C1q/tumor necrosis factor-related protein-9 exerts antioxidant and anti-inflammatory effects on oxygen-glucose deprivation/reoxygenation-stimulated neurons by modulating the Akt-GSK-3β-Nrf2 cascade via AdipoR1

Abstract

C1q/tumor necrosis factor-related protein-9 (CTRP9) is linked to diverse pathological conditions via the effects on cell apoptosis, inflammatory response, and oxidative stress. However, its functional relevance in ischemic brain injury is not well determined. The present work aimed to evaluate the role of CTRP9 in ischemia/reperfusion-associated neuronal injury using an in vitro model. The cultured cortical neurons were subjected to oxygen-glucose deprivation/reoxygenation (OGD/R) to simulate ischemia/reperfusion in vitro. CTRP9 level was lowered in cultured neurons exposed to OGD/R. Neurons with overexpressed CTRP9 were resistant to OGD/R-elicited injuries, including neuronal apoptosis, oxidative stress, and pro-inflammatory response. Mechanism research revealed that CTRP9 could boost the activation of the nuclear factor erythroid 2-related factor (Nrf2) pathway associated with modulation of the Akt-glycogen synthase kinase-3β (GSK-3β) axis. CTRP9 regulated the transduction of the Akt-GSK-3β-Nrf2 cascade via adiponectin receptor 1 (AdipoR1). Restraining Nrf2 could diminish CTRP9-mediated neuroprotective effects in OGD/R-injured neurons. Altogether, these results confirmed that CTRP9 exerts a protective effect on OGD/R-injured neurons by modulating Akt-GSK-3β-Nrf2 cascade via AdipoR1. This work suggests a possible link between CTRP9 and ischemic brain injury.