TRPC3/6/7 knockdown protects the brain from cerebral ischemia injury via astrocyte apoptosis inhibition and effects on NF-кB translocation

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 r...

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Detalles Bibliográficos
Autores principales: Chen, Xiaoyun, Lu, Min, He, Xiju, Ma, Le, Birnbaumer, Lutz, Liao, Yanhong
Formato: Artículo
Lenguaje:Inglés
Publicado: Springer 2020
Materias:
ENFERMEDADES CEREBROVASCULARES
ISQUEMIA ENCEFALICA
ACCIDENTE CEREBROVASCULAR
TRATAMIENTO MEDICO
PREVENCION Y CONTROL
APOPTOSIS
Acceso en línea:https://repositorio.uca.edu.ar/handle/123456789/9460
Aporte de:
Repositorio Institucional de la Universidad Católica Argentina (UCA) de Universidad Católica Argentina
id I33-R139123456789-9460
record_format dspace
institution Universidad Católica Argentina
institution_str I-33
repository_str R-139
collection Repositorio Institucional de la Universidad Católica Argentina (UCA)
language Inglés
topic ENFERMEDADES CEREBROVASCULARES
ISQUEMIA ENCEFALICA
ACCIDENTE CEREBROVASCULAR
TRATAMIENTO MEDICO
PREVENCION Y CONTROL
APOPTOSIS
spellingShingle ENFERMEDADES CEREBROVASCULARES
ISQUEMIA ENCEFALICA
ACCIDENTE CEREBROVASCULAR
TRATAMIENTO MEDICO
PREVENCION Y CONTROL
APOPTOSIS
Chen, Xiaoyun
Lu, Min
He, Xiju
Ma, Le
Birnbaumer, Lutz
Liao, Yanhong
TRPC3/6/7 knockdown protects the brain from cerebral ischemia injury via astrocyte apoptosis inhibition and effects on NF-кB translocation
topic_facet ENFERMEDADES CEREBROVASCULARES
ISQUEMIA ENCEFALICA
ACCIDENTE CEREBROVASCULAR
TRATAMIENTO MEDICO
PREVENCION Y CONTROL
APOPTOSIS
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.
format Artículo
author Chen, Xiaoyun
Lu, Min
He, Xiju
Ma, Le
Birnbaumer, Lutz
Liao, Yanhong
author_facet Chen, Xiaoyun
Lu, Min
He, Xiju
Ma, Le
Birnbaumer, Lutz
Liao, Yanhong
author_sort Chen, Xiaoyun
title TRPC3/6/7 knockdown protects the brain from cerebral ischemia injury via astrocyte apoptosis inhibition and effects on NF-кB translocation
title_short TRPC3/6/7 knockdown protects the brain from cerebral ischemia injury via astrocyte apoptosis inhibition and effects on NF-кB translocation
title_full TRPC3/6/7 knockdown protects the brain from cerebral ischemia injury via astrocyte apoptosis inhibition and effects on NF-кB translocation
title_fullStr TRPC3/6/7 knockdown protects the brain from cerebral ischemia injury via astrocyte apoptosis inhibition and effects on NF-кB translocation
title_full_unstemmed TRPC3/6/7 knockdown protects the brain from cerebral ischemia injury via astrocyte apoptosis inhibition and effects on NF-кB translocation
title_sort trpc3/6/7 knockdown protects the brain from cerebral ischemia injury via astrocyte apoptosis inhibition and effects on nf-кb translocation
publisher Springer
publishDate 2020
url https://repositorio.uca.edu.ar/handle/123456789/9460
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