新型程序性细胞死亡方式——焦亡的研究进展
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摘要
细胞死亡包括程序性死亡及坏死,而程序性死亡中新型的细胞死亡方式——焦亡被发现,更新了人们对细胞死亡的认识。近年来,细胞焦亡机制的研究取得重大进展,研究显示Gasdermin家族蛋白是焦亡的直接执行者,其中重要成员Gasdermin D和Gasdermin E的上游信号蛋白也基本明确。细胞焦亡时,Gasdermin蛋白N端域插入细胞膜形成孔道,导致细胞膜破裂,细胞内容物外渗,并释放IL-1β和IL-18。焦亡作为区别于凋亡的新型细胞程序性死亡,具有诱导炎性反应的特征。因此深入研究焦亡在疾病中的作用与机制,对阐明炎性相关疾病的机制和指导治疗具有重要意义。本文就焦亡的发现、焦亡通路的信号蛋白及在相关疾病的研究进展作一概述。
Cell death includes programmed death and necrosis. When a new type of programmed cell death—pyroptosis was found, it updated the understanding of cell death. Recent studies of the mechanism of cell death pyroptosis made significant progress which found Gasdermin family proteins is a direct executor of pyroptosis. And the upstream signaling proteins of the important members:Gasdermin D and Gasdermin E are basically clear. Gasdermin N-terminal domainsinsert into the cell membrane to form a pore, leading to rupture of the cell membrane, extravasation of cellular contents, and release of IL-1β and IL-18. As a new type of programmed cell death that is different from apoptosis, pyroptosis is characterized by the induction of inflammatory reactions. Therefore, the in-depth study of the role and mechanism of pyroptosis in diseases is of great significance for elucidating the mechanisms of inflammatory diseases and guiding treatment. This article provides an overview of the discovery of pyroptosis, the signaling proteins of pyroptosis pathway, and the research progress in related diseases.
Cell death includes programmed death and necrosis. When a new type of programmed cell death—pyroptosis was found, it updated the understanding of cell death. Recent studies of the mechanism of cell death pyroptosis made significant progress which found Gasdermin family proteins is a direct executor of pyroptosis. And the upstream signaling proteins of the important members:Gasdermin D and Gasdermin E are basically clear. Gasdermin N-terminal domainsinsert into the cell membrane to form a pore, leading to rupture of the cell membrane, extravasation of cellular contents, and release of IL-1β and IL-18. As a new type of programmed cell death that is different from apoptosis, pyroptosis is characterized by the induction of inflammatory reactions. Therefore, the in-depth study of the role and mechanism of pyroptosis in diseases is of great significance for elucidating the mechanisms of inflammatory diseases and guiding treatment. This article provides an overview of the discovery of pyroptosis, the signaling proteins of pyroptosis pathway, and the research progress in related diseases.
引文
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[9]F Martinon,K Burns,J Tschopp.The Inflammasome:A Molecular Platform Triggering Activation of Inflammatory Caspases and Processing of Proil-Beta[J].Mol Cell,2002,10(2):417-426
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[15]J Shi,Y Zhao,Y Wang,et al.Inflammatory Caspases Are Innate Immune Receptors for Intracellular Lps[J].Nature,2014,514(7521):187-192
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[17]N Saeki,T Usui,K Aoyagi,et al.Distinctive Expression and Function of Four Gsdm Family Genes(Gsdma-D)in Normal and Malignant Upper Gastrointestinal Epithelium[J].Genes Chromosomes Cancer,2009,48(3):261-271
[18]J Ding,K Wang,W Liu,et al.Pore-Forming Activity and Structural Autoinhibition of the Gasdermin Family[J].Nature,2016,535(7610):111-116
[19]Y Wang,W Gao,X Shi,et al.Chemotherapy Drugs Induce Pyroptosis through Caspase-3 Cleavage of a Gasdermin[J].Nature,2017,547(7661):99-103
