Ischemic preconditioning protects the brain against injury via inhibiting CaMKII-nNOS signaling pathway.
Brain Res
; 1634: 140-149, 2016 Mar 01.
Article
en En
| MEDLINE
| ID: mdl-26794251
ABSTRACT
Although studies have shown that cerebral ischemic preconditioning (IPC) can ameliorate ischemia/reperfusion (I/R) induced brain damage, but its precise mechanisms remain unknown. Therefore, the aim of this study was to investigate the neuroprotective mechanisms of IPC against ischemic brain damage induced by cerebral I/R and to explore whether the Calcium/calmodulin-dependent protein kinase II (CaMKII)-mediated up-regulation of nNOS ser847-phosphorylation signaling pathway contributed to the protection provided by IPC. Transient global brain ischemia was induced by 4-vessel occlusion in adult male Sprague-Dawley rats. The rats were pretreated with 3 min of IPC alone or KN62 (selective antagonist of CaMKII) treatment before IPC, after reperfusion for 3 days, 6 min ischemia was induced. Cresyl violet staining was used to examine the survival of hippocampal CA1 pyramidal neurons. Immunoblotting was performed to measure the phosphorylation of CaMKII, nNOS, c-Jun and the expression of FasL. Immunoprecipitation was used to examine the binding between PSD95 and nNOS. The results showed that IPC could significantly protect neurons against cerebral I/R injury, furthermore, the combination of PSD95 and nNOS was increased, coinstantaneously the phosphorylation of CaMKII and nNOS (ser847) were up-regulated, however the activation of c-Jun and FasL were reduced. Conversely, KN62 treatment before IPC reversed all these effects of IPC. Taken together, the results suggest that IPC could diminish ischemic brain injury through CaMKII-mediated up-regulation of nNOS ser847-phosphorylation signaling pathway.
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Banco de datos:
MEDLINE
Asunto principal:
Isquemia Encefálica
/
Precondicionamiento Isquémico
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Óxido Nítrico Sintasa de Tipo I
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Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina
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Región CA1 Hipocampal
Límite:
Animals
Idioma:
En
Revista:
Brain Res
Año:
2016
Tipo del documento:
Article