蛋白激酶B通路、乙酰肝素酶、NADPH氧化酶在心肌缺血再灌注损伤中的作用及相互关系的研究进展

doi:10.3969/j.issn.1004-583X.2022.05.014

摘要/Abstract

摘要：

磷脂酰肌醇-3-激酶/蛋白激酶B(phosphatidylinositol-3-kinase/protein kinase B,PI3K/Akt)信号通路影响多种细胞因子,在心血管系统中起重要作用。近年来,蛋白激酶B(protein kinase B,Akt)、乙酰肝素酶(heparanase,HPSE)及NADPH氧化酶(NADPH oxidase,Nox)在缺血再灌注损伤中的作用引发越来越多的关注。已有研究表明,HPSE、Akt、Nox均参与了心肌细胞缺血再灌注损伤过程,并且相互作用。HPSE调控PI3K/Akt通路,而PI3K/Akt通路导致Nox产生增加,Nox又可以通过改变Akt信号传导激活Akt通路。本文通过综述HPSE、Akt、Nox在心肌缺血再灌注损伤中的作用及相互关系,旨在为临床心肌缺血再灌注的诊治提供理论依据。

关键词: 心肌再灌注损伤, 乙酰肝素酶, PI3K/Akt通路, Nox, 细胞凋亡

中图分类号:

R542.2

尹惠阳, 蔺雪峰, 韩轩茂. 蛋白激酶B通路、乙酰肝素酶、NADPH氧化酶在心肌缺血再灌注损伤中的作用及相互关系的研究进展[J]. 临床荟萃, 2022, 37(5): 459-462.