[20]S M Man,T D Kanneganti.Gasdermin D:The Long-Awaited Executioner of Pyroptosis[J].Cell Res,2015,25(11):1183-1184
[21]S M Man,T D Kanneganti.Regulation of Inflammasome Activation[J].Immunol Rev,2015,265(1):6-21
[22]J Shi,W Gao,F Shao.Pyroptosis:Gasdermin-Mediated Programmed Necrotic Cell Death[J].Trends Biochem Sci,2017,42(4):245-254
[23]T Bergsbaken,S L Fink,B T Cookson.Pyroptosis:Host Cell Death and Inflammation[J].Nat Rev Microbiol,2009,7(2):99-109
[24]J Y Kim,J C Paton,D E Briles,et al.Streptococcus Pneumoniae Induces Pyroptosis through the Regulation of Autophagy in Murine Microglia[J].Oncotarget,2015,6(42):44161-44178
[25]S Accarias,G Lugo-Villarino,G Foucras,et al.Pyroptosis of Resident Macrophages Differentially Orchestrates Inflammatory Responses to Staphylococcus Aureus in Resistant and Susceptible Mice[J].Eur JImmunol,2015,45(3):794-806
[26]S L Fink,B T Cookson.Pyroptosis and Host Cell Death Responses During Salmonella Infection[J].Cell Microbiol,2007,9(11):2562-2570
[27]B Martina,M Smreczak,A Orlowska,et al.Combination Drug Treatment Prolongs Survival of Experimentally Infected Mice with SilverHaired Bat Rabies Virus[J].Vaccine,2018
[28]Y Wang,Y Qin,T Wang,et al.Pyroptosis Induced by Enterovirus 71and Coxsackievirus B3 Infection Affects Viral Replication and Host Response[J].Sci Rep,2018,8(1):2887
[29]K Cheung,D Sze,K Chan,et al.Involvement of Caspase-4 in Il-1Beta Production and Pyroptosis in Human Macrophages During Dengue Virus Infection[J].Immunobiology,2018,223(4-5):356-364
[30]S Sarvestani,J Mcauley.The Role of the Nlrp3 Inflammasome in Regulation of Antiviral Responses to Influenza a Virus Infection[J].Antiviral Res,2017,148:32-42
[31]X Deng,W Zou,M Xiong,et al.Human Parvovirus Infection of Human Airway Epithelia Induces Pyroptotic Cell Death by Inhibiting Apoptosis[J].J Virol,2017,91(24)
[32]D So,H Shin,J Kim,et al.Cervical Cancer Is Addicted to Sirt1 Disarming the Aim2 Antiviral Defense[J].Oncogene,2018
[33]F Wang,W Liu,J Ning,et al.Simvastatin Suppresses Proliferation and Migration in Non-Small Cell Lung Cancer Via Pyroptosis[J].Int.J.Biol.Sci,2018,14(4):406-417
[34]N Pizato,B Luzete,L Kiffer,et al.Omega-3 Docosahexaenoic Acid Induces Pyroptosis Cell Death in Triple-Negative Breast Cancer Cells[J].Sci Rep,2018,8(1):1952
[35]Y Wang,B Yin,D Li,et al.Gsdme Mediates Caspase-3-Dependent Pyroptosis in Gastric Cancer[J].Biochem Biophys Res Commun,2018,495(1):1418-1425
[36]J Li,C Yang,Y Li,et al.Lncrna Gas5 Suppresses Ovarian Cancer by Inducing Inflammasome Formation[J].Biosci.Rep,2017
[37]M S Tan,L Tan,T Jiang,et al.Amyloid-Beta Induces Nlrp1-Dependent Neuronal Pyroptosis in Models of Alzheimer's Disease[J].Cell Death Dis,2014,5:e1382
[38]C C Tan,J G Zhang,M S Tan,et al.Nlrp1 Inflammasome Is Activated in Patients with Medial Temporal Lobe Epilepsy and Contributes to Neuronal Pyroptosis in Amygdala Kindling-Induced Rat Model[J].JNeuroinflammation,2015,12:18
[39]M Tang,X Li,P Liu,et al.Bradykinin B2 Receptors Play a Neuroprotective Role in Hypoxia/Reoxygenation Injury Related to Pyroptosis Pathway[J].Curr Neurovasc Res,2018
[40]J Rojas,V Bermudez,J Palmar,et al.Pancreatic Beta Cell Death:Novel Potential Mechanisms in Diabetes Therapy[J].J Diabetes Res,2018,2018:9601801
[41]Y Han,H Qiu,X Pei,et al.Low-Dose Sinapic Acid Abates the Pyroptosis of Macrophages by Downregulation of Lncrna-Malat1 in Rats with Diabetic Atherosclerosis[J].J Cardiovasc Pharmacol,2018,71(2):104-112
