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Medical Diagnosis 2024
LC3B在心力衰竭中的研究进展
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Abstract:
心力衰竭是各种心血管疾病的终末阶段，亦是医学界尚未攻克的最后堡垒，给患者、家庭、社会带来沉重负担。LC3B属于LC3/GABARAP蛋白家族，通过介导自噬底物的招募、自噬体的运动、自噬基因的转录，参与自噬调节，保护细胞应对饥饿、缺血、缺氧，抗线粒体氧化应激，在心肌梗死、心肌病、心肌肥大中有重要作用。本综述对LC3B的生物学特点、功能及其通过调节自噬改善心力衰竭进行综述，并为心力衰竭的治疗提供新思路。
Heart failure is the final stage of all kinds of cardiovascular diseases, and it is also the last bastion that has not yet been conquered by the medical profession, which has brought a heavy burden to the patients, their families and the society. LC3B belongs to the LC3/GABARAP family of proteins and is involved in the regulation of autophagy by mediating the recruitment of autophagic substrates, autophagosome motility, and transcription of autophagy genes, which protects the cells against starvation, ischemia, and hypoxia, and is resistant to mitochondrial oxidative stress, and has an important role in myocardial infarction, cardiomyopathy, and myocardial hypertrophy. This review provides an overview of the biological characteristics and functions of LC3B and its ability to ameliorate heart failure by regulating autophagy, and provides new ideas for the treatment of heart failure.
| [1] | Johansen, T. and Lamark, T. (2020) Selective Autophagy: ATG8 Family Proteins, LIR Motifs and Cargo Receptors. Journal of Molecular Biology, 432, 80-103. https://doi.org/10.1016/j.jmb.2019.07.016 |
| [2] | Nieto-Torres, J.L., Shanahan, S., Chassefeyre, R., Chaiamarit, T., Zaretski, S., Landeras-Bueno, S., et al. (2021) LC3B Phosphorylation Regulates FYCO1 Binding and Directional Transport of Autophagosomes. Current Biology, 31, 3440-3449.E7. https://doi.org/10.1016/j.cub.2021.05.052 |
| [3] | Kournoutis, A. and Johansen, T. (2023) LC3B Is a Cofactor for Lmx1b-Mediated Transcription of Autophagy Genes in Dopaminergic Neurons. Journal of Cell Biology, 222, e202303008. https://doi.org/10.1083/jcb.202303008 |
| [4] | Tang, Y., Kay, A., Jiang, Z. and Arkin, M.R. (2022) LC3B Binds to the Autophagy Protease Atg4b with High Affinity Using a Bipartite Interface. Biochemistry, 61, 2295-2302. https://doi.org/10.1021/acs.biochem.2c00482 |
| [5] | Wesch, N., Kirkin, V. and Rogov, V.V. (2020) Atg8-Family Proteins—Structural Features and Molecular Interactions in Autophagy and Beyond. Cells, 9, Article 2008. https://doi.org/10.3390/cells9092008 |
| [6] | Wang, X. and Cui, T. (2017) Autophagy Modulation: A Potential Therapeutic Approach in Cardiac Hypertrophy. American Journal of Physiology-Heart and Circulatory Physiology, 313, H304-H319. https://doi.org/10.1152/ajpheart.00145.2017 |
| [7] | Hwang, H.J., Ha, H., Lee, B.S., Kim, B.H., Song, H.K. and Kim, Y.K. (2022) LC3B Is an RNA-Binding Protein to Trigger Rapid mRNA Degradation during Autophagy. Nature Communications, 13, Article No. 1436. https://doi.org/10.1038/s41467-022-29139-1 |
| [8] | Huang, R., Xu, Y., Wan, W., Shou, X., Qian, J., You, Z., et al. (2015) Deacetylation of Nuclear LC3 Drives Autophagy Initiation under Starvation. Molecular Cell, 57, 456-466. https://doi.org/10.1016/j.molcel.2014.12.013 |
