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1.辽宁中医药大学,沈阳 110847
2.辽宁中医药大学 附属医院,沈阳 110000
3.沈阳药科大学,沈阳 110016
Received:30 March 2024,
Published Online:25 June 2024,
Published:20 December 2024
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袁子阳,张艳,张伟等.基于PINK1/Parkin通路探讨线粒体自噬防治心力衰竭作用及中医药治疗进展[J].中国实验方剂学杂志,2024,30(24):262-271.
YUAN Ziyang,ZHANG Yan,ZHANG Wei,et al.Role of Mitophagy in Prevention and Treatment of Heart Failure Based on PINK1/Parkin Pathway and Treatment with Traditional Chinese Medicine: A Review[J].Chinese Journal of Experimental Traditional Medical Formulae,2024,30(24):262-271.
袁子阳,张艳,张伟等.基于PINK1/Parkin通路探讨线粒体自噬防治心力衰竭作用及中医药治疗进展[J].中国实验方剂学杂志,2024,30(24):262-271. DOI: 10.13422/j.cnki.syfjx.20241998.
YUAN Ziyang,ZHANG Yan,ZHANG Wei,et al.Role of Mitophagy in Prevention and Treatment of Heart Failure Based on PINK1/Parkin Pathway and Treatment with Traditional Chinese Medicine: A Review[J].Chinese Journal of Experimental Traditional Medical Formulae,2024,30(24):262-271. DOI: 10.13422/j.cnki.syfjx.20241998.
心力衰竭是一组复杂的临床综合征,为心血管疾病发展的终末阶段,死亡率极高,但由于病理机制复杂,目前还未寻找到一种十分有效的治疗方法。线粒体是细胞最为关键的细胞器之一,不仅在细胞内起着能量供应的重要作用,还广泛参与细胞的各项生命活动,如氧化应激的调节、细胞凋亡的调控等,线粒体功能的正常与否对维持机体正常生命活动具有重要意义。近年来,研究发现,线粒体的异常功能与多种疾病的发生和发展相关,其中与心力衰竭发病之间关系密切,线粒体稳态失衡是心肌细胞死亡,心力衰竭发病的关键因素,而线粒体自噬作为一种调控机体线粒体稳态的方式对防治心力衰竭具有重要意义。中医药疗法是我国独有治疗方式,现已广泛应用于临床当中,而其在治疗心力衰竭中疗效显著,具有独特优势。目前现代药理学研究表明,中药单体及复方能靶向调节心肌细胞线粒体稳态,影响线粒体自噬,保护心肌细胞,然机制尚不清楚。因此,该文从PTEN诱导假定激酶1(PINK1)/E3泛素蛋白连接酶(Parkin)通路出发探讨PINK1/Parkin通路在线粒体自噬及心力衰竭中的作用机制,并对PINK1/Parkin通路介导的线粒体自噬对心力衰竭的影响进行综述,同时结合中医药探讨其对PINK1/Parkin介导线粒体自噬对心力衰竭的治疗作用,旨在从PINK1/Parkin调控线粒体自噬角度为中医药防治心力衰竭提供新的思路与方法。
Heart failure is a group of complex clinical syndromes that represent the final stage of cardiovascular disease development, characterized by an extremely high mortality rate. However, due to the complexity of the pathological mechanisms, an effective treatment method has not yet been found. Mitochondria are among the most critical organelles in cells, playing an essential role in energy supply and widely participating in various life activities, such as the regulation of oxidative stress and apoptosis. The normal functioning of mitochondria is crucial for maintaining the body's normal life activities. In recent years, studies have found that mitochondrial dysfunction is associated with the occurrence and progression of various diseases, particularly closely related to the onset of heart failure. An imbalance in mitochondrial homeostasis is a key factor in cardiomyocyte death and the onset of heart failure. Mitochondrial autophagy, as a means of regulating mitochondrial homeostasis, is significant for the prevention and treatment of heart failure. Traditional Chinese medicine (TCM) therapy is a unique treatment approach in China now widely applied in clinical practice, demonstrating significant efficacy in treating heart failure, with unique advantages. Modern pharmacological research indicates that Chinese medicine monomers and compounds can target and regulate mitochondrial homeostasis in cardiomyocytes, affect mitochondrial autophagy, and protect cardiomyocytes, though the specific mechanisms remain unclear. Therefore, this paper explored the mechanisms of the PTEN-induced putative kinase 1 (PINK1)/Parkin pathway in mitochondrial autophagy and heart failure, reviewed the effects of PINK1/Parkin-mediated mitochondrial autophagy on heart failure, and discussed the therapeutic effects of PINK1/Parkin-mediated mitochondrial autophagy on heart failure in conjunction with TCM. This paper is expected to provide new ideas and methods for the prevention and treatment of heart failure from the perspective of PINK1/Parkin regulation of mitochondrial autophagy.
