Knockdown of TRIM32 Protects Hippocampal Neurons from Oxygen–Glucose Deprivation-Induced Injury

Neurons 0303 health sciences NF-E2-Related Factor 2 Ubiquitin-Protein Ligases Apoptosis Hippocampus Neuroprotection Oxygen Tripartite Motif Proteins Oxidative Stress 03 medical and health sciences Glucose Pregnancy Gene Knockdown Techniques Reperfusion Injury Animals Female Rats, Wistar Signal Transduction Transcription Factors
DOI: 10.1007/s11064-019-02857-7 Publication Date: 2019-08-13T12:03:30Z
ABSTRACT
Tripartite motif 32 (TRIM32) is a member of TRIM family that plays a potential role in neural regeneration. However, the biological function of TRIM32 in cerebral ischemia reperfusion injury has not been investigated. In the present study, we evaluated the expression level of TRIM32 in hippocampal neurons following oxygen-glucose deprivation/reperfusion (OGD/R). The results showed that TRIM32 expression was significantly elevated in hippocampal neurons subjected to OGD/R as compared to the neurons cultured in the normoxia condition. To further evaluate the role of TRIM32, hippocampal neurons were transfected with TRIM32 small interfering RNA (si-TRIM32) to knock down TRIM32. We found that knockdown of TRIM32 improved cell viability of OGD/R-stimulated hippocampal neurons. Generation of reactive oxygen species was decreased, while contents of superoxide dismutase and glutathione peroxidase were increased after si-TRIM32 transfection. Knockdown of TRIM32 suppressed cell apoptosis, as proved by the increased bcl-2 expression along with decreased bax expression and caspase-3 activity. We also found that TRIM32 knockdown enhanced OGD/R-induced activation of Nrf2 signaling pathway in hippocampal neurons. Furthermore, siRNA-Nrf2 was transfected to knock down Nrf2. SiRNA-Nrf2 transfection reversed the protective effects of TRIM32 knockdown on neurons. These data suggested that knockdown of TRIM32 protected hippocampal neurons from OGD/R-induced oxidative injury through activating Nrf2 signaling pathway.
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