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浙江大学学报(医学版)  2016, Vol. 45 Issue (3): 308-314    DOI: 10.3785/j.issn.1008-9292.2019.05.15
综述     
锌与自噬
刘巧云1, 沈汉明2, 夏大静1
1. 浙江大学公共卫生学院毒理系, 浙江 杭州 310058;
2. 新加坡国立大学杨潞龄医学院生理系, 117597
Zinc and autophagy
LIU Qiaoyun1, SHEN Hanming2, XIA Dajing1
1. Department of Toxicology, School of Public Health, Zhejiang University, Hangzhou 310058, China;
2. Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, 117597, Singapore
全文: PDF(979 KB)  
摘要: 

细胞自噬主要指对胞质内受损的细胞器或生物大分子进行降解和回收利用的过程。自噬过程依赖于溶酶体,并由一系列复杂的信号分子进行调控。锌元素通过锌转运蛋白和锌指蛋白等多种酶或蛋白发挥催化和结构作用,在自噬的发生发展过程中发挥了重要作用。自噬调节紊乱同样也会导致胞内锌离子代谢稳态的重大改变。许多研究结果还提示锌对细胞的保护作用很可能是通过自噬来实现的。本文总结了当前国内外自噬研究进展,重点介绍锌在细胞自噬过程中发挥的作用和细胞自噬在锌代谢中的作用以及自噬介导的锌对细胞的保护作用等,揭示锌与自噬之间相互调控的发生机制,阐明自噬与疾病之间的关系,以期为治疗和预防多种人类重大疾病提供相关思路。

关键词 自噬肿瘤综述    
Abstract

Autophagy refers to a catabolic process,in which the damaged organelles or biological macromolecules, such as protein aggregates, are degraded via lysosome. The completion of autophagy depends on a series of autophagy-related genes (Atgs) and many upstream regulatory molecules. Zinc is an essential trace element, and plays an important role in the process of autophagy as a component of enzymes and structural proteins like zinc transporters or zinc finger protein. The regulation of autophagy is closely associated with the zinc ion homeostasis. In addition, many studies suggest that the protective effects of zinc on cells are likely to be done by autophagy. This review aims to summarize the current research progress and discuss the reciprocal regulation mechanism between zinc and autophagy, which may provide insights into the intricate roles of autophagy in diseases and find novel strategies for treatment and prevention of human diseases.

Key wordsZinc    Autophagy    Neoplasms    Review
收稿日期: 2015-10-19
CLC:  R225  
基金资助:

国家自然科学基金(31471297)

通讯作者: 夏大静(1968-),女,博士,教授,主要从事免疫毒理学研究;E-mail:dxia@zju.edu.cn;http://orcid.org/0000-0003-1645-9046     E-mail: dxia@zju.edu.cn
作者简介: 刘巧云(1992-),女,硕士研究生,主要从事农药毒理学研究;E-mail:liuqiaoyun@zju.edu.cn;http://orcid.org/0000-0003-3100-9502
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引用本文:

刘巧云 等. 锌与自噬[J]. 浙江大学学报(医学版), 2016, 45(3): 308-314.
LIU Qiaoyun, SHEN Hanming, XIA Dajing. Zinc and autophagy. Journal of ZheJiang University(Medical Science), 2016, 45(3): 308-314.

链接本文:

http://www.zjujournals.com/xueshu/med/CN/10.3785/j.issn.1008-9292.2019.05.15      或      http://www.zjujournals.com/xueshu/med/CN/Y2016/V45/I3/308