SAVARESE G , BECHER P M , LUND L H , et al . Global burden of heart failure:A comprehensive and updated review of epidemiology [J]. Cardiovasc Res , 2023 , 118 ( 17 ): 3272 - 3287 .
BOZKURT B , COATS A J , TSUTSUI H , et al . Universal definition and classification of heart failure:A report of the Heart Failure Society of America,Heart Failure Association of the European Society of Cardiology,Japanese Heart Failure Society and Writing Committee of the Universal Definition of Heart Failure [J]. J Card Fail , 2021 , doi: 10.1016/j.cardfail.2021.01.022 http://dx.doi.org/10.1016/j.cardfail.2021.01.022 .
BOZKURT B , COATS A , TSUTSUI H , et al . Universal definition and classification of heart failure:A report of the Heart Failure Society of America,Heart Failure Association of the European Society of Cardiology,Japanese Heart Failure Society and Writing Committee of the Universal Definition of Heart Failure:Endorsed by the Canadian Heart Failure Society,Heart Failure Association of India,Cardiac Society of Australia and New Zealand,and Chinese Heart Failure Association [J]. Eur J Heart Fail , 2021 , 23 ( 3 ): 352 - 380 .
VÁSQUEZ-TRINCADO C , GARCÍA-CARVAJAL I , PENNANEN C , et al . Mitochondrial dynamics,mitophagy and cardiovascular disease [J]. J Physiol , 2016 , 594 ( 3 ): 509 - 525 .
ASHRAFI G , SCHWARZ T L . The pathways of mitophagy for quality control and clearance of mitochondria [J]. Cell Death Differ , 2013 , 20 ( 1 ): 31 - 42 .
DEAS E , PLUN-FAVREAU H , GANDHI S , et al . PINK1 cleavage at position A103 by the mitochondrial protease PARL [J]. Hum Mol Genet , 2011 , 20 ( 5 ): 867 - 879 .
PICCA A , FAITG J , AUWERX J , et al . Mitophagy in human health,ageing and disease [J]. Nat Metab , 2023 , 5 ( 12 ): 2047 - 2061 .
NUNNARI J , SUOMALAINEN A . Mitochondria:In sickness and in health [J]. Cell , 2012 , 148 ( 6 ): 1145 - 1159 .
TAHRIR F G , LANGFORD D , AMINI S , et al . Mitochondrial quality control in cardiac cells:Mechanisms and role in cardiac cell injury and disease [J]. J Cell Physiol , 2019 , 234 ( 6 ): 8122 - 8133 .
XU Y , SHEN J , RAN Z . Emerging views of mitophagy in immunity and autoimmune diseases [J]. Autophagy , 2020 , 16 ( 1 ): 3 - 17 .
AJOOLABADY A , WANG S , KROEMER G , et al . Targeting autophagy in ischemic stroke:From molecular mechanisms to clinical therapeutics [J]. Pharmacol Ther , 2021 , 225 : 107848 .
AJOOLABADY A , AGHANEJAD A , BI Y , et al . Enzyme-based autophagy in anti-neoplastic management:From molecular mechanisms to clinical therapeutics [J]. Biochim Biophys Acta Rev Cancer , 2020 , 1874 ( 1 ): 188366 .
PICKRELL A M , YOULE R J . The roles of PINK1,parkin,and mitochondrial fidelity in Parkinson's disease [J]. Neuron , 2015 , 85 ( 2 ): 257 - 273 .
