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摘要: 心肌细胞的微管对维持心肌细胞的正常结构、功能有着密切的关系。而微管的稳定性主要是受微管相关蛋白(MAPs)调节，包括MAP2、MAP4及tau等。翻译后修饰(PTMs)对MAP蛋白的表达和功能的正常发挥有着重要作用。在心力衰竭(心衰)情况下，通常会发生不同程度异常的PTMs，通过调控这些异常的修饰作用可以对心衰进行干预和治疗。因此，本文从心肌细胞微管的功能、微管蛋白的调控等方面出发，对近年来国内外的心衰与微管调控相关研究进行总结，以期为心衰治疗提供理论参考。Abstract: Microtubules in cardiomyocytes have been found to be closely related to the maintenance of normal structure and function of cardiomyocytes. The stability of microtubules is mainly regulated by microtubule-associated proteins(MAPs), including MAP2, MAP4 and tau. Post-translational modifications(PTMs) play an important role in the normal expression and function of MAP proteins. In heart failure, varying degrees of abnormal PTMs usually occur, and it has been shown that intervention and treatment of heart failure can be achieved by modulating these abnormal modifications. Therefore, in this article, we summarize the studies on heart failure and microtubule regulation in recent years from the perspective of the function of microtubules in cardiomyocytes and the regulation of microtubule proteins at home and abroad, in order to provide some theoretical references for the treatment of heart failure.
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Key words:
- heart failure /
- microtubules /
- tubulin /
- post-translational modifications
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[1] McDonagh TA, Metra M, Adamo M, et al. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure[J]. Eur Heart J, 2021, 42(36): 3599-3726. doi: 10.1093/eurheartj/ehab368
[2] 程敏, 廖玉华, 袁璟. 2022 ESC速递: 心力衰竭相关临床研究解读[J]. 临床心血管病杂志, 2022, 38(10): 774-776. https://www.cnki.com.cn/Article/CJFDTOTAL-LCXB202210003.htm
[3] Truby LK, Rogers JG. Advanced Heart Failure: Epidemiology, Diagnosis, and Therapeutic Approaches[J]. JACC Heart Fail, 2020, 8(7): 523-536. doi: 10.1016/j.jchf.2020.01.014
[4] Tomasoni D, Adamo M, Lombardi CM, et al. Highlights in heart failure[J]. ESC Heart Fail, 2019, 6(6): 1105-1127. doi: 10.1002/ehf2.12555
[5] Meilhac SM, Buckingham ME. The deployment of cell lineages that form the mammalian heart[J]. Nat Rev Cardiol, 2018, 15(11): 705-724. doi: 10.1038/s41569-018-0086-9
[6] Litviňuková M, Talavera-López C, Maatz H, et al. Cells of the adult human heart[J]. Nature, 2020, 588(7838): 466-472. doi: 10.1038/s41586-020-2797-4
[7] Lopaschuk GD, Karwi QG, Tian R, et al. Cardiac Energy Metabolism in Heart Failure[J]. Circ Res, 2021, 128(10): 1487-1513. doi: 10.1161/CIRCRESAHA.121.318241
[8] Whelan RS, Kaplinskiy V, Kitsis RN. Cell death in the pathogenesis of heart disease: mechanisms and significance[J]. Annu Rev Physiol, 2010, 72: 19-44. doi: 10.1146/annurev.physiol.010908.163111
[9] 柯樊, 廖梦阳, 邱志华, 等. β肾上腺素能受体在梗死后心脏重构中作用的研究进展[J]. 临床心血管病杂志, 2021, 37(4): 298-303. doi: 10.13201/j.issn.1001-1439.2021.04.003
[10] Steele DF, Fedida D. Cytoskeletal roles in cardiac ion channel expression[J]. Biochimica Et Biophysica Acta, 2014, 1838(2): 665-673. doi: 10.1016/j.bbamem.2013.05.001
[11] Dehmelt L, Halpain S. The MAP2/Tau family of microtubule-associated proteins[J]. Genome Biol, 2005, 6(1): 204.
[12] Magiera MM, Singh P, Gadadhar S, et al. Tubulin Posttranslational Modifications and Emerging Links to Human Disease[J]. Cell, 2018, 173(6): 1323-1327. doi: 10.1016/j.cell.2018.05.018
[13] Caporizzo MA, Chen CY, Prosser BL. Cardiac microtubules in health and heart disease[J]. Exp Biol Med(Maywood), 2019, 244(15): 1255-1272. doi: 10.1177/1535370219868960
[14] Goldstein MA, Entman ML. Microtubules in mammalian heart muscle[J]. J Cell Biol, 1979, 80(1): 183-195. doi: 10.1083/jcb.80.1.183
[15] Caporizzo MA, Prosser BL. The microtubule cytoskeleton in cardiac mechanics and heart failure[J]. Nat Rev Cardiol, 2022, 19(6): 364-378. doi: 10.1038/s41569-022-00692-y
[16] Steele DF, Eldstrom J, Fedida D. Mechanisms of cardiac potassium channel trafficking[J]. J Physiol, 2007, 582(Pt 1): 17-26.