导出引用管理器 EndNote|Ris|BibTeX

链接本文: https://huicui.hebmu.edu.cn/CN/10.3969/j.issn.1004-583X.2022.05.014

https://huicui.hebmu.edu.cn/CN/Y2022/V37/I5/459

参考文献 44

[1]	Ramachandra CJA, Hernandez-Resendiz S, Crespo-Avilan GE, et al. Mitochondria in acute myocardial infarction and cardioprotection[J]. EBioMedicine, 2020, 57: 102884. doi: 10.1016/j.ebiom.2020.102884 URL
[2]	Liberale L, Gaul DS, Akhmedov A, et al. Endothelial SIRT6 blunts stroke size and neurological deficit by preserving blood-brain barrier integrity: A translational study[J]. Eur Heart J, 2020, 41(16): 1575-1587. doi: 10.1093/eurheartj/ehz712 pmid: 31603194
[3]	Sieve I, Münster-Kühnel AK, Hilfiker-Kleiner D. Regulation and function of endothelial glycocalyx layer in vascular diseases[J]. Vascul Pharmacol, 2018, 100: 26-33. doi: 10.1016/j.vph.2017.09.002 URL
[4]	Meng L, Zhang Y, Li D, et al. TIMP3 attenuates cerebral ischemia/reperfusioninduced apoptosis and oxidative stress in neurocytes by regulating the AKT pathway[J]. Exp Ther Med, 2021, 22(3): 973. doi: 10.3892/etm.2021.10405 URL
[5]	Cadenas S. ROS and redox signaling in myocardial ischemia-reperfusion injury and cardioprotection[J]. Free Radic Biol Med, 2018, 117: 76-89. doi: 10.1016/j.freeradbiomed.2018.01.024 URL
[6]	Manning BD, Toker A. AKT/PKB signaling: Navigating the network[J]. Cell, 2017, 169(3): 381-405. doi: 10.1016/j.cell.2017.04.001 URL
[7]	Fruman DA, Chiu H, Hopkins BD, et al. The PI3K pathway in human disease[J]. Cell, 2017, 170(4): 605-635. doi: S0092-8674(17)30865-6 pmid: 28802037
[8]	Sugiyama MG, Fairn GD, Antonescu CN. Akt-ing up just about everywhere: Compartment-specific Akt activation and function in receptor tyrosine kinase signaling[J]. Front Cell Dev Biol, 2019, 7: 70. doi: 10.3389/fcell.2019.00070 pmid: 31131274
[9]	Wetzel MD, Wenke JC. Mechanisms by which hydrogen sulfide attenuates muscle function following ischemia-reperfusion injury: Effects on Akt signaling, mitochondrial function, and apoptosis[J]. J Transl Med, 2019, 17(1): 33. doi: 10.1186/s12967-018-1753-7 URL
[10]	Jin XF, Wang S, Shen M, et al. Effects of rehabilitation training on apoptosis of nerve cells and the recovery of neural and motor functions in rats with ischemic stroke through the PI3K/Akt and Nrf2/ARE signaling pathways[J]. Brain Res Bull, 2017, 134: 236-245. doi: 10.1016/j.brainresbull.2017.08.011 URL
[11]	Sulaiman D, Li J, Devarajan A, et al. Paraoxonase 2 protects against acute myocardial ischemia-reperfusion injury by modulating mitochondrial function and oxidative stress via the PI3K/Akt/GSK-3β RISK pathway[J]. J Mol Cell Cardiol, 2019, 129: 154-164. doi: S0022-2828(19)30038-0 pmid: 30802459
[12]	Ye G, Fu Q, Jiang L, et al. Vascular smooth muscle cells activate PI3K/Akt pathway to attenuate myocardial ischemia/reperfusion-induced apoptosis and autophagy by secreting bFGF[J]. Biomed Pharmacother, 2018, 107: 1779-1785. doi: 10.1016/j.biopha.2018.05.113 URL
[13]	Sostre-Colón J, Uehara K, Whitlock AEG, et al. Hepatic AKT orchestrates adipose tissue thermogenesis via FGF21-dependent and-independent mechanisms[J]. Cell Rep, 2021, 35(7): 109128. doi: 10.1016/j.celrep.2021.109128 URL
[14]	Heusch G. Molecular basis of cardioprotection: Signal transduction in ischemic pre-, post-, and remote conditioning[J]. Circ Res, 2015, 116(4): 674-699. doi: 10.1161/CIRCRESAHA.116.305348 pmid: 25677517
[15]	Bassino E, Fornero S, Gallo MP, et al. Catestatin exerts direct protective effects on rat cardiomyocytes undergoing ischemia/reperfusion by stimulating PI3K-Akt-GSK3β pathway and preserving mitochondrial membrane potential[J]. PLoS One, 2015, 10(3): e0119790. doi: 10.1371/journal.pone.0119790 URL
[16]	Bubb KJ, Birgisdottir AB, Tang O, et al. Redox modification of caveolar proteins in the cardiovascular system-role in cellular signalling and disease[J]. Free Radic Biol Med, 2017, 109: 61-74. doi: 10.1016/j.freeradbiomed.2017.02.012 URL
[17]	Ghoti H, Ackerman S, Rivella S, et al. Heparanase level and procoagulant activity are increased in thalassemia and attenuated by janus kinase 2 inhibition[J]. Am J Pathol, 2020, 190(10): 2146-2154. doi: 10.1016/j.ajpath.2020.07.011 URL
[18]	Masola V, Bellin G, Gambaro G, et al. Heparanase: A multitasking protein involved in extracellular matrix (ECM) remodeling and intracellular events[J]. Cells, 2018, 7(12): 236. doi: 10.3390/cells7120236 URL
[19]	Masola V, Zaza G, Gambaro G, et al. Heparanase: A potential new factor involved in the renal epithelial mesenchymal transition (EMT) induced by ischemia/reperfusion (I/R) injury[J]. PLoS One, 2016, 11(7): e0160074. doi: 10.1371/journal.pone.0160074 URL
[20]	Masola V, Zaza G, Bellin G, et al. Heparanase regulates the M1 polarization of renal macrophages and their crosstalk with renal epithelial tubular cells after ischemia/reperfusion injury[J]. FASEB J, 2018, 32(2): 742-756. doi: 10.1096/fj.201700597R URL
[21]	Zhang Y, Murugesan P, Huang K, et al. NADPH oxidases and oxidase crosstalk in cardiovascular diseases: Novel therapeutic targets[J]. Nat Rev Cardiol, 2020, 17(3): 170-194. doi: 10.1038/s41569-019-0260-8 URL
