent reoxygenation (OGD-R, mimicking in vivo I/R injury) also exhibit enhanced Bcl-2 expression, reduced Bax expression, enhanced AKT phosphorylation, and reduced NF-кB phosphorylation. Furthermore, apoptotic rates of TRPC3/6/7 KO astrocytes cultured in OGD-R conditions were reduced significantly compared to WT control. These findings suggest TRPC3/6/7 channels play a detrimental role in brain I/R injury. Deletion of these channels can interfere with the activation of NF-кB (pro-apoptotic), promote activation of AKT (anti-apoptotic), and ultimately, ameliorate brain damage via inhibition of astrocyte apoptosis after cerebral ischemia/reperfusion injury.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Springer
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
Astrocyte
dc.subject
Cerebral Ischemia
dc.subject
Nf-Кb
dc.subject
Trpc3/6/7
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Inmunología
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Medicina Básica
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CIENCIAS MÉDICAS Y DE LA SALUD
dc.title
TRPC3/6/7 Knockdown Protects the Brain from Cerebral Ischemia Injury via Astrocyte Apoptosis Inhibition and Effects on NF-кB Translocation
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2018-06-06T19:40:49Z
dc.identifier.eissn
1559-1182
dc.journal.volume
54
dc.journal.number
10
dc.journal.pagination
7555-7566
dc.journal.pais
Estados Unidos
dc.journal.ciudad
Nueva York
dc.description.fil
Fil: Chen, Xiaoyun. Huazhong University of Science and Technology; China
dc.description.fil
Fil: Lu, Min. Huazhong University of Science and Technology; China
dc.description.fil
Fil: He, Xiju. Huazhong University of Science and Technology; China
dc.description.fil
Fil: Ma, Le. Huazhong University of Science and Technology; China
dc.description.fil
Fil: Birnbaumer, Lutz. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina. National Institute of Environmental Health Sciences; Estados Unidos
dc.description.fil
Fil: Liao, Yanhong. Huazhong University of Science and Technology; China
dc.journal.title
Molecular Neurobiology
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/https://dx.doi.org/10.1007/s12035-016-0227-2
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://link.springer.com/article/10.1007%2Fs12035-016-0227-2
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