[1] MIZUSHIMA N, LEVINE B, CUERVO A M, et al. Autophagy fights disease through cellular self-digestion[J]. Nature, 2008, 451(7182):1069-1075.
[2] MIZUSHIMA N, LEVINE B. Autophagy in mammalian development and differentiation[J]. Nat Cell Biol, 2010, 12(9): 823-830.
[3] HIRANO T, MURAKAMI M, FUKADA T, et al. Roles of zinc and zinc signaling in immunity: zinc as an intracellular signaling molecule[J]. Adv Immunol, 2008, 97: 149-176.
[4] LIUZZI J P, GUO L, YOO C, et al. Zinc and autophagy[J]. Biometals, 2014, 27(6): 1087-1096.
[5] ZHAO Z, FUX B, GOODWIN M, et al. Autophagosome-independent essential function for the autophagy protein Atg5 in cellular immunity to intracellular pathogens[J]. Cell Host Microbe, 2008, 4(5): 458-469.
[6] YANG Z, KLIONSKY D J. Eaten alive: a history of macroautophagy[J]. Nat Cell Biol, 2010, 12(9): 814-822.
[7] JUNG C H, RO S H, CAO J, et al. mTOR regulation of autophagy[J]. FEBS Lett, 2010, 584(7):1287-1295.
[8] REGGIORI F,SHINTANI T,NAIR U, et al. Atg9 cycles between mitochondria and the pre-autophagosomal structure in yeasts[J]. Autophagy, 2005, 1(2):101-109.
[9] ITAKURA E, MIZUSHIMA N. Characterization of autophagosome formation site by a hierarchical analysis of mammalian Atg proteins[J]. Autophagy, 2010, 6(6): 764-776.
[10] JUNG C H, JUN C B, RO S H, et al. ULK-Atg13-FIP200 complexes mediate mTOR signaling to the autophagy machinery[J]. Mol Biol Cell, 2009, 20(7): 1992-2003.
[11] MIZUSHIMA N, KUMA A, KOBAYASHI Y, et al. Mouse Apg16L, a novel WD-repeat protein, targets to the autophagic isolation membrane with the Apg12-Apg5 conjugate[J]. J Cell Sci, 2003, 116(Pt 9): 1679-1688.
[12] YU X, LONG Y C, SHEN H M. Differential regulatory functions of three classes of phosphatidylinositol and phosphoinositide 3-kinases in autophagy[J]. Autophagy, 2015, 11(10):1711-1728.
[13] HE R, PENG J, YUAN P, et al. Divergent roles of BECN1 in LC3 lipidation and autophagosomal function[J]. Autophagy, 2015, 11(5): 740-747.
[14] IN S, HONG C W, CHOI B, et al. Inhibition of mitochondrial clearance and Cu/Zn-SOD activity enhance 6-hydroxydopamine-induced neuronal apoptosis[J]. Mol Neurobiol, 2016, 53(1):777-791.
[15] PAN R, TIMMINS G S, LIU W, et al. Autophagy mediates astrocyte death during zinc-potentiated ischimia-reperfusion injury[J]. Biol Trace Elem Res, 2015, 166(1): 89-95.
[16] LIUZZI J P, YOO C. Role of zinc in the regulation of autophagy during ethanol exposure in human hepatoma cells[J]. Biol Trace Elem Res, 2013, 156(1-3): 350-356.
[17] HWANG J J, KIM H N, KIM J, et al. Zinc(Ⅱ) ion mediates tamoxifen-induced autophagy and cell death in MCF-7 breast cancer cell line[J]. Biometals, 2010, 23(6): 997-1013.
[18] ALAM S, KELLEHER S L. Cellular mechanisms of zinc dysregulation: a perspective on zinc homeostasis as an etiological factor in the development and progression of breast cancer[J]. Nutrients, 2012, 4(8): 875-903.
[19] LI Y, ZHANG L, LI K, et al. ZNF32 inhibits autophagy through the mTOR pathway and protects MCF-7 cells from stimulus-induced cell death[J]. Sci Rep, 2015, 5: 9288.
[20] HUNG H H, HUANG W P, PAN C Y. Dopamine-and zinc-induced autophagosome formation facilitates PC12 cell survival[J]. Cell Biol Toxicol, 2013, 29(6): 415-429.
