内质网氧化应激与自噬在脑缺血-再灌注损伤
摘要
缺血性卒中是一种破坏性脑血管病,已成为世界范围内死亡和发病的主要原因。脑缺血-再灌注损伤被定义为缺血脑组织中引起恶化效应的生化级联反应,损害和拮抗再通的有益作用[1-3]。内质网(ER)是一种多功能细胞器,是细胞主要的钙储存库,内质网也是蛋白质折叠等场所。能量、钙离子失衡、机体氧化还原状态改变等病理情况都可破坏ER的自我平衡能力,引起蛋白错误折叠,进而激活一系列信号途径,共同称为未折叠蛋白反应(unfolded Protein rePose,UPR)。分子伴侣的诱导,错误折叠蛋白的降解,蛋白质翻译抑制是UPR的特征性改变。UPR在细胞内环境稳定过程中起关键作用。然而持续过强的UPR反应会引起内质网应激(ER应激),导致细胞凋亡的发生[4]。自噬是细胞清除胞内错误折叠的蛋白质或受损细胞器,维持内环境稳态的重要方式。ER应激是脑缺血再灌注损伤过程中一个重要步骤。ER应激的早期反应是为了恢复ER内环境稳定,持续长时间ER应激对细胞有害。脑缺血再灌注后ER应激的修饰具有明确的保护作用,使得脑缺血卒中病人有了新的治疗思路。本综述的总体目标是描述内质网氧化应激与自噬导致缺血再灌损伤损伤和未来针对性治疗提供理论基础。
引文
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[12]Chen JC,Wu ML,Huang KC,Lin WW.HMG-CoAreductase inhibitors activate the unfolded Protein resPonse and induce cytoProtective GRP78 exPression.Cardiovasc Res.2008;80:138-150.
[13]Divald A,Kivity S,Wang P,Hochhauser E,Roberts B,Teichberg S,Gomes AV,Powell SR.Myocardial ischemic Preconditioning Preserves Postischemic function of the 26S Proteasome through diminished oxidative damage to 19S regulatory Particle subunits.Circ Res.2010;106:1829-1838.
[14]Terai K,Hiramoto Y,Masaki M,Sugiyama S,Kuroda T,Hori M,Kawase I,Hirota H.AMP-activated Protein kinase Protects cardiomyocytes against hyPoxic injury through attenuation of endoPlasmic reticulum stress.Mol Cell Biol.2005;25:9554-9575.
[15]ComPr Physiol.Author manuscriPt;available in PMC2017 Oct 19.Published in final edited form as:ComPr Physiol.2016 Dec 6,7(1):113-170.
[2]Aronowski J.,Strong R.,Grotta J.C.RePerfusion injury:demonstration of brain damage Produced by rePerfusion after transient focal ischemia in rats.Journal of Cerebral Blood Flow&Metabolism.1997;17(10):1048-1056.
[3]Pan J.,Konstas A.A.,Bateman B.,Ortolano G.A.,Pile-SPellman J.RePerfusion injury following cerebral ischemia:PathoPhysiology,MR imaging,and Potential theraPies.Neuroradiology.2007;49(2):93-102.
[4]Szegezdi E,Logue SE,Gorman AM,et al.Mediations of endoPlasmic reticulum stress-induced aPoPtosis[J].EMBOReP,2006,SeP;7(9):880-885.
[5]Cardinal J,Pan P,Tsung A.Protective role of cisPlatin in ischemic liver injury through induction of autoPhagy AutoPhagy.2009;5:1211-2.
[6]Takagi H,Matsui Y,Hirotani S,Sakoda H,Asano T,Sadoshima J.AMPK mediates autoPhagy during myocardia ischemia in vivo.AutoPhagy.2007,3:405-407.
[7]Carloni S,Girelli S,ScoPa C,Buonocore G,Longini M,Balduini W.Activation of autoPhagy and Akt/CREBsignaling Play an equivalent role in the neuroProtective effect of raPamycin in neonatal hyPoxiaischemia AutoPhagy,2010,6:366-77.
[8]Huang C,Liu W,Perry CN,Yitzhaki S,Lee Y,Yuan H,Tsukada YT,Hamacher-Brady A,Mentzer RM,Jr,Gottlieb RA.AutoPhagy and Protein kinase Care required for cardioProtection by sulfaPhenazole.Am JPhysiol Heart Circ Physiol.2010;298:H570-579.
[9]Minamino T,Komuro I,Kitakaze M.EndoPlasmic reticulum stress as a theraPeutic target in cardiovascular disease.Circ Res.2010;107:1071-1082.
[10]Belmont PJ,Chen WJ,San Pedro MN,Thuerauf DJ,Gellings Lowe N,Gude N,Hilton B,Wolkowicz R,Sussman MA,Glembotski CC.Roles for endoPlasmic reticulum-associated degradation and the novel endoPlasmic reticulum stress resPonse gene Derlin-3 in the ischemic heart.Circ Res.2010;106:307-316.
[11]Tadimalla A,Belmont PJ,Thuerauf DJ,Glassy MS,Martindale JJ,Gude N,Sussman MA,Glembotski CC.MesencePhalic astrocyte-derived neurotroPhic factor is an ischemia-inducible secreted endoPlasmic reticulum stress resPonse Protein in the heart.Circ Res,2008;103:1249-1258.
[12]Chen JC,Wu ML,Huang KC,Lin WW.HMG-CoAreductase inhibitors activate the unfolded Protein resPonse and induce cytoProtective GRP78 exPression.Cardiovasc Res.2008;80:138-150.
[13]Divald A,Kivity S,Wang P,Hochhauser E,Roberts B,Teichberg S,Gomes AV,Powell SR.Myocardial ischemic Preconditioning Preserves Postischemic function of the 26S Proteasome through diminished oxidative damage to 19S regulatory Particle subunits.Circ Res.2010;106:1829-1838.
[14]Terai K,Hiramoto Y,Masaki M,Sugiyama S,Kuroda T,Hori M,Kawase I,Hirota H.AMP-activated Protein kinase Protects cardiomyocytes against hyPoxic injury through attenuation of endoPlasmic reticulum stress.Mol Cell Biol.2005;25:9554-9575.
[15]ComPr Physiol.Author manuscriPt;available in PMC2017 Oct 19.Published in final edited form as:ComPr Physiol.2016 Dec 6,7(1):113-170.
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