GREENE A W , GRENIER K , AGUILETA M A , et al . Mitochondrial processing peptidase regulates PINK1 processing,import and Parkin recruitment [J]. EMBO Rep , 2012 , 13 ( 4 ): 378 - 385 .
HASSON S A , KANE L A , YAMANO K , et al . High-content genome-wide RNAi screens identify regulators of parkin upstream of mitophagy [J]. Nature , 2013 , 504 ( 7479 ): 291 - 295 .
JIN S M , YOULE R J . The accumulation of misfolded proteins in the mitochondrial matrix is sensed by PINK1 to induce PARK2/Parkin-mediated mitophagy of polarized mitochondria [J]. Autophagy , 2013 , 9 ( 11 ): 1750 - 1757 .
WENZEL D M , LISSOUNOV A , BRZOVIC P S , et al . UBCH7 reactivity profile reveals parkin and HHARI to be RING/HECT hybrids [J]. Nature , 2011 , 474 ( 7349 ): 105 - 108 .
MATSUDA N , SATO S , SHIBA K , et al . PINK1 stabilized by mitochondrial depolarization recruits Parkin to damaged mitochondria and activates latent Parkin for mitophagy [J]. J Cell Biol , 2010 , 189 ( 2 ): 211 - 221 .
GAN Z Y , CALLEGARI S , COBBOLD S A , et al . Activation mechanism of PINK1 [J]. Nature , 2022 , 602 ( 7896 ): 328 - 335 .
SCHMID E T , PYO J H , WALKER D W . Neuronal induction of BNIP3-mediated mitophagy slows systemic aging in Drosophila [J]. Nat Aging , 2022 , 2 ( 6 ): 494 - 507 .
KANE L A , LAZAROU M , FOGEL A I , et al . PINK1 phosphorylates ubiquitin to activate Parkin E3 ubiquitin ligase activity [J]. J Cell Biol , 2014 , 205 ( 2 ): 143 - 153 .
MCEWAN D G , POPOVIC D , GUBAS A , et al . PLEKHM1 regulates autophagosome-lysosome fusion through HOPS complex and LC3/GABARAP proteins [J]. Mol Cell , 2015 , 57 ( 1 ): 39 - 54 .
HEO J M , ORDUREAU A , PAULO J A , et al . The PINK1-Parkin mitochondrial ubiquitylation pathway drives a program of OPTN/NDP52 recruitment and TBK1 activation to promote mitophagy [J]. Mol Cell , 2015 , 60 ( 1 ): 7 - 20 .
RICHTER B , SLITER D A , HERHAUS L , et al . Phosphorylation of OPTN by TBK1 enhances its binding to Ub chains and promotes selective autophagy of damaged mitochondria [J]. Proc Natl Acad Sci USA , 2016 , 113 ( 15 ): 4039 - 4044 .
HEO J M , ORDUREAU A , SWARUP S , et al . RAB7A phosphorylation by TBK1 promotes mitophagy via the PINK-PARKIN pathway [J]. Sci Adv , 2018 , 4 ( 11 ): eaav0443 .
VARGAS J , WANG C , BUNKER E , et al . Spatiotemporal control of ULK1 activation by NDP52 and TBK1 during selective autophagy [J]. Mol Cell , 2019 , 74 ( 2 ): 347 - 362 .
MUKHERJEE R , CHAKRABARTI O . Ubiquitin-mediated regulation of the E3 ligase GP78 by MGRN1 in trans affects mitochondrial homeostasis [J]. J Cell Sci , 2016 , 129 ( 4 ): 757 - 773 .
CALLE X , GARRIDO-MORENO V , LOPEZ-GALLARDO E , et al . Mitochondrial E3 ubiquitin ligase 1 (MUL1) as a novel therapeutic target for diseases associated with mitochondrial dysfunction [J]. IUBMB Life , 2022 , 74 ( 9 ): 850 - 865 .
TANAKA A , CLELAND M M , XU S , et al . Proteasome and p97 mediate mitophagy and degradation of mitofusins induced by Parkin [J]. J Cell Biol , 2010 , 191 ( 7 ): 1367 - 1380 .
FU M , ST-PIERRE P , SHANKAR J , et al . Regulation of mitophagy by the Gp78 E3 ubiquitin ligase [J]. Mol Biol Cell , 2013 , 24 ( 8 ): 1153 - 1162 .
