QKI 6 ameliorates CIRI through promoting synthesis of triglyceride in neuron and inhibiting neuronal apoptosis associated with SIRT1‐PPARγ‐PGC‐1α axis

• Main Authors: Rui Liu, Hongzeng Li, Jingyuan Deng, Qunqiang Wu, Chunhua Liao, Qun Xiao, Qi Chang
• Format: Article
• Language: English
• Published: Wiley 2021-08-01
• Series: Brain and Behavior
• Subjects: cerebral ischemia/reperfusion injury; middle cerebral artery occlusion; neuronal apoptosis; Quaking 6; sirtuin 1; synthesis of triglyceride
• Online Access: https://doi.org/10.1002/brb3.2271

Abstract Background The stroke induced by ischemia of brain remains high incidence and death rate. The study wanted to confirm the effects of Quaking 6 (QKI 6) on the protection role in neurons of rat model of cerebral ischemia/reperfusion injury (CIRI). Material and methods The rat model with CIRI induced by middle cerebral artery occlusion was well established and rat neurons were isolated to characterize the effects of QKI 6 mediated by sirtuin 1 (SIRT1) on synthesis of triglyceride in neuron and neuronal apoptosis via activation of SIRT1‐peroxisome proliferater‐activated receptor (PPAR)γ‐ peroxisome proliferator‐activated receptor coactivator (PGC)‐1α signaling pathway. Results The expression levels of SIRT1 or QKI 6, and acetylation level of QKI 6 were decreased in neurons of rat model with CIRI. QKI 6 deacetylated and mediated by SIRT1 that contributed to suppressing the progression of neuronal apoptosis in rat through promoting synthesis of triglyceride in vivo and in vitro via SIRT1‐PPARγ‐PGC‐1α signaling pathway, then inhibiting CIRI. Conclusions Our results demonstrated SIRT1 deacetylates QKI 6, the RNA‐binding protein, that affects significantly the synthesis of triglyceride in neurons of CIRI rat model. Moreover, it activated transcription factor peroxisome proliferator‐activated receptorγ coactivator‐1α (PGC‐1α) through post‐transcriptional regulation of the expression of PPARγ, and further enhanced synthesis of triglyceride, thereby restrained the progression of neural apoptosis and CIRI.