α7nAChR inhibition by methyllycaconitine citrate promotes cell pyroptosis by triggering the polyol pathway in cervical cancer cells  

作　　者：JUNYING XU PING LI GE WANG DAQIANG YE XIUFU TANG 

机构地区：[1]Department of Gynecology,Zhuhai Women’s and Children’s Hospital,Zhuhai,519000,China [2]Institute of Genetic Research,Zhuhai Women’s and Children’s Hospital,Zhuhai,519000,China [3]Department of Pediatric Haematology and Rheumatalogy,Zhuhai Center For Maternal and Child Health Care,Zhuhai,519000,China

出　　处：《BIOCELL》2024年第2期283-291,共9页生物细胞(英文)

基　　金：supported by the Zhuhai Science and Technology Plan(ZH22036201210174PWC).

摘　　要：Background:α7 nicotinic acetylcholine receptor(α7nAChR)has been demonstrated to be involved in numerous of inflammatory diseases.Cell pyroptosis is a kind of cell death accompanied by inflammation.Objectives:The objective of this work is to explore the function ofα7nAChR on cell pyroptosis in cervical cancer cells.Methods:Immunoblotting,quantitative polymerase chain reaction,and enzyme-linked immunosorbent assay were employed to examine the function ofα7nAChR on cell pyroptosis and metabolic changes.Results:Herein,we found thatα7nAChR inhibition led to cell pyroptosis in HeLa and SiHa of cervical cancer cells,which was attributed to the upregulation of the polyol pathway.Inhibition ofα7nAChR in HeLa and SiHa cells induced the activation of NACHT,LRR and PYD domains-containing protein 3 inflammasomes,leading to enhanced cleaved caspase-1 expression to activate gasdermin D and interleukin-18/1βmature and secretion.Moreover,α7nAChR activation in cervical cancer cells decreased the aldo-keto reductase family 1 member B1(AKR1B1)-mediated polyol pathway,resulting in reduced sorbitol production.Suppression of AKR1B1 could overcome cell pyroptosis caused byα7nAChR inhibition.Mechanically,α7nAChR inhibition could increase the level of phosphorylation of nuclear factor-kappa B(NF-κB)in HeLa cells,whileα7nAChR activation caused inhibition of NF-κB phosphorylation,which further reduced NF-κB binding to the AKR1B1 promoter and consequently abolished AKR1B1 transactivation.In addition,inhibition of NF-κB activity could reverse the promotion ofα7nAChR inhibition on cell pyroptosis.Conclusion:This work enriches the metabolic function ofα7nAChR in cancer cells and reveals the novel mechanism ofα7nAChR-mediated cell pyroptosis.

关 键 词：α7nAChR Cell pyroptosis AKR1B1 NF-κB 

分 类 号：R73[医药卫生—肿瘤]