[22]	Konior A, Schramm A, Czesnikiewicz-Guzik M, et al. NADPH oxidases in vascular pathology[J]. Antioxid Redox Signal, 2014, 20(17): 2794-814. doi: 10.1089/ars.2013.5607 URL
[23]	Manea SA, Constantin A, Manda G, et al. Regulation of Nox enzymes expression in vascular pathophysiology: Focusing on transcription factors and epigenetic mechanisms[J]. Redox Biol, 2015, 5: 358-366. doi: 10.1016/j.redox.2015.06.012 URL
[24]	Krylatov AV, Maslov LN, Voronkov NS, et al. Reactive oxygen species as intracellular signaling molecules in the cardiovascular system[J]. Curr Cardiol Rev, 2018, 14(4): 290-300. doi: 10.2174/1573403X14666180702152436 pmid: 29962348
[25]	Münzel T, Camici GG, Maack C, et al. Impact of oxidative stress on the heart and vasculature: Part 2 of a 3-part series[J]. J Am Coll Cardiol, 2017, 70(2): 212-229. doi: 10.1016/j.jacc.2017.05.035 URL
[26]	Milkovic L, Cipak GA, Cindric M, et al. Short overview of ROS as cell function regulators and their implications in therapy concepts[J]. Cells, 2019, 8(8): 793. doi: 10.3390/cells8080793 URL
[27]	Kietzmann T, Petry A, Shvetsova A, et al. The epigenetic landscape related to reactive oxygen species formation in the cardiovascular system[J]. Br J Pharmacol, 2017, 174(12): 1533-1554. doi: 10.1111/bph.13792 URL
[28]	Förstermann U, Xia N, Li H. Roles of vascular oxidative stress and nitric oxide in the pathogenesis of atherosclerosis[J]. Circ Res, 2017, 120(4): 713-735. doi: 10.1161/CIRCRESAHA.116.309326 pmid: 28209797
[29]	Matsushima S, Tsutsui H, Sadoshima J. Physiological and pathological functions of NADPH oxidases during myocardial ischemia-reperfusion[J]. Trends Cardiovasc Med, 2014, 24(5): 202-205. doi: 10.1016/j.tcm.2014.03.003 URL
[30]	Liu HQ, Li J, Liu XL, et al. Folic acid and RAAS blockers in ischemia/reperfusion-induced hepatic injury: A current mechanistic concept for understanding the incidence, significance & outcome[J]. Chem Biol Interact, 2020, 327: 109187. doi: 10.1016/j.cbi.2020.109187 URL
[31]	Ben-Zaken O, Gingis-Velitski S, Vlodavsky I, et al. Heparanase induces Akt phosphorylation via a lipid raft receptor[J]. Biochem Biophys Res Commun, 2007, 361(4): 829-834. doi: 10.1016/j.bbrc.2007.06.188 URL
[32]	Koganti R, Suryawanshi R, Shukla D. Heparanase, cell signaling, and viral infections[J]. Cell Mol Life Sci, 2020, 77(24): 5059-5077. doi: 10.1007/s00018-020-03559-y URL
[33]	Riaz A, Ilan N, Vlodavsky I, et al. Characterization of heparanase-induced phosphatidylinositol 3-kinase-AKT activation and its integrin dependence[J]. J Biol Chem, 2013, 288(17): 12366-12375. doi: 10.1074/jbc.M112.435172 URL
[34]	Nakanishi A, Wada Y, Kitagishi Y, et al. Link between PI3K/AKT/PTEN pathway and NOX protein in diseases[J]. Aging Dis, 2014, 5(3): 203-211. doi: 10.14336/AD.2014.0500203
[35]	Cai L, Stevenson J, Geng X, et al. Combining normobaric oxygen with ethanol or hypothermia prevents brain damage from thromboembolic stroke via PKC-Akt-NOX modulation[J]. Mol Neurobiol, 2017, 54(2): 1263-1277. doi: 10.1007/s12035-016-9695-7 URL
[36]	Koundouros N, Poulogiannis G. Phosphoinositide 3-kinase/Akt signaling and redox metabolism in cancer[J]. Front Oncol, 2018, 8: 160. doi: 10.3389/fonc.2018.00160 pmid: 29868481
[37]	Xia D, Halder B, Godoy C, et al. NADPH oxidase 1 mediates caerulein-induced pancreatic fibrosis in chronic pancreatitis[J]. Free Radic Biol Med, 2020, 147: 139-149. doi: 10.1016/j.freeradbiomed.2019.11.034 URL
[38]	Sack MN, Fyhrquist FY, Saijonmaa OJ, et al. Basic biology of oxidative stress and the cardiovascular system: Part 1 of a 3-part series[J]. J Am Coll Cardiol, 2017, 70(2): 196-211. doi: 10.1016/j.jacc.2017.05.034 URL
[39]	McGee MA, Abdel-Rahman AA. Enhanced vascular PI3K/Akt-NOX signaling underlies the peripheral NMDAR-mediated pressor response in conscious rats[J]. J Cardiovasc Pharmacol, 2014, 63(5): 395-405. doi: 10.1097/FJC.0000000000000059 URL
[40]	Moccetti F, Brown E, Xie A, et al. Myocardial infarction produces sustained proinflammatory endothelial activation in remote arteries[J]. J Am Coll Cardiol, 2018, 72(9): 1015-1026. doi: 10.1016/j.jacc.2018.06.044 URL
[41]	Mortezaee K, Goradel NH, Amini P, et al. NADPH oxidase as a target for modulation of radiation response; implications to carcinogenesis and radiotherapy[J]. Curr Mol Pharmacol, 2019, 12(1): 50-60. doi: 10.2174/1874467211666181010154709 pmid: 30318012
[42]	Shimura T, Sasatani M, Kamiya K, et al. Mitochondrial reactive oxygen species perturb AKT/cyclin D1 cell cycle signaling via oxidative inactivation of PP2A in low dose irradiated human fibroblasts[J]. Oncotarget, 2016, 7(3): 3559-70. doi: 10.18632/oncotarget.6518 URL
[43]	Schnelle M, Sawyer I, Anilkumar N, et al. NADPH oxidase-4 promotes eccentric cardiac hypertrophy in response to volume overload[J]. Cardiovasc Res, 2021, 117(1): 178-187. doi: 10.1093/cvr/cvz331 pmid: 31821410
[44]	Zhao QD, Viswanadhapalli S, Williams P, et al. NADPH oxidase 4 induces cardiac fibrosis and hypertrophy through activating Akt/mTOR and NFκB signaling pathways[J]. Circulation, 2015, 131(7): 643-655. doi: 10.1161/CIRCULATIONAHA.114.011079

