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 obj...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.展开更多
基金supported by the Zhuhai Science and Technology Plan(ZH22036201210174PWC).
文摘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.
