Cyclic helix B peptide alleviates proinflammatory cell death and improves functional recovery after traumatic spinal cord injury

作者：Yu Xu, Yibo Geng, Hui Wang, Haojie Zhang, Jianjun Qi, Feida Li, Xinli Hu, Yituo Chen, Haipeng Si, Yao Li, Xiangyang Wang, Huazi Xu, Jianzhong Kong, Yuepiao Cai, Aimin Wu, Wenfei Ni, Jian Xiao, Kailiang Zhou · 发表于：Redox Biology · 年份：2023 · DOI：10.1016/j.redox.2023.102767 · 被引用次数：44 · 研究领域：Inflammasome and immune disorders、Autophagy in Disease and Therapy、Erythropoietin and Anemia Treatment

BACKGROUND: Necroptosis and pyroptosis, two types of proinflammatory programmed cell death, were recently found to play important roles in spinal cord injury (SCI). Moreover, cyclic helix B peptide (CHBP) was designed to maintain erythropoietin (EPO) activity and protect tissue against the adverse effects of EPO. However, the protective mechanism of CHBP following SCI is still unknown. This research explored the necroptosis- and pyroptosis-related mechanism underlying the neuroprotective effect of CHBP after SCI. METHODS: Gene Expression Omnibus (GEO) datasets and RNA sequencing were used to identify the molecular mechanisms of CHBP for SCI. A mouse model of contusion SCI was constructed, and HE staining, Nissl staining, Masson staining, footprint analysis and the Basso Mouse Scale (BMS) were applied for histological and behavioural analyses. qPCR, Western blot analysis, immunoprecipitation and immunofluorescence were utilized to analyse the levels of necroptosis, pyroptosis, autophagy and molecules associated with the AMPK signalling pathway. RESULTS: The results revealed that CHBP significantly improved functional restoration, elevated autophagy, suppressed pyroptosis, and mitigated necroptosis after SCI. 3-Methyladenine (3-MA), an autophagy inhibitor, attenuated these beneficial effects of CHBP. Furthermore, CHBP-triggered elevation of autophagy was mediated by the dephosphorylation and nuclear translocation of TFEB, and this effect was due to stimulation of the AMPK-FOXO3...