摘要
缺血心肌恢复血流灌注后,心肌细胞会因血流再灌注产生额外的损伤,称之为心肌缺血再灌注损伤。细胞程序性死亡是心肌缺血再灌注损伤的主要细胞归宿,减少细胞程序性死亡能改善患者的心功能和预后。细胞程序性死亡包括凋亡、自噬和程序性坏死,cFLIP可通过不同的方式分别调控凋亡、自噬与程序性坏死的发生,调节心肌缺血再灌注损伤。
After the ischemic myocardium resumes blood perfusion,the cardiomyocytes will cause additional damage due to reperfusion of blood flow,which is called myocardial ischemia-reperfusion injury.Programmed cell death is the main cell destination of myocardial ischemia-reperfusion injury and reducing programmed cell death can improve cardiac function and prognosis.Programmed cell death includes apoptosis,autophagy and programmed necrosis.cFLIP can regulate apoptosis,autophagy and programmed necrosis in different ways to regulate myocardial ischemia-reperfusion injury.
引文
[1]Ibáez B,Heusch G,Ovize M,et al.Evolving therapies for myocardial ischemia/reperfusion injury[J].J Am Coll Cardiol,2015,65(14):1454-1471.
[2]Safa AR.Roles of c-FLIP in apoptosis,necroptosis,and autophagy[J].J Carcinog Mutagen,2013,Suppl6.pii:003.
[3]Safa AR.c-FLIP,A master anti-apoptotic regulator[J].Exp Oncol,2012,34(3):176-184.
[4]Poukkula M,Kaunisto A,Hietakangas V,et al.Rapid turnover of c-FLIP short is determined by its unique C-terminal tail[J].J Biol Chem,2005,280(29):27345-27355.
[5]Zhu H,Sun A.Programmed necrosis in heart disease:Molecular mechanisms and clinical implications[J].JMol Cell Cardiol,2018,116:125-134.
[6]Ma S,Wang Y,Chen Y,et al.The role of the autophagy in myocardial ischemia/reperfusion injury[J].Biochim Biophys Acta,2015,1852(2):271-276.
[7]Zhu L,Wei T,Gao J,et al.The cardioprotective effect of salidroside against myocardial ischemia reperfusion injury in rats by inhibiting apoptosis and inflammation[J].Apoptosis,2015,20(11):1433-1443.
[8]Imanishi T,Mcbride J,Ho Q,et al.Expression of cellular FLICE-inhibitory protein in human coronary arteries and in a rat vascular injury model[J].Am JPathol,2000,156(1):125-137.
[9]Stein AB,Bolli R,Guo Y,et al.The late phase of ischemic preconditioning induces a prosurvival genetic program that results in marked attenuation of apoptosis[J].J Mol Cell Cardiol,2007,42(6):1075-1085.
[10]Safa AR,Pollok KE.Targeting the anti-apoptotic protein c-FLIP for cancer therapy[J].Cancers,2011,3(2):1639-1671.
[11]Djeda B,Albert G,Cornelia P,et al.Increased cFLIPexpression in thymic epithelial tumors blocks autophagy via NF-κB signalling[J].Oncotarget,2017,8(52):89580-89594.
[12]Ranjan K,Pathak C.FADD regulates NF-κB activation and promotes ubiquitination of cFLIPL to induce apoptosis[J].Sci Rep,2016,6:22787.
[13]Guo W,Liu X,Li J,et al.Prdx1alleviates cardiomyocyte apoptosis through ROS-activated MAPK pathway during myocardial ischemia/reperfusion injury[J].Int J Biologic Macromol,2018,112:608-615.
[14]Wilkie-Grantham RP,Matsuzawa S,Reed JC.Novel phosphorylation and ubiquitination sites regulate reactive oxygen species-dependent degradation of anti-apoptotic c-FLIP protein[J].J Biologic Chem,2013,288(18):12777-12790.
[15]Tsuchiya Y,Nakabayashi O,Nakano H.FLIP the switch:regulation of apoptosis and necroptosis by cFLIP[J].Int J Mol Sci,2015,16(12):30321-30341.
[16]Marini ES,Giampietri C,Petrungaro S,et al.The endogenous caspase-8inhibitor c-FLIPL regulates ERmorphology and crosstalk with mitochondria[J].Cell Death Differ,2014,22(7):1131-1143.
[17]Edlich F.BCL-2proteins and apoptosis:Recent insights and unknowns[J].Biochem Biophys Res Commun,2018,500(1):26-34.
[18]He M,He Y.c-FLIP protects T lymphocytes from apoptosis in the intrinsic pathway[J].J Immunol,2015,194(7):3444-3451.
[19]Ranjan K,Pathak C.Expression of cFLIPL determines the basal interaction of Bcl-2with beclin-1and regulates p53dependent ubiquitination of Beclin-1during autophagic stress[J].J Cell Biochem,2015,117(8):1757-1768.
[20]Tsapras P,Nezis IP.Caspase involvement in autophagy[J].Cell Death Differ,2017,24(8):1369-1379.
