TPPU, a sEH Inhibitor, Attenuates Corticosterone-Induced PC12 Cell Injury by Modulation of BDNF-TrkB Pathway.
J Mol Neurosci
; 67(3): 364-372, 2019 Mar.
Article
em En
| MEDLINE
| ID: mdl-30644034
ABSTRACT
High level of corticosterone (CORT) is toxic to neurons and plays an important role in depression-like behavior and chronic stress. Our previous study showed that TPPU, a soluble epoxide hydrolase (sEH) inhibitor (sEHI), induces an antidepressant effect in animal models. However, the underlying mechanism is not clear. In this study, we investigated the protective effect of TPPU on PC12 cells against CORT-induced cytotoxicity and its underlying mechanism. We found that TPPU and the sEH substrate epoxyeicosatrienoic acids (EETs) protected PC12 cells from the CORT-induced injury by increasing cell viability and inhibiting apoptosis. Furthermore, TPPU and EETs also blocked the CORT-mediated downregulation of BDNF. Blocking the BDNF-TrkB pathway by the TrkB inhibitor K252a abolished the protective effect of TPPU. Taken together, our results suggest that sEHI could protect PC12 cells against the CORT-induced cytotoxicity via the BDNF-TrkB signaling pathway.
Palavras-chave
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Compostos de Fenilureia
/
Piperidinas
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Fármacos Neuroprotetores
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Fator Neurotrófico Derivado do Encéfalo
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Receptor trkB
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Inibidores Enzimáticos
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Epóxido Hidrolases
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
J Mol Neurosci
Assunto da revista:
BIOLOGIA MOLECULAR
/
NEUROLOGIA
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
China