A new therapeutic strategy targeting protein deacetylation for spinal cord injury.

Lysine acetylation is a post-translational modification that regulates a diversity of biological processes. However, its implication in spinal cord injury 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 spinal cord injury 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 spinal cord injury 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 signaling pathway, were predominantly presented. Moreover, promoting acetylation using glycerol triacetate (GTA) showed a therapeutic effect on spinal cord injury, 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.