2. Academic Validation
  3. Aspirin-Mediated Acetylation of SIRT1 Maintains Intestinal Immune Homeostasis

Aspirin-Mediated Acetylation of SIRT1 Maintains Intestinal Immune Homeostasis

  • Adv Sci (Weinh). 2024 Mar 14:e2306378. doi: 10.1002/advs.202306378.
Liangguo Xie 1,  Chaoqun Li 1,  Chao Wang 1,  Zhen Wu 1,  Changchun Wang 1,  Chunyu Chen 1,  Xiaojian Chen 2,  Dejian Zhou 1,  Qiang Zhou 3,  Ping Lu 3,  Chen Ding 1,  Chen-Ying Liu 2,  Jinzhong Lin 1,  Xumin Zhang 1,  Xiaofei Yu 1,  Wei Yu 1
Affiliations

Affiliations

  • 1 State Key Laboratory of Genetic Engineering, School of Life Sciences, Zhongshan Hospital, Fudan University, Shanghai, China.
  • 2 Department of Colorectal and Anal Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • 3 Department of Research Center for Molecular Recognition and Synthesis, Department of Chemistry, Fudan University, Shanghai, China.
PMID: 38482749 DOI: 10.1002/advs.202306378
Abstract

Aspirin, also named acetylsalicylate, can directly acetylate the side-chain of lysine in protein, which leads to the possibility of unexplained drug effects. Here, the study used isotopic-labeling aspirin-d3 with mass spectrometry analysis to discover that aspirin directly acetylates 10 HDACs proteins, including SIRT1, the most studied NAD+ -dependent deacetylase. SIRT1 is also acetylated by aspirin in vitro. It is also identified that aspirin directly acetylates lysine 408 of SIRT1, which abolishes SIRT1 deacetylation activity by impairing the substrates binding affinity. Interestingly, the lysine 408 of SIRT1 can be acetylated by CBP acetyltransferase in cells without aspirin supplement. Aspirin can inhibit SIRT1 to increase the levels of acetylated p53 and promote p53-dependent Apoptosis. Moreover, the knock-in mice of the acetylation-mimic mutant of SIRT1 show the decreased production of pro-inflammatory cytokines and maintain intestinal immune homeostasis. The study indicates the importance of the acetylated internal functional site of SIRT1 in maintaining intestinal immune homeostasis.

Keywords

SIRT1 deacetylase; acetylation modification; apoptosis; aspirin; intestinal immune homeostasis.

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