Annexin A1 inhibition facilitates NLRP3 inflammasome activation in arsenic-induced insulin resistance in rat liver

  • Environ Toxicol Pharmacol. 2022 Sep 28;96:103981. doi: 10.1016/j.etap.2022.103981.
Chenbing Wu  1 ,  Tianming Qiu  2 ,  Weizhuo Yuan  3 ,  Yan Shi  4 ,  Xiaofeng Yao  5 ,  Liping Jiang  6 ,  Jingyuan Zhang  7 ,  Guang Yang  8 ,  Xiaofang Liu  9 ,  Jie Bai  10 ,  Danyi Zhao  11 ,  Xiance Sun  12
Affiliations
  • 1. Department of Occupational and Environmental Health, School of Public Health, Dalian Medical University, No. 9 West Section Lvshun South Road, Dalian 116044, PR China. Electronic address: [email protected].
  • 2. Department of Occupational and Environmental Health, School of Public Health, Dalian Medical University, No. 9 West Section Lvshun South Road, Dalian 116044, PR China. Electronic address: [email protected].
  • 3. Department of Occupational and Environmental Health, School of Public Health, Dalian Medical University, No. 9 West Section Lvshun South Road, Dalian 116044, PR China. Electronic address: [email protected].
  • 4. Department of Occupational and Environmental Health, School of Public Health, Dalian Medical University, No. 9 West Section Lvshun South Road, Dalian 116044, PR China. Electronic address: [email protected].
  • 5. Department of Occupational and Environmental Health, School of Public Health, Dalian Medical University, No. 9 West Section Lvshun South Road, Dalian 116044, PR China. Electronic address: [email protected].
  • 6. Preventive Medicine Laboratory, School of Public Health, Dalian Medical University, No. 9 West Section Lvshun South Road, 116044, PR China. Electronic address: [email protected].
  • 7. Department of Occupational and Environmental Health, School of Public Health, Dalian Medical University, No. 9 West Section Lvshun South Road, Dalian 116044, PR China. Electronic address: [email protected].
  • 8. Department of Nutrition and Food Safety, School of Public Health, Dalian Medical University, No. 9 West Section Lvshun South Road, Dalian 116044, PR China. Electronic address: [email protected].
  • 9. Department of Nutrition and Food Safety, School of Public Health, Dalian Medical University, No. 9 West Section Lvshun South Road, Dalian 116044, PR China. Electronic address: [email protected].
  • 10. Department of Nutrition and Food Safety, School of Public Health, Dalian Medical University, No. 9 West Section Lvshun South Road, Dalian 116044, PR China. Electronic address: [email protected].
  • 11. Department of Gastrointestinal Oncology, The Second Hospital of Dalian Medical University, Dalian, PR China. Electronic address: [email protected].
  • 12. Department of Occupational and Environmental Health, School of Public Health, Dalian Medical University, No. 9 West Section Lvshun South Road, Dalian 116044, PR China; Global Health Research Center, Dalian Medical University, No. 9 West Section Lvshun South Road, Dalian 116044, PR China. Electronic address: [email protected].
PMID: 36182042 DOI: 10.1016/j.etap.2022.103981
Abstract

Hepatic Insulin resistance (IR) is the primary pathology of type 2 diabetes (T2D). The role of the NOD-like Receptor protein 3 (NLRP3) inflammasome in arsenic-induced hepatic IR has been previously demonstrated. However, the mechanism of the arsenic-induced activation of the NLRP3 inflammasome is still unclear. Here, we demonstrate that NaAsO2 downregulated the mRNA and protein level of Annexin A1 (AnxA1), an anti-inflammatory factor, in rat livers and L-02 cells. Moreover, AnxA1 overexpression significantly alleviated arsenic-induced NLRP3 inflammasome activation and IR in L-02 cells. Importantly, Co-immunoprecipitation (Co-IP) results showed that AnxA1 1-190 peptide could bind to the domain encompassing Amino acids 1-210 and 211-550 of NLRP3. In conclusion, our experiments demonstrated that arsenic exposure could activate the NLRP3 inflammasome and IR by inhibiting the AnxA1 activity. These findings suggest that AnxA1 may be a promising therapeutic target of arsenicosis.

Keywords
Annexin A1; Arsenic; Insulin resistance; NLRP3; Type 2 diabetes.
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