Annexin A1 inhibition facilitates NLRP3 inflammasome activation in arsenic-induced insulin resistance in rat liver |
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| Affiliation: | 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;2. Preventive Medicine Laboratory, School of Public Health, Dalian Medical University, No. 9 West Section Lvshun South Road, 116044, PR China;3. Department of Nutrition and Food Safety, School of Public Health, Dalian Medical University, No. 9 West Section Lvshun South Road, Dalian 116044, PR China;4. Global Health Research Center, Dalian Medical University, No. 9 West Section Lvshun South Road, Dalian 116044, PR China;5. Department of Gastrointestinal Oncology, The Second Hospital of Dalian Medical University, Dalian, PR China;1. Division of Pulmonary and Critical Care Medicine, Department of Medicine, Pennsylvania State University, College of Medicine, Hershey, PA, USA;2. Beckman Laser Institute and Medical Clinic, University of California, Irvine, CA, USA;3. Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of California, Irvine, CA, USA;4. Department of Emergency Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA;5. Rocky Mountain Poison and Drug Center, Denver Health and Hospital Authority, Denver, CO, USA;6. Department of Medicine, University of California, San Diego, La Jolla, CA, USA;7. Heart and Vascular Institute, Department of Medicine, Pennsylvania State University, College of Medicine, Hershey, PA, USA;1. Department of Biochemistry, Faculty of Science, Mahidol University, Bangkok Thailand;2. Department of Pathobiology, Faculty of Science, Mahidol University, Bangkok Thailand;1. Institute of Pharmacy and Molecular Biotechnology, Ruprecht-Karls-University, Im Neuenheimer Feld 329, 69120 Heidelberg, Germany;2. A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio 70211, Finland;3. Department of Environmental and Biological Sciences, University of Eastern Finland, Kuopio 70211, Finland;4. School of Pharmacy, University of Eastern Finland, P.O. Box 1627, 70211 Kuopio, Finland;1. Department of Toxicology and Forensic Medicine, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt;2. Department of Biochemistry and Metabolism, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt;3. Department of Pathology, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt;1. Department of Pharmaceutical Toxicology, Faculty of Pharmacy, Erciyes University, Kayseri, Turkey;2. Betül-Ziya Eren Genome and Stem Cell Center, Erciyes University, Kayseri, Turkey;3. Department of Medical Biology, Faculty of Medicine, Erciyes University, Kayseri, Turkey;4. Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden;5. Department of Pharmaceutical Toxicology, Faculty of Pharmacy, Hacettepe University, Ankara, Turkey;1. Academic of Chemical Engineering, Universidade Tecnológica Federal do Paraná (UTFPR), Campus Francisco Beltrão, Paraná, Brazil;2. Academic Department of Agricultural Sciences, Universidade Tecnológica Federal do Paraná (UTFPR), Campus Francisco Beltrão, Francisco Beltrão, Paraná, Brazil;3. Academic Department of Physics, Statistics and Mathematics, Universidade Tecnológica Federal do Paraná (UTFPR), Francisco Beltrão, Paraná, Brazil;4. Academic Department of Engineering, Universidade Tecnológica Federal do Paraná (UTFPR), Campus Francisco Beltrão, Francisco Beltrão, Paraná, Brazil;5. Academic Department of Chemistry and Biology, Universidade Tecnológica Federal do Paraná (UTFPR), Campus Francisco Beltrão, Paraná, Brazil |
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| 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. |
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| Keywords: | Arsenic Insulin resistance Type 2 diabetes NLRP3 Annexin A1 |
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