| [9] | Song, T., Su, H., Yin, W., Wang, L. and Huang, R. (2019) Acetylation Modulates LC3 Stability and Cargo Recognition. FEBS Letters, 593, 414-422. https://doi.org/10.1002/1873-3468.13327 |
| [10] | Nieto-Torres, J.L., Zaretski, S., Liu, T., Adams, P.D. and Hansen, M. (2023) Post-Translational Modifications of ATG8 Proteins—An Emerging Mechanism of Autophagy Control. Journal of Cell Science, 136, jcs259725. https://doi.org/10.1242/jcs.259725 |
| [11] | Liu, H., Liu, P., Shi, X., Yin, D. and Zhao, J. (2018) NR4A2 Protects Cardiomyocytes against Myocardial Infarction Injury by Promoting Autophagy. Cell Death Discovery, 4, Article No. 27. https://doi.org/10.1038/s41420-017-0011-8 |
| [12] | Zhang, X., Wang, Q., Wang, X., Chen, X., Shao, M., Zhang, Q., et al. (2019) Tanshinone IIA Protects against Heart Failure Post-Myocardial Infarction via AMPKs/mTOR-Dependent Autophagy Pathway. Biomedicine & Pharmacotherapy, 112, Article ID: 108599. https://doi.org/10.1016/j.biopha.2019.108599 |
| [13] | Sciarretta, S., Yee, D., Nagarajan, N., Bianchi, F., Saito, T., Valenti, V., et al. (2018) Trehalose-Induced Activation of Autophagy Improves Cardiac Remodeling after Myocardial Infarction. Journal of the American College of Cardiology, 71, 1999-2010. https://doi.org/10.1016/j.jacc.2018.02.066 |
| [14] | Gao, F., Su, Q., Yang, W., Pang, S., Wang, S., Cui, Y., et al. (2018) Functional Variants in the LC3B Gene Promoter in Acute Myocardial Infarction. Journal of Cellular Biochemistry, 119, 7339-7349. https://doi.org/10.1002/jcb.27035 |
| [15] | Da‘as, S.I., Fakhro, K., Thanassoulas, A., Krishnamoorthy, N., Saleh, A., Calver, B.L., et al. (2018) Hypertrophic Cardiomyopathy-Linked Variants of Cardiac Myosin-Binding Protein C3 Display Altered Molecular Properties and Actin Interaction. Biochemical Journal, 475, 3933-3948. https://doi.org/10.1042/bcj20180685 |
| [16] | Singh, S.R., Zech, A.T.L., Geertz, B., Reischmann-Düsener, S., Osinska, H., Prondzynski, M., et al. (2017) Activation of Autophagy Ameliorates Cardiomyopathy in Mybpc3-Targeted Knockin Mice. Circulation: Heart Failure, 10, e004140. https://doi.org/10.1161/circheartfailure.117.004140 |
| [17] | Orphanou, N., Papatheodorou, E. and Anastasakis, A. (2021) Dilated Cardiomyopathy in the Era of Precision Medicine: Latest Concepts and Developments. Heart Failure Reviews, 27, 1173-1191. https://doi.org/10.1007/s10741-021-10139-0 |
| [18] | Zhou, J., Ng, B., Ko, N.S.J., Fiedler, L.R., Khin, E., Lim, A., et al. (2019) Titin Truncations Lead to Impaired Cardiomyocyte Autophagy and Mitochondrial Function in Vivo. Human Molecular Genetics, 28, 1971-1981. https://doi.org/10.1093/hmg/ddz033 |
| [19] | Kanamori, H., Naruse, G., Yoshida, A., Minatoguchi, S., Watanabe, T., Kawaguchi, T., et al. (2019) Metformin Enhances Autophagy and Provides Cardioprotection in δ-Sarcoglycan Deficiency-Induced Dilated Cardiomyopathy. Circulation: Heart Failure, 12, e005418. https://doi.org/10.1161/circheartfailure.118.005418 |
| [20] | Kanamori, H., Yoshida, A., Naruse, G., Endo, S., Minatoguchi, S., Watanabe, T., et al. (2022) Impact of Autophagy on Prognosis of Patients with Dilated Cardiomyopathy. Journal of the American College of Cardiology, 79, 789-801. https://doi.org/10.1016/j.jacc.2021.11.059 |