[42]X Wu,H Zhang,W Qi,et al.Nicotine Promotes Atherosclerosis Via Ros-Nlrp3-Mediated Endothelial Cell Pyroptosis[J].Cell Death Dis,2018,9(2):171
[43]J R Yang,F H Yao,J G Zhang,et al.Ischemia-Reperfusion Induces Renal Tubule Pyroptosis Via the Chop-Caspase-11 Pathway[J].Am JPhysiol Renal Physiol,2014,306(1):F75-84
[44]Z Qiu,S Lei,B Zhao,et al.Nlrp3 Inflammasome Activation-Mediated Pyroptosis Aggravates Myocardial Ischemia/Reperfusion Injury in Diabetic Rats[J].Oxid Med Cell Longev,2017,2017:9743280
[2]H Liang,Y Liu.Gasdermins Pore Cell Membrane to Pyroptosis[J].Sci China Life Sci,2016,59(10):1090-1092
[3]S Shalini,L Dorstyn,S Dawar,et al.Old,New and Emerging Functions of Caspases[J].Cell Death Differ,2015,22(4):526-539
[4]J Shi,Y Zhao,K Wang,et al.Cleavage of Gsdmd by Inflammatory Caspases Determines Pyroptotic Cell Death[J].Nature,2015,526(7575):660-665
[5]A Zychlinsky,M C Prevost,P J Sansonetti.Shigella Flexneri Induces Apoptosis in Infected Macrophages[J].Nature,1992,358(6382):167-169
[6]A Zychlinsky,C Fitting,J M Cavaillon,et al.Interleukin 1 Is Released by Murine Macrophages During Apoptosis Induced by Shigella Flexneri[J].J Clin Invest,1994,94(3):1328-1332
[7]B T Cookson,M A Brennan.Pro-Inflammatory Programmed Cell Death[J].Trends Microbiol,2001,9(3):113-114
[8]L Galluzzi,I Vitale,J M Abrams,et al.Molecular Definitions of Cell Death Subroutines:Recommendations of the Nomenclature Committee on Cell Death 2012[J].Cell Death Differ,2012,19(1):107-120
[9]F Martinon,K Burns,J Tschopp.The Inflammasome:A Molecular Platform Triggering Activation of Inflammatory Caspases and Processing of Proil-Beta[J].Mol Cell,2002,10(2):417-426
[10]G Y Chen,G Nuez.Sterile Inflammation:Sensing and Reacting to Damage[J].Nat Rev Immunol,2010,10(12):826-837
[11]H Guo,J B Callaway,J P Ting.Inflammasomes:Mechanism of Action,Role in Disease,and Therapeutics[J].Nat Med,2015,21(7):677-687
[12]J Von Moltke,J S Ayres,E M Kofoed,et al.Recognition of Bacteria by Inflammasomes[J].Annu Rev Immunol,2013,31:73-106
[13]T Jin,A Perry,J Jiang,et al.Structures of the Hin Domain:DNAComplexes Reveal Ligand Binding and Activation Mechanisms of the Aim2 Inflammasome and Ifi16 Receptor[J].Immunity,2012,36(4):561-571
[14]E A Miao,J V Rajan,A Aderem.Caspase-1-Induced Pyroptotic Cell Death[J].Immunol Rev,2011,243(1):206-214
[15]J Shi,Y Zhao,Y Wang,et al.Inflammatory Caspases Are Innate Immune Receptors for Intracellular Lps[J].Nature,2014,514(7521):187-192
[16]R A Aglietti,E C Dueber.Recent Insights into the Molecular Mechanisms Underlying Pyroptosis and Gasdermin Family Functions[J].Trends Immunol,2017,38(4):261-271
[17]N Saeki,T Usui,K Aoyagi,et al.Distinctive Expression and Function of Four Gsdm Family Genes(Gsdma-D)in Normal and Malignant Upper Gastrointestinal Epithelium[J].Genes Chromosomes Cancer,2009,48(3):261-271
[18]J Ding,K Wang,W Liu,et al.Pore-Forming Activity and Structural Autoinhibition of the Gasdermin Family[J].Nature,2016,535(7610):111-116
[19]Y Wang,W Gao,X Shi,et al.Chemotherapy Drugs Induce Pyroptosis through Caspase-3 Cleavage of a Gasdermin[J].Nature,2017,547(7661):99-103
[20]S M Man,T D Kanneganti.Gasdermin D:The Long-Awaited Executioner of Pyroptosis[J].Cell Res,2015,25(11):1183-1184
[21]S M Man,T D Kanneganti.Regulation of Inflammasome Activation[J].Immunol Rev,2015,265(1):6-21
[22]J Shi,W Gao,F Shao.Pyroptosis:Gasdermin-Mediated Programmed Necrotic Cell Death[J].Trends Biochem Sci,2017,42(4):245-254
[23]T Bergsbaken,S L Fink,B T Cookson.Pyroptosis:Host Cell Death and Inflammation[J].Nat Rev Microbiol,2009,7(2):99-109
