Proteomic analysis of lysine acetylation reveals that metabolic enzymes and heat shock proteins may be potential targets for DSS-induced mice colitis.

Int Immunopharmacol

Acupuncture and Moxibustion School, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 610075, China,; Acupuncture & Chronobiology Key Laboratory of Sichuan Province, No.37, Road Shi-Er-Qiao, Jinniu District, Chengdu, Sichuan 610075,China. Electronic address:

Published: December 2021

Background: Research on acetylation modification and its modification sites will be of great significance for revealing the mechanism of disease and developing new targeted medicines. In this study, we aim to construct a complete atlas of acetylome in the DSS-induced ulcerative colitis mice model (UC model) METHODS: A high-resolution mass spectrometry-based quantitative approach was employed to identify lysine-acetylated proteins and acetylation sites. Bioinformatics analysis and in vitro experiments verified anti-inflammatory effects of HSP90B1-K142ac.

Results: 2597 acetylation events and 1914 sites were quantified, highlighting 140 acetylation site changes in the colitis colon tissue. 91 acetylation sites in 75 proteins were up-regulated, and 49 acetylation sites in 39 proteins were down-regulated in the UC models. The differentially acetylated proteins mainly consisted of non-histone proteins located in the cytoplasm and mitochondria. KEGG and protein-protein interaction networks analysis showed that the differentially acetylated proteins were enriched in the TCA cycle, fatty acid metabolism, and protein processing in the endoplasmic reticulum. 68% of the differentially metabolized enzymes have a down-regulated trend in acetylation levels. The acetylation level of lysine 142 in HSP90B1 was found to be obvious in the UC colon, and point mutation of HSP90B1-K142ac would result in the decreasing secretion of TNF-α and IL-2 in LPS-stimulated cultured cells.

Conclusion: Our work built a complete atlas of acetylome and revealed the potential role of metabolic enzymes and heat shock proteins in DSS-induced colitis.

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http://dx.doi.org/10.1016/j.intimp.2021.108336DOI Listing

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