[17] Goodson HV, Jonasson EM. Microtubules and Microtubule-Associated Proteins[J]. Cold Spring Harb Perspect Biol, 2018, 10(6): a022608. doi: 10.1101/cshperspect.a022608
[18] Chen CY, Caporizzo MA, Bedi K, et al. Suppression of detyrosinated microtubules improves cardiomyocyte function in human heart failure[J]. Nat Med, 2018, 24(8): 1225-1233. doi: 10.1038/s41591-018-0046-2
[19] Zile MR, Green GR, Schuyler GT, et al. Cardiocyte cytoskeleton in patients with left ventricular pressure overload hypertrophy[J]. J Am Coll Cardiol, 2001, 37(4): 1080-1084. doi: 10.1016/S0735-1097(00)01207-9
[20] Witjas-Paalberends ER, Güçlü A, Germans T, et al. Gene-specific increase in the energetic cost of contraction in hypertrophic cardiomyopathy caused by thick filament mutations[J]. Cardiovasc Res, 2014, 103(2): 248-257. doi: 10.1093/cvr/cvu127
[21] Bollen IAE, van der Meulen M, de Goede K, et al. Cardiomyocyte Hypocontractility and Reduced Myofibril Density in End-Stage Pediatric Cardiomyopathy[J]. Front Physiol, 2017, 8: 1103. doi: 10.3389/fphys.2017.01103
[22] Scholz D, Baicu CF, Tuxworth WJ, et al. Microtubule-dependent distribution of mRNA in adult cardiocytes[J]. Am J Physiol Heart Circ Physiol, 2008, 294(3): H1135-H1144. doi: 10.1152/ajpheart.01275.2007
[23] Robison P, Caporizzo MA, Ahmadzadeh H, et al. Detyrosinated microtubules buckle and bear load in contracting cardiomyocytes[J]. Science, 2016, 352(6284): aaf0659. doi: 10.1126/science.aaf0659
[24] Chinnakkannu P, Samanna V, Cheng G, et al. Site-specific microtubule-associated protein 4 dephosphorylation causes microtubule network densification in pressure overload cardiac hypertrophy[J]. J Biol Chem, 2010, 285(28): 21837-21848. doi: 10.1074/jbc.M110.120709
[25] Cheng G, Takahashi M, Shunmugavel A, et al. Basis for MAP4 dephosphorylation-related microtubule network densification in pressure overload cardiac hypertrophy[J]. J Biol Chem, 2010, 285(49): 38125-38140. doi: 10.1074/jbc.M110.148650
[26] Illenberger S, Drewes G, Trinczek B, et al. Phosphorylation of microtubule-associated proteins MAP2 and MAP4 by the protein kinase p110mark. Phosphorylation sites and regulation of microtubule dynamics[J]. J Biol Chem, 1996, 271(18): 10834-10843. doi: 10.1074/jbc.271.18.10834
[27] Trinczek B, Brajenovic M, Ebneth A, et al. MARK4 is a novel microtubule-associated proteins/microtubule affinity-regulating kinase that binds to the cellular microtubule network and to centrosomes[J]. J Biol Chem, 2004, 279(7): 5915-5923. doi: 10.1074/jbc.M304528200
[28] Drewes G, Ebneth A, Mandelkow EM. MAPs, MARKs and microtubule dynamics[J]. Trends Biochem Sci, 1998, 23(8): 307-311. doi: 10.1016/S0968-0004(98)01245-6
[29] Yu X, Chen X, Amrute-Nayak M, et al. MARK4 controls ischaemic heart failure through microtubule detyrosination[J]. Nature, 2021, 594(7864): 560-565. doi: 10.1038/s41586-021-03573-5
[30] L'Hernault SW, Rosenbaum JL. Chlamydomonas alpha-tubulin is posttranslationally modified by acetylation on the epsilon-amino group of a lysine[J]. Biochemistry, 1985, 24(2): 473-478. doi: 10.1021/bi00323a034
[31] Maruta H, Greer K, Rosenbaum JL. The acetylation of alpha-tubulin and its relationship to the assembly and disassembly of microtubules[J]. J Cell Biol, 1986, 103(2): 571-579. doi: 10.1083/jcb.103.2.571
[32] Xu Z, Schaedel L, Portran D, et al. Microtubules acquire resistance from mechanical breakage through intralumenal acetylation[J]. Science, 2017, 356(6335): 328-332. doi: 10.1126/science.aai8764
[33] Choudhary C, Kumar C, Gnad F, et al. Lysine acetylation targets protein complexes and co-regulates major cellular functions[J]. Science, 2009, 325(5942): 834-840. doi: 10.1126/science.1175371
[34] Chu CW, Hou F, Zhang J, et al. A novel acetylation of β-tubulin by San modulates microtubule polymerization via down-regulating tubulin incorporation[J]. Mol Biol Cell, 2011, 22(4): 448-456. doi: 10.1091/mbc.e10-03-0203
[35] Akella JS, Wloga D, Kim J, et al. MEC-17 is an alpha-tubulin acetyltransferase[J]. Nature, 2010, 467(7312): 218-222. doi: 10.1038/nature09324
[36] Shida T, Cueva JG, Xu Z, et al. The major alpha-tubulin K40 acetyltransferase alphaTAT1 promotes rapid ciliogenesis and efficient mechanosensation[J]. Proc Natl Acad Sci U S A, 2010, 107(50): 21517-21522. doi: 10.1073/pnas.1013728107
[37] Palazzo A, Ackerman B, Gundersen GG. Cell biology: Tubulin acetylation and cell motility[J]. Nature, 2003, 421(6920): 230.