[21] SEO B R, LEE S J, CHO K S, et al. The zinc ionophore clioquinol reverses autophagy arrest in chloroquine-treated ARPE-19 cells and in APP/mutant presenilin-1-transfected Chinese hamster ovary cells[J]. Neurobiol Aging, 2015, 36(12):3228-3238.
[22] KIM J, KUNDU M, VIOLLET B, et al. AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1[J]. Nat Cell Biol, 2011,13(2): 132-141.
[23] LEE S J, KOH J Y. Roles of zinc and metallothionein-3 in oxidative stress-induced lysosomal dysfunction, cell death, and autophagy in neurons and astrocytes[J]. Mol Brain, 2010,3(1): 30.
[24] LICHTLEN P, SCHAFFNER W. The "metal transcription factor" MTF-1: biological facts and medical implications[J]. Swiss Med Wkly, 2002, 131(45-46): 647-652.
[25] CARTHARIUS K, FRECH K, GROTE K, et al. MatInspector and beyond: promoter analysis based on transcription factor binding sites[J]. Bioinformatics, 2005, 21(13): 2933-2942.
[26] KIM J H, JEON J, SHIN M, et al. Regulation of the catabolic cascade in osteoarthritis by the zinc-ZIP8-MTF1 axis[J]. Cell, 2014, 156(4): 730-743.
[27] RYU M S, LANGKAMP-HENKEN B, CHANG S M, et al. Genomic analysis, cytokine expression, and microRNA profiling reveal biomarkers of human dietary zinc depletion and homeostasis[J]. Proc Natl Acad Sci U S A, 2011, 108(52): 20970-20975.
[28] ENG B H, GUERIONT M L, EIDE D, et al. Sequence analyses and phylogenetic characterization of the ZIP family of metal ion transport proteins[J]. J Membr Biol, 1998, 166(1): 1-7.
[29] PATRUSHEV N, SEIDEL-ROGOL B, SALAZAR G. Angiotensin Ⅱ requires zinc and downregulation of the zinc transporters ZnT3 and ZnT10 to induce senescence of vascular smooth muscle cells[J/OL]. PLoS One, 2012, 7(3):e33211.
[30] BOSOMWORTH H J, ADLARD P A, FORD D, et al. Altered expression of ZnT10 in Alzheimer's disease brain[J/OL]. PLoS One, 2013, 8(5):e65475.
[31] KAMBE T. An overview of a wide range of functions of ZnT and Zip zinc transporters in the secretory pathway[J]. Biosci Biotechnol Biochem, 2011, 75(6): 1036-1043.
[32] KUMA A, MIZUSHIMA N, ISHIHARA N, et al. Formation of the approximately 350-kDa Apg12-Apg5.Apg16 multimeric complex, mediated by Apg16 oligomerization, is essential for autophagy in yeast[J]. J Biol Chem, 2002, 277(21): 18619-18625.
[33] DING W X, LI M, CHEN X, et al. Autophagy reduces acute ethanol-induced hepatotoxicity and steatosis in mice[J]. Gastroenterology, 2010, 139(5): 1740-1752.
[34] DERETIC V, SAITOH T, AKIRA S. Autophagy in infection, inflammation and immunity[J]. Nat Rev Immunol, 2013, 13(10): 722-737.
[35] MANLEY S, WILLIAMS J A, DING W X. Role of p62/SQSTM1 in liver physiology and pathogenesis[J]. Exp Biol Med (Maywood), 2013, 238(5): 525-538.
[36] Wellcome Trust Case Control Consortium. Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls[J]. Nature, 2007, 447(7145): 661-678.
[37] TAYLOR K M, VICHOVA P, JORDAN N, et al. ZIP7-mediated intracellular zinc transport contributes to aberrant growth factor signaling in antihormone-resistant breast cancer cells[J]. Endocrinology, 2008, 149(10): 4912-4920.
[38] SUMMERSGILL H, ENGLAND H, LOPEZ-CASTEJON G, et al. Zinc depletion regulates the processing and secretion of IL-1β[J/OL]. Cell Death Dis, 2014, 5(1):e1040.
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