TRIM21 deficiency confers protection from OGD/R-induced oxidative and inflammatory damage in cultured hippocampal neurons through regulation of the Keap1/Nrf2 pathway

The involvement of tripartite motif-containing protein 21 (TRIM21), a multifunctional protein, in diverse pathological conditions has been reported. However, the role of TRIM21 in cerebral ischemia/reperfusion injury has not been thoroughly investigated. This project is devoted to investigating the possible role of TRIM21 in cerebral ischemia/reperfusion injury using an in vitro model: oxygen-glucose deprivation/reoxygenation (OGD/R)-injured neurons. High TRIM21 levels were found in neurons after OGD/R treatment. The inhibition of TRIM21 ameliorated the deleterious effects of OGD/R on neurons by inhibiting cell apoptosis, oxidative stress and the inflammatory response. Further detections showed that TRIM21 inhibition enhanced the activation of nuclear factor erythroid 2-related factor 2 (Nrf2) pathway induced by OGD/R. However, when the kelch-like ECH-associated protein 1 was knocked-out, the stimulating effects of TRIM21 inhibition on Nrf2 pathway activation was abolished. In addition, the repression of Nrf2 was capable of reversing TRIM21 inhibition-mediated protective effects in OGD/R-injured neurons. Collectively, the observations in this work show that the inhibition of TRIM21 confers protection from OGD/R-induced neuron damage by regulating the Keap1/Nrf2 pathway. Our study outlines the potential relevance of TRIM21 in cerebral ischemia/reperfusion injury and suggests TRIM21 as a viable target for providing neuroprotection.