蛋白激酶B通路、乙酰肝素酶、NADPH氧化酶在心肌缺血再灌注损伤中的作用及相互关系的研究进展

RichHTML

PDF (PC)

可视化

摘要/Abstract

引用本文

使用本文

参考文献 44

相关文章 15

编辑推荐

Metrics

本文评价

[1]	吕丽丽, 翟满满, 丁小艳, 陈永清. 线粒体转录因子A介导的线粒体功能障碍在糖尿病心肌病中的作用[J]. 临床荟萃, 2023, 38(5): 465-468.
[2]	叶蒙蒙, 李旎, 徐国栋, 邵国丰. miR-361在心血管疾病的研究进展[J]. 临床荟萃, 2021, 36(9): 843-849.
[3]	郭文选,朱瀛谦,沈方臻,王晓妮,潘飞,陈晶. Wnt信号通路抑制剂XAV939对人小细胞肺癌H446增殖及凋亡的影响[J]. 临床荟萃, 2016, 31(5): 543-546.
[4]	宋玉竹, 李英. 氢气对肾脏疾病的治疗作用及其研究进展[J]. 临床荟萃, 2016, 31(4): 443-446.
[5]	钱正瑶, 李广平, 李娇, 梁雪, 徐昭, 陈艳, 赵辉. 氧化型低密度脂蛋白诱导内皮细胞凋亡中前蛋白转化酶枯草溶菌素9与炎症因子的关系[J]. 临床荟萃, 2016, 31(4): 396-402.
[6]	曹丽叶;张爱民;程树杰;靖立良;张全. 重症急性胰腺炎并发肺损伤大鼠的生存素基因表达及对血红素加氧酶1及细胞凋亡的影响[J]. 临床荟萃, 2014, 29(9): 1019-1021.
[7]	李汭傧;崔炜;耿雪. 经皮冠状动脉介入治疗前应用他汀类药物患者围手术期心肌损伤的meta分析[J]. 临床荟萃, 2014, 29(2): 125-133.
[8]	何珂;胡蕴;郭慕红;毛晓明. 促甲状腺激素受体抗体对人肝癌细胞HepG2凋亡和增殖的影响[J]. 临床荟萃, 2014, 29(1): 45-48.
[9]	马晓峰;高琴;边惠萍;刘品发. 瑞舒伐他汀对经皮冠状动脉介入治疗患者术后炎症反应与心肌损伤的影响[J]. 临床荟萃, 2013, 28(9): 1042-1044.
[10]	陈琳;喻明. 咖啡因对棕榈酸作用下β细胞增殖和凋亡影响[J]. 临床荟萃, 2013, 28(7): 772-774782.
[11]	冉广宇;杨彦彪. 盐酸小檗碱对人乳腺癌MCF-7细胞增殖及凋亡的影响[J]. 临床荟萃, 2013, 28(6): 683-685.
[12]	孙玉;栾森;张洪海;邓尧;郑加生;陈德喜. P53凋亡刺激蛋白2在gp120诱导的神经细胞凋亡中的作用[J]. 临床荟萃, 2013, 28(11): 1207-0.
[13]	马玉腾;郭宪立;高恒波;苏建玲;霍淑花;胡军利;姚冬奇;王荣英;陈慧;刘建辉;田英平;石汉文. 百草枯中毒致大鼠肺组织损伤时氨溴索对肺组织Bcl-2/Bax的表达及细胞凋亡的影响[J]. 临床荟萃, 2012, 27(9): 767-0.
[14]	叶应琴;李惠新. 红景天甙抗肿瘤作用的研究进展[J]. 临床荟萃, 2012, 27(7): 642-644.
[15]	杜静华;张艳;任伟光;孔令波;赵素贤;南月敏. 斑蝥酸钠维生素B6联合经皮肝动脉化疗栓塞对原发性肝癌患者血清sFasL/sFas的影响[J]. 临床荟萃, 2012, 27(3): 213-216.