WANG B , NIE J , WU L , et al . AMPK α 2 protects against the development of heart failure by enhancing mitophagy via PINK1 phosphorylation [J]. Circ Res , 2018 , 122 ( 5 ): 712 - 729 .
ZHU P , WAN K , YIN M , et al . RIPK3 Induces cardiomyocyte necroptosis via inhibition of AMPK-Parkin-mitophagy in cardiac remodelling after myocardial infarction [J]. Oxid Med Cell Longev , 2021 , 2021 : 6635955 .
SONG M , CHEN Y , GONG G , et al . Super-suppression of mitochondrial reactive oxygen species signaling impairs compensatory autophagy in primary mitophagic cardiomyopathy [J]. Circ Res , 2014 , 115 ( 3 ): 348 - 353 .
ZHU Q , COMBS M E , LIU J , et al . GRAF1 integrates PINK1-Parkin signaling and actin dynamics to mediate cardiac mitochondrial homeostasis [J]. Nat Commun , 2023 , 14 ( 1 ): 8187 .
YANG X , JIANG T , WANG Y , et al . The role and mechanism of SIRT1 in resveratrol-regulated osteoblast autophagy in osteoporosis rats [J]. Sci Rep , 2019 , 9 ( 1 ): 18424 .
ABUDUREYIMU M , ZHAO L , LUO X , et al . Influences of ALDH2 on cardiomyocyte apoptosis in heart failure rats through regulating PINK1-Parkin signaling pathway-mediated mitophagy [J]. Cell Mol Biol (Noisy-le-grand) , 2022 , 68 ( 2 ): 94 - 102 .
DADSON K , HAUCK L , HAO Z , et al . The E3 ligase Mule protects the heart against oxidative stress and mitochondrial dysfunction through Myc-dependent inactivation of Pgc-1 α and Pink1 [J]. Sci Rep , 2017 , 7 : 41490 .
GUO Y , JIN S , YUAN H , et al . DNA-unresponsive platinum(Ⅱ) complex induces ERS-mediated mitophagy in cancer cells [J]. J Med Chem , 2022 , 65 ( 1 ): 520 - 530 .
KIM J H , YI Y S , KIM M Y , et al . Role of ginsenosi des,the main active components of Panax ginseng ,in inflammatory responses and diseases [J]. J Ginseng Res , 2017 , 41 ( 4 ): 435 - 443 .
GUAN S , XIN Y , DING Y , et al . Ginsenoside Rg 1 protects against cardiac remodeling in heart failure via SIRT1/PINK1/Parkin-mediated mitophagy [J]. Chem Biodivers , 2023 , 20 ( 2 ): e202200730 .
SONG D , HAO J , FAN D . Biological properties and clinical applications of berberine [J]. Front Med , 2020 , 14 ( 5 ): 564 - 582 .
ABUDUREYIMU M , YU W , CAO R Y , et al . Berberine promotes cardiac function by upregulating PINK1/Parkin-mediated mitophagy in heart failure [J]. Front Physiol , 2020 , 11 : 565751 .
ZHANG J , LAN N . Hirudin variants production by genetic engineered microbial factory [J]. Biotechnol Genet Eng Rev , 2018 , 34 ( 2 ): 261 - 280 .
LUO G , CHEN L , CHEN M , et al . Hirudin inhibit the formation of NLRP3 inflammasome in cardiomyocytes via suppressing oxidative stress and activating mitophagy [J]. Heliyon , 2024 , 10 ( 1 ): e23077 .
李旭阳 , 张东伟 , 赵宏月 . 黄芪甲苷对缺血再灌注诱导的大鼠心肌细胞及线粒体自噬的调节作用机制研究 [J]. 中医药学报 , 2020 , 48 ( 9 ): 27 - 32 .
XIAO Z , LIU W , MU Y P , et al . Pharmacological effects of salvianolic Acid B against oxidative damage [J]. Front Pharmacol , 2020 , 11 : 572373 .
LI Q , ZUO Z , PAN Y , et al . Salvianolic acid B alleviates myocardial ischemia injury by suppressing NLRP3 inflammasome activation via SIRT1-AMPK-PGC-1 α signaling pathway [J]. Cardiovasc Toxicol , 2022 , 22 ( 9 ): 842 - 857 .
