Dipeptidyl-peptidase 3 protects oxygen-glucose deprivation/reoxygenation-injured hippocampal neurons by suppressing apoptosis, oxidative stress and inflammation via modulation of Keap1/Nrf2 signaling.

Xiaoyan Ren, Jiangang Yu, Lili Guo, Hong Ma

International immunopharmacology 2021 Jul

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Dipeptidyl-peptidase 3 (DPP3) plays a key role in regulating apoptosis, oxidative stress and inflammation under various pathological conditions, however, whether DPP3 regulates apoptosis and oxidative stress in neurons undergoing cerebral ischemia/reperfusion injury has not yet been well studied. The goals of this work were to evaluate the role of DPP3 in the regulation of oxygen-glucose deprivation/reoxygenation (OGD/R)-induced apoptosis, oxidative stress and inflammation in HT22 hippocampal neurons. Here, we showed that DPP3 expression was elevated in response to OGD/R in neurons. Knockdown of DPP3 exacerbated OGD/R-induced apoptosis, oxidative stress and inflammation, whilst up-regulation of DPP3 alleviated OGD/R-induced apoptosis, oxidative stress and inflammation in HT22 neurons. Further results revealed that DPP3 enhanced the nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) and promoted transcriptional activity of the anti-oxidant response element (ARE). Additionally, DPP3 was shown to regulate Nrf2/ARE activation in a kelch-like ECH-associated protein 1 (Keap1)-dependent manner. Notably, inhibition of Nrf2 markedly reversed the DPP3-mediated neuroprotective effects against OGD/R injury. Taken together, these findings demonstrate that DPP3 exerts a neuroprotective role in OGD/R-injured neurons by suppressing neuronal apoptosis, oxidative stress and inflammation via modulation of Keap1/Nrf2 signaling. This work suggests DPP3 as a potential target for providing neuroprotective effects during cerebral ischemia/reperfusion injury. Copyright © 2021 Elsevier B.V. All rights reserved.

Citation

Xiaoyan Ren, Jiangang Yu, Lili Guo, Hong Ma. Dipeptidyl-peptidase 3 protects oxygen-glucose deprivation/reoxygenation-injured hippocampal neurons by suppressing apoptosis, oxidative stress and inflammation via modulation of Keap1/Nrf2 signaling. International immunopharmacology. 2021 Jul;96:107595