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Role of c-Jun N-terminal kinase-mediated FOXO3a nuclear translocation in neuronal apoptosis in neonatal rats with hypoxic-ischemic brain damage / 中国当代儿科杂志
Chinese Journal of Contemporary Pediatrics ; (12): 458-462, 2017.
Artigo em Chinês | WPRIM | ID: wpr-351324
ABSTRACT
<p><b>OBJECTIVE</b>To explore the mechanisms of neuroprotective effects of c-Jun N-terminal kinase (JNK)/FOXO3a transcription factor signaling pathway inhibition on hypoxic-ischemic neuronal apoptosis in neonatal rats with hypoxic-ischemic brain damage (HIBD).</p><p><b>METHODS</b>Sixty-four 7-day-old Sprague-Dawley rats were divided into four groups hypoxia-ischemia (HI), sham-operated, JNK specific inhibitor AS601245-treated, and DMSO vehicle. Rats' cerebral cortexes were collected at 24 hours after HI. Western blot was used to detect the protein expression of JNK, p-JNK, FOXO3a, nuclear and cytoplasmic FOXO3a, Bim, and CC3. TUNEL staining was used to detect the apoptotic cells.</p><p><b>RESULTS</b>Compared with the sham-operated group, p-JNK protein increased (P<0.01), nuclear protein of FOXO3a increased (P<0.01), cytoplasmic protein decreased (P<0.01), and pro-apoptotic proteins Bim and CC3 increased 24 hours after HI (P<0.01). Compared with the HI and DMSO vehicle groups, p-JNK protein was reduced (P<0.01), nuclear protein of FOXO3a was also reduced (P<0.01), cytoplasmic protein increased (P<0.01), and Bim and CC3 proteins decreased (P<0.01) in the AS601245-treated group 24 hours after HI. TUNEL positive cells were reduced in the AS601245-treated rats compared with the HI and DMSO vehicle groups 24 hours after HI (P<0.01).</p><p><b>CONCLUSIONS</b>JNK activity increases in the neonatal rat brain with HI damage. JNK activity inhibition can inhibit FOXO3a translocation from cytoplasm to nucleus and downregulate the levels of pro-apoptotic proteins Bim and CC3, leading to the reduction of neuronal apoptosis.</p>
Assuntos
Texto completo: DisponíveL Índice: WPRIM (Pacífico Ocidental) Assunto principal: Patologia / Fisiologia / Núcleo Celular / Ratos Sprague-Dawley / Apoptose / Hipóxia-Isquemia Encefálica / Transporte Ativo do Núcleo Celular / Proteínas Quinases JNK Ativadas por Mitógeno / Proteína Forkhead Box O3 / Animais Recém-Nascidos Limite: Animais Idioma: Chinês Revista: Chinese Journal of Contemporary Pediatrics Ano de publicação: 2017 Tipo de documento: Artigo

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Texto completo: DisponíveL Índice: WPRIM (Pacífico Ocidental) Assunto principal: Patologia / Fisiologia / Núcleo Celular / Ratos Sprague-Dawley / Apoptose / Hipóxia-Isquemia Encefálica / Transporte Ativo do Núcleo Celular / Proteínas Quinases JNK Ativadas por Mitógeno / Proteína Forkhead Box O3 / Animais Recém-Nascidos Limite: Animais Idioma: Chinês Revista: Chinese Journal of Contemporary Pediatrics Ano de publicação: 2017 Tipo de documento: Artigo