[24]J Y Kim,J C Paton,D E Briles,et al.Streptococcus Pneumoniae Induces Pyroptosis through the Regulation of Autophagy in Murine Microglia[J].Oncotarget,2015,6(42):44161-44178
[25]S Accarias,G Lugo-Villarino,G Foucras,et al.Pyroptosis of Resident Macrophages Differentially Orchestrates Inflammatory Responses to Staphylococcus Aureus in Resistant and Susceptible Mice[J].Eur JImmunol,2015,45(3):794-806
[26]S L Fink,B T Cookson.Pyroptosis and Host Cell Death Responses During Salmonella Infection[J].Cell Microbiol,2007,9(11):2562-2570
[27]B Martina,M Smreczak,A Orlowska,et al.Combination Drug Treatment Prolongs Survival of Experimentally Infected Mice with SilverHaired Bat Rabies Virus[J].Vaccine,2018
[28]Y Wang,Y Qin,T Wang,et al.Pyroptosis Induced by Enterovirus 71and Coxsackievirus B3 Infection Affects Viral Replication and Host Response[J].Sci Rep,2018,8(1):2887
[29]K Cheung,D Sze,K Chan,et al.Involvement of Caspase-4 in Il-1Beta Production and Pyroptosis in Human Macrophages During Dengue Virus Infection[J].Immunobiology,2018,223(4-5):356-364
[30]S Sarvestani,J Mcauley.The Role of the Nlrp3 Inflammasome in Regulation of Antiviral Responses to Influenza a Virus Infection[J].Antiviral Res,2017,148:32-42
[31]X Deng,W Zou,M Xiong,et al.Human Parvovirus Infection of Human Airway Epithelia Induces Pyroptotic Cell Death by Inhibiting Apoptosis[J].J Virol,2017,91(24)
[32]D So,H Shin,J Kim,et al.Cervical Cancer Is Addicted to Sirt1 Disarming the Aim2 Antiviral Defense[J].Oncogene,2018
[33]F Wang,W Liu,J Ning,et al.Simvastatin Suppresses Proliferation and Migration in Non-Small Cell Lung Cancer Via Pyroptosis[J].Int.J.Biol.Sci,2018,14(4):406-417
[34]N Pizato,B Luzete,L Kiffer,et al.Omega-3 Docosahexaenoic Acid Induces Pyroptosis Cell Death in Triple-Negative Breast Cancer Cells[J].Sci Rep,2018,8(1):1952
[35]Y Wang,B Yin,D Li,et al.Gsdme Mediates Caspase-3-Dependent Pyroptosis in Gastric Cancer[J].Biochem Biophys Res Commun,2018,495(1):1418-1425
[36]J Li,C Yang,Y Li,et al.Lncrna Gas5 Suppresses Ovarian Cancer by Inducing Inflammasome Formation[J].Biosci.Rep,2017
[37]M S Tan,L Tan,T Jiang,et al.Amyloid-Beta Induces Nlrp1-Dependent Neuronal Pyroptosis in Models of Alzheimer's Disease[J].Cell Death Dis,2014,5:e1382
[38]C C Tan,J G Zhang,M S Tan,et al.Nlrp1 Inflammasome Is Activated in Patients with Medial Temporal Lobe Epilepsy and Contributes to Neuronal Pyroptosis in Amygdala Kindling-Induced Rat Model[J].JNeuroinflammation,2015,12:18
[39]M Tang,X Li,P Liu,et al.Bradykinin B2 Receptors Play a Neuroprotective Role in Hypoxia/Reoxygenation Injury Related to Pyroptosis Pathway[J].Curr Neurovasc Res,2018
[40]J Rojas,V Bermudez,J Palmar,et al.Pancreatic Beta Cell Death:Novel Potential Mechanisms in Diabetes Therapy[J].J Diabetes Res,2018,2018:9601801
[41]Y Han,H Qiu,X Pei,et al.Low-Dose Sinapic Acid Abates the Pyroptosis of Macrophages by Downregulation of Lncrna-Malat1 in Rats with Diabetic Atherosclerosis[J].J Cardiovasc Pharmacol,2018,71(2):104-112
[42]X Wu,H Zhang,W Qi,et al.Nicotine Promotes Atherosclerosis Via Ros-Nlrp3-Mediated Endothelial Cell Pyroptosis[J].Cell Death Dis,2018,9(2):171
[43]J R Yang,F H Yao,J G Zhang,et al.Ischemia-Reperfusion Induces Renal Tubule Pyroptosis Via the Chop-Caspase-11 Pathway[J].Am JPhysiol Renal Physiol,2014,306(1):F75-84
[44]Z Qiu,S Lei,B Zhao,et al.Nlrp3 Inflammasome Activation-Mediated Pyroptosis Aggravates Myocardial Ischemia/Reperfusion Injury in Diabetic Rats[J].Oxid Med Cell Longev,2017,2017:9743280