| [21] | Gong, H., Lyu, X., Dong, L., Tan, S., Li, S., Peng, J., et al. (2022) Obstructive Sleep Apnea Impacts Cardiac Function in Dilated Cardiomyopathy Patients through Circulating Exosomes. Frontiers in Cardiovascular Medicine, 9, Article 699764. https://doi.org/10.3389/fcvm.2022.699764 |
| [22] | Shi, S. and Jiang, P. (2022) Therapeutic Potentials of Modulating Autophagy in Pathological Cardiac Hypertrophy. Biomedicine & Pharmacotherapy, 156, Article ID: 113967. https://doi.org/10.1016/j.biopha.2022.113967 |
| [23] | Oldfield, C.J., Duhamel, T.A. and Dhalla, N.S. (2020) Mechanisms for the Transition from Physiological to Pathological Cardiac Hypertrophy. Canadian Journal of Physiology and Pharmacology, 98, 74-84. https://doi.org/10.1139/cjpp-2019-0566 |
| [24] | Oyabu, J., Yamaguchi, O., Hikoso, S., Takeda, T., Oka, T., Murakawa, T., et al. (2013) Autophagy-Mediated Degradation Is Necessary for Regression of Cardiac Hypertrophy during Ventricular Unloading. Biochemical and Biophysical Research Communications, 441, 787-792. https://doi.org/10.1016/j.bbrc.2013.10.135 |
| [25] | Kobara, M., Toba, H. and Nakata, T. (2022) Roles of Autophagy in Angiotensin II-Induced Cardiomyocyte Apoptosis. Clinical and Experimental Pharmacology and Physiology, 49, 1342-1351. https://doi.org/10.1111/1440-1681.13719 |
| [26] | Xie, Y., Lai, S., Lin, Q., Xie, X., Liao, J., Wang, H., et al. (2018) CDC20 Regulates Cardiac Hypertrophy via Targeting Lc3-Dependent Autophagy. Theranostics, 8, 5995-6007. https://doi.org/10.7150/thno.27706 |
| [27] | Zhang, Y., Ding, Y., Li, M., Yuan, J., Yu, Y., Bi, X., et al. (2022) Microrna-34c-5p Provokes Isoprenaline-Induced Cardiac Hypertrophy by Modulating Autophagy via Targeting Atg4b. Acta Pharmaceutica Sinica B, 12, 2374-2390. https://doi.org/10.1016/j.apsb.2021.09.020 |
| [28] | Jin, Y., Zhou, H., Fan, D., Che, Y., Wang, Z., Wang, S., et al. (2020) TMEM173 Protects against Pressure Overload‐Induced Cardiac Hypertrophy by Modulating Autophagy. Journal of Cellular Physiology, 236, 5176-5192. https://doi.org/10.1002/jcp.30223 |
| [29] | Ott, C., Jung, T., Brix, S., John, C., Betz, I.R., Foryst-Ludwig, A., et al. (2021) Hypertrophy-Reduced Autophagy Causes Cardiac Dysfunction by Directly Impacting Cardiomyocyte Contractility. Cells, 10, Article 805. https://doi.org/10.3390/cells10040805 |
| [30] | Liu, R., Zhang, H.B., Yang, J., et al. (2018) Curcumin Alleviates Isoproterenol-Induced Cardiac Hypertrophy and Fibrosis through Inhibition of Autophagy and Activation of mTOR. European Review for Medical and Pharmacological Sciences, 22, 7500-7508. |
| [31] | 杨伟, 苗立坤, 陈章荣. 自噬与心肌重构研究进展[J]. 心血管病学进展, 2022, 43(6): 535-537, 546. |
| [32] | Farhan, H., Kundu, M. and Ferro-Novick, S. (2017) The Link between Autophagy and Secretion: A Story of Multitasking Proteins. Molecular Biology of the Cell, 28, 1161-1164. https://doi.org/10.1091/mbc.e16-11-0762 |
| [33] | Wu, X., Liu, Z., Yu, X., Xu, S. and Luo, J. (2020) Autophagy and Cardiac Diseases: Therapeutic Potential of Natural Products. Medicinal Research Reviews, 41, 314-341. https://doi.org/10.1002/med.21733. |
| [34] | 张东霞, 刘凤岐, 张瑞英. 自噬与心力衰竭的治疗[J]. 心血管病学进展, 2017, 38(6): 696-699. |
