TPPU, a sEH Inhibitor, Attenuates Corticosterone-Induced PC12 Cell Injury by Modulation of BDNF-TrkB Pathway
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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.
KeywordsSoluble epoxide hydrolase inhibitor (sEHI) Brain-derived neurotrophic factor Corticosterone Neuroprotective
Brain-derived neurotrophic factor
- PEG 400
Polyethylene glycol 400
Soluble epoxide hydrolase
Soluble epoxide hydrolase inhibitor
1-Trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea or N-[1-(1-oxopropyl)-4-piperidinyl]-N′-[4-(trifluoromethoxy)phenyl]-urea
We would like to thank all the members of our research team for their scientific support and helpful advice.
Quanzhong Chang and Qiong Wu contributed to the conception and design of the study, acquisition, analysis and interpretation of data, and manuscript drafting. Danxin Meng and Jingfang Song contributed to Hoechst analysis, Western blotting, CCK-8 analysis, and cell culture. All authors critically revised the manuscript and approved the final manuscript.
This work is partly supported by the Doctor Foundation of Luohe Medical College (grant numbers 2014-DF-004, to Dr Wu), and Plan subjects on science and technology of Henan province (grant number 172102310605 to Dr Wu).
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