[38] North BJ, Marshall BL, Borra MT, et al. The human Sir2 ortholog, SIRT2, is an NAD+－dependent tubulin deacetylase[J]. Mol Cell, 2003, 11(2): 437-444. doi: 10.1016/S1097-2765(03)00038-8
[39] McLendon PM, Ferguson BS, Osinska H, et al. Tubulin hyperacetylation is adaptive in cardiac proteotoxicity by promoting autophagy[J]. Proc Natl Acad Sci U S A, 2014, 111(48): E5178-E5186.
[40] Tao H, Yang J-J, Shi K-H, et al. Epigenetic factors MeCP2 and HDAC6 control α-tubulin acetylation in cardiac fibroblast proliferation and fibrosis[J]. Inflamm Res, 2016, 65(5): 415-426. doi: 10.1007/s00011-016-0925-2
[41] Villalobos E, Criollo A, Schiattarella GG, et al. Fibroblast Primary Cilia Are Required for Cardiac Fibrosis[J]. Circulation, 2019, 139(20): 2342-2357. doi: 10.1161/CIRCULATIONAHA.117.028752
[42] Eddé B, Rossier J, Le Caer JP, et al. Posttranslational glutamylation of alpha-tubulin[J]. Science, 1990, 247(4938): 83-85. doi: 10.1126/science.1967194
[43] Valenstein ML, Roll-Mecak A. Graded Control of Microtubule Severing by Tubulin Glutamylation[J]. Cell, 2016, 164(5): 911-921. doi: 10.1016/j.cell.2016.01.019
[44] Kerr JP, Robison P, Shi G, et al. Detyrosinated microtubules modulate mechanotransduction in heart and skeletal muscle[J]. Nature Communications, 2015, 6: 8526. doi: 10.1038/ncomms9526
[45] Ki SM, Kim JH, Won SY, et al. CEP41-mediated ciliary tubulin glutamylation drives angiogenesis through AURKA-dependent deciliation[J]. EMBO Rep, 2020, 21(2): e48290.
[46] Fan Z, Peng W, Wang Z, et al. Identification of biomarkers associated with metabolic cardiovascular disease using mRNA-SNP-miRNA regulatory network analysis[J]. BMC Cardiovasc Disord, 2021, 21(1): 351. doi: 10.1186/s12872-021-02166-4
[47] Saji K, Fukumoto Y, Suzuki J, et al. Colchicine, a microtubule depolymerizing agent, inhibits myocardial apoptosis in rats[J]. Tohoku J Exp Med, 2007, 213(2): 139-148. doi: 10.1620/tjem.213.139
[48] Caporizzo MA, Chen CY, Bedi K, et al. Microtubules Increase Diastolic Stiffness in Failing Human Cardiomyocytes and Myocardium[J]. Circulation, 2020, 141(11): 902-915. doi: 10.1161/CIRCULATIONAHA.119.043930
[49] Caporizzo MA, Chen CY, Salomon AK, et al. Microtubules Provide a Viscoelastic Resistance to Myocyte Motion[J]. Biophys J, 2018, 115(9): 1796-1807. doi: 10.1016/j.bpj.2018.09.019
[50] Fassett JT, Xu X, Hu X, et al. Adenosine regulation of microtubule dynamics in cardiac hypertrophy[J]. Am J Physiol Heart Circ Physiol, 2009, 297(2): H523-H532. doi: 10.1152/ajpheart.00462.2009
[51] Fassett J, Xu X, Kwak D, et al. Adenosine kinase attenuates cardiomyocyte microtubule stabilization and protects against pressure overload-induced hypertrophy and LV dysfunction[J]. J Mol Cell Cardiol, 2019, 130: 49-58. doi: 10.1016/j.yjmcc.2019.03.015
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