PMID- 33039524 OWN - NLM STAT- MEDLINE DCOM- 20210514 LR - 20210514 IS - 1873-7544 (Electronic) IS - 0306-4522 (Linking) VI - 451 DP - 2020 Dec 15 TI - A New Therapeutic Strategy Targeting Protein Deacetylation for Spinal Cord Injury. PG - 197-206 LID - S0306-4522(20)30650-3 [pii] LID - 10.1016/j.neuroscience.2020.09.060 [doi] AB - Lysine acetylation is a post-translational modification that regulates a diversity of biological processes. However, its implication in spinal cord injury (SCI) remains unclear. Here we investigated the acetylation events in injured spinal cords on a proteomic scale for the first time. Additionally, whether promoting acetylation could mitigate SCI was evaluated. A total of 268 differentially acetylated peptides were identified. Among them, 2 peptides were up-acetylated and 141 peptides were down-acetylated in the injured spinal cord tissues (Fold change >2 and P < 0.05). There were also 116 unique acetylated peptides in the sham group and 9 unique acetylated peptides in the SCI group. Functional enrichment analysis revealed that differently acetylated proteins were involved in multiple cellular processes and metabolic processes. Kyoto Encyclopaedia of Genes and Genomes analysis showed that several pathways, including cGMP-PKG signaling pathway and hypoxia-inducible factor-1 (HIF-1) signaling pathway, were predominantly presented. Moreover, promoting acetylation using glycerol triacetate (GTA) showed a therapeutic effect on SCI, with improved Basso-Beattie-Bresnahan scores and histologic morphology, and decreased neuronal apoptosis and inflammation. In conclusion, our data indicated that protein deacetylation might play crucial roles in the development of secondary injury of SCI, and promoting acetylation by GTA effectively mitigated SCI. Our data not only enhance our understanding on acetylproteome dataset in the spinal cord tissues, but also provide novel insights for the treatment of SCI. CI - Copyright (c) 2020 IBRO. Published by Elsevier Ltd. All rights reserved. FAU - Liu, Xinwei AU - Liu X AD - Department of Orthopaedics, the General Hospital of Northern Theater Command, Shenyang 110016, People's Republic of China. FAU - Ma, Bin AU - Ma B AD - Division of Spine Surgery, Department of Orthopaedics, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, People's Republic of China. FAU - Zhang, Haocong AU - Zhang H AD - Department of Orthopaedics, the General Hospital of Northern Theater Command, Shenyang 110016, People's Republic of China. FAU - Chai, Ruonan AU - Chai R AD - Department of Respiratory Medicine, the General Hospital of Northern Theater Command, Shenyang 110016, People's Republic of China. Electronic address: lilypad_ff@126.com. FAU - Xiang, Liangbi AU - Xiang L AD - Department of Orthopaedics, the General Hospital of Northern Theater Command, Shenyang 110016, People's Republic of China. Electronic address: deformitya@126.com. LA - eng PT - Journal Article DEP - 20201009 PL - United States TA - Neuroscience JT - Neuroscience JID - 7605074 SB - IM MH - Acetylation MH - Humans MH - *Proteomics MH - Signal Transduction MH - Spinal Cord MH - *Spinal Cord Injuries/drug therapy OTO - NOTNLM OT - acetylome OT - glycerol triacetate OT - lysine acetylation OT - spinal cord injury EDAT- 2020/10/12 06:00 MHDA- 2021/05/15 06:00 CRDT- 2020/10/11 20:23 PHST- 2020/04/14 00:00 [received] PHST- 2020/09/27 00:00 [revised] PHST- 2020/09/29 00:00 [accepted] PHST- 2020/10/12 06:00 [pubmed] PHST- 2021/05/15 06:00 [medline] PHST- 2020/10/11 20:23 [entrez] AID - S0306-4522(20)30650-3 [pii] AID - 10.1016/j.neuroscience.2020.09.060 [doi] PST - ppublish SO - Neuroscience. 2020 Dec 15;451:197-206. doi: 10.1016/j.neuroscience.2020.09.060. Epub 2020 Oct 9.