蒋婷婷 , 刘雅蓉 , 施晓艳 , 等 . 丹皮酚减轻SIRT6/PARP1介导的DNA损伤抑制血管平滑肌细胞衰老的作用 [J]. 中国实验方剂学杂志 , 2023 , 29 ( 10 ): 83 - 92 .
刘超 , 王明娟 , 范彦芳 , 等 . 丹皮酚对大鼠心肌梗死后心脏功能的改善及其对Pink1/Parkin的影响 [J]. 世界科学技术—中医药现代化 , 2020 , 22 ( 5 ): 1428 - 1436 .
REN X , CHEN L , XIE J , et al . Resveratrol ameliorates mitochondrial elongation via Drp1/Parkin/PINK1 signaling in senescent-like cardiomyocytes [J]. Oxid Med Cell Longev , 2017 , 2017 : 4175353 .
LUO C , ZHANG Y , GUO H , et al . Ferulic Acid attenuates hypoxia/reoxygenation injury by suppressing mitophagy through the PINK1/Parkin signaling pathway in H9c2 Cells [J]. Front Pharmacol , 2020 , 11 : 103 .
ZHANG J , FAN F , LIU A , et al . Icariin:A potential molecule for treatment of knee osteoarthritis [J]. Front Pharmacol , 2022 , 13 : 811808 .
程相阁 , 刘万周 , 王东伟 . 淫羊藿苷对心力衰竭大鼠线粒体自噬及能量代谢的影响 [J]. 西北药学杂志 , 2022 , 37 ( 4 ): 51 - 57 .
别明珂 , 曾昭文 , 陈新宇 . 真武汤对慢性心力衰竭大鼠心肌细胞ERK5及线粒体自噬关键蛋白的影响 [J]. 湖南中医药大学学报 , 2021 , 41 ( 12 ): 1840 - 1845 .
曹程浩 , 韩丽华 , 张会超 . 基于AMP K介导的线粒体自噬分析温阳益气方 改善大鼠梗死后心衰的药理机制 [J]. 中国比较医学杂志 , 2019 , 29 ( 12 ): 39 - 44 .
李想 , 张华敏 , 崔海峰 , 等 . 栝楼薤白半夏汤对心肌缺血再灌注损伤大鼠自噬及PINK1/Parkin通路作用研究 [J]. 中国中医基础医学杂志 , 2020 , 26 ( 11 ): 1626 - 1630 .
庞延 , 卢健棋 , 唐梅玲 , 等 . 强心汤对慢性心力衰竭模型大鼠梗死心肌区组织活性氧及PINK1/parkin介导的线粒体自噬的影响 [J]. 中医杂志 , 2023 , 64 ( 7 ): 722 - 728 .
GUAN Z , CHEN J , WANG L , et al . Nuanxinkang prevents the development of myocardial infarction-induced chronic heart failure by promoting PINK1/Parkin-mediated mitophagy [J]. Phytomedicine , 2023 , 108 : 154494 .
QIU Z , HU Y , GENG Y , et al . Xin Fu Kang oral liquid inhibits excessive myocardial mitophagy in a rat model of advanced heart failure [J]. Am J Transl Res , 2018 , 10 ( 10 ): 3198 - 3210 .
严士海 , 方慧华 , 田磊 , 等 . 基于AMPK-mt TFA-PINK1信号探讨参葵通脉颗粒改善慢性心衰心肌线粒体损伤的机制 [J]. 中药新药与临床药理 , 2018 , 29 ( 6 ): 738 - 743 .
陈广 , 吴晓霞 , 蔡虎志 , 等 . 温阳振衰颗粒对慢性心衰大鼠模型心肌细胞线粒体自噬关键蛋白的影响 [J]. 时珍国医国药 , 2019 , 30 ( 1 ): 16 - 18 .
YU J , LI Y , LIU X , et al . Mitochondrial dynamics modulation as a critical contribution for Shenmai injection in attenuating hypoxia/reoxygenation injury [J]. J Ethnopharmacol , 2019 , 237 : 9 - 19 .
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