DADLE promotes motor function recovery by inhibiting cytosolic phospholipase A2 mediated lysosomal membrane permeabilization after spinal cord injury

doi:10.1111/bph.16255

科研成果详情

题名	DADLE promotes motor function recovery by inhibiting cytosolic phospholipase A2 mediated lysosomal membrane permeabilization after spinal cord injury
作者	Chen, Yituo1,2,3; Zhang, Haojie 1,2,3; Jiang, Liting1,2,3; Cai, Wanta1,2,3; Kuang, Jiaxuan4; Geng, Yibo1,2,3; Xu, Hui1,2,3; Li, Yao1,2,3; Yang, Liangliang5; Cai, Yuepiao5; Wang, Xiangyang1,2,3; Xiao, Jian5; Ni, Wenfei1,2,3; Zhou, Kailiang 1,2,3
发表日期	2023-10-21
发表期刊	British journal of pharmacology 影响因子和分区
语种	英语
原始文献类型	Journal Article
关键词	Autophagic flux Cytosolic phospholipase A2 DADLE Lysosomal membrane permeabilization Necroptosis
其他关键词	DELTA-OPIOID RECEPTOR ; CONCISE GUIDE ; AUGMENTING AUTOPHAGY ; REGULATE AUTOPHAGY ; CELL-DEATH ; BRAIN ; PYROPTOSIS ; TARGET ; AMPK
摘要	Autophagy is a protective factor for controlling neuronal damage, while necroptosis promotes neuroinflammation after spinal cord injury (SCI). DADLE (d-Ala2, d-Leu5) is a selective agonist for delta opioid receptor (DOR) and has been identified as a promising drug for its neuroprotective effects. Our present work aims to investigate the therapeutic effect of DADLE on locomotive function recovery following SCI and its concrete mechanism., Spinal cord contusion model was constructed and DADLE was delivered though intraperitoneal administration (16mg/kg) in mice for following experiments. Motor function was assessed by footprint and BMS score analysis. Western blotting evaluated related protein expression. Immunofluorescence exhibited protein expression in each cell and its distribution. Network pharmacology analysis was used to find related signalling pathways., DADLE promoted functional recovery after SCI. In SCI model of mice, DADLE significantly promoted autophagic flux and inhibited necroptosis. Concurrently, DADLE restored autophagic flux by decreasing lysosomal membrane permeabilization (LMP). And chloroquine administration reversed the protective effect of DADLE to inhibit necroptosis. Further analysis identified that DADLE decreased phosphorylated cPLA2 and overexpression of cPLA2 partially reversed DADLE inhibition effect of LMP and necroptosis, as well as the promotion effect of autophagy. Finally, AMPK/SIRT1/p38 signalling pathway regulated cPLA2 after DADLE treatment following SCI, and administration of naltrindole to block interaction between DADLE and DOR abolished DADLE effect on AMPK signalling pathway., DADLE exerts neuroprotective effects on SCI by promoting autophagic flux and inhibiting necroptosis by decreasing LMP via activating DOR/AMPK/SIRT1/p38/cPLA2 pathway.
资助项目	This work was funded by grants from National Natural Science Foundation of China (No. 82072192 to Kailiang Zhou); Wenzhou Science and Technology Bureau Foundation (No. Y20210438 to Kailiang Zhou); Zhejiang Province Public Welfare Technology Application Res [82072192]; National Natural Science Foundation of China [Y20210438]; Wenzhou Science and Technology Bureau Foundation [LGF20H150003]; Zhejiang Province Public Welfare Technology Application Research Project [LY21H060009]; Natural Science Foundation of Zhejiang Province
出版者	WILEY
ISSN	0007-1188
EISSN	1476-5381
卷号	181 期号:5 页码:712-734
DOI	10.1111/bph.16255
页数	23
WOS类目	Pharmacology & Pharmacy
WOS研究方向	Pharmacology & Pharmacy
WOS记录号	WOS:001090770400001
收录类别	PUBMED ; SCIE ; SCOPUS
URL	查看原文
PubMed ID	37766498
SCOPUSEID	2-s2.0-85174585698
通讯作者地址	[Ni, Wenfei]Department of Orthopaedics,The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University,Wenzhou,China ; [Zhou, Kailiang]Department of Orthopaedics,The Second Affiliated Hospital,Yuying Children's Hospital of Wenzhou Medical University,109 West Xueyuan Road, Zhejiang,Wenzhou,325000,China ; [Xiao, Jian]School of Pharmaceutical Sciences,Wenzhou Medical University,Zhejiang,Wenzhou,325035,China
Scopus学科分类	Pharmacology
引用统计
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/183272
专题	药学院（分析测试中心）附属第二医院第二临床医学院、附属第二医院、育英儿童医院研究生工作部（研究生院）其他_温州医科大学慈溪生物医药研究院
通讯作者	Xiao, Jian; Ni, Wenfei; Zhou, Kailiang
作者单位	1.Department of Orthopaedics,The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University,Wenzhou,China; 2.Zhejiang Provincial Key Laboratory of Orthopaedics,Wenzhou,China; 3.The Second Clinical Medical College of Wenzhou Medical University,Wenzhou,China; 4.Cixi Biomedical Research Institute,Wenzhou Medical University,Ningbo,China; 5.School of Pharmaceutical Sciences,Wenzhou Medical University,Wenzhou,China
第一作者单位	第二临床医学院，附属第二医院、育英儿童医院; 附属第二医院
通讯作者单位	第二临床医学院，附属第二医院、育英儿童医院; 附属第二医院; 药学院（分析测试中心）
第一作者的第一单位	第二临床医学院，附属第二医院、育英儿童医院
推荐引用方式 GB/T 7714	Chen, Yituo,Zhang, Haojie,Jiang, Liting,et al. DADLE promotes motor function recovery by inhibiting cytosolic phospholipase A2 mediated lysosomal membrane permeabilization after spinal cord injury[J]. British journal of pharmacology,2023,181(5):712-734.
APA	Chen, Yituo., Zhang, Haojie., Jiang, Liting., Cai, Wanta., Kuang, Jiaxuan., ... & Zhou, Kailiang. (2023). DADLE promotes motor function recovery by inhibiting cytosolic phospholipase A2 mediated lysosomal membrane permeabilization after spinal cord injury. British journal of pharmacology, 181(5), 712-734.
MLA	Chen, Yituo,et al."DADLE promotes motor function recovery by inhibiting cytosolic phospholipase A2 mediated lysosomal membrane permeabilization after spinal cord injury".British journal of pharmacology 181.5(2023):712-734.