TPPU, a sEH Inhibitor, Attenuates Corticosterone-Induced PC12 Cell Injury by Modulation of BDNF-TrkB Pathway
| Autor: | Qiong Wu, Quanzhong Chang, Danxin Meng, Jingfang Song |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Epoxide hydrolase 2 endocrine system Apoptosis Tropomyosin receptor kinase B Pharmacology PC12 Cells 03 medical and health sciences Cellular and Molecular Neuroscience chemistry.chemical_compound 0302 clinical medicine Downregulation and upregulation Piperidines Animals Receptor trkB Viability assay Enzyme Inhibitors Cytotoxicity Epoxide Hydrolases Chemistry Brain-Derived Neurotrophic Factor Phenylurea Compounds General Medicine Rats 030104 developmental biology Neuroprotective Agents nervous system K252a Signal transduction Corticosterone hormones hormone substitutes and hormone antagonists 030217 neurology & neurosurgery Signal Transduction |
| Zdroj: | Journal of molecular neuroscience : MN. 67(3) |
| ISSN: | 1559-1166 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink