CTRP3 protects hippocampal neurons from oxygen-glucose deprivation-induced injury through the AMPK/Nrf2/ARE pathway

C1q/TNF-related protein 3 (CTRP3), a member of CTRP family, has been found to have neuroprotective effect. In the current study, we investigated the protective role of CTRP3 in hippocampal neurons exposed to oxygen-glucose deprivation/reperfusion (OGD/R).

The mRNA and protein levels of CTRP3 in OGD/R-stimulated hippocampal neurons were measured using qRT-PCR and western blot analysis, respectively. CCK-8 assay was performed to assess cell viability. ROS production was measured using the fluorescence probe 2',7'-dichlorofluorescein diacetate (H₂DCFDA). The activities of SOD and GPx were determined using ELISA. Cell apoptosis was assessed. Luciferase reporter assay was carried out to assess the activation of ARE). The levels of p-AMPK and Nrf2 were measured using western blot.

Our results showed that the expression of CTRP3 was significantly downregulated in hippocampal neuronal cells exposed to OGD/R. Overexpression of CTRP3 improved cell viability of OGD/R-induced hippocampal neurons. In addition, overexpression of CTRP3 attenuated the OGD/R-caused oxidative stress with decreased ROS production and increased activities of SOD and GPx. Moreover, CTRP3 caused a significant increase in bcl-2 expression and decreases in bax expression and caspase-3 activity. Furthermore, CTRP3 overexpression significantly upregulated the levels of p-AMPK and Nrf2, as well induced the activation of ARE in OGD-R-induced hippocampal neurons. CTRP3 upregulated the mRNA expression levels of HO-1, NQO-1 and GPx-3. Additionally, treatment with the inhibitor of AMPK partially reversed the neuroprotective effect of CTRP3 in OGD/R-exposed neurons.

CTRP3 exerted protective effect on OGD/R-induced cerebral injury, which was regulated by AMPK/Nrf2/ARE pathway.