|
|
去乙酰化酶家族成员2的研究进展
|
Abstract:
SIRT2作为Sirtuins家族的一员，基因位于常染色体19q13.2上，与细胞质中的微管蛋白共定位，主要存在于胰腺、肝脏、肌肉、脑等代谢相关组织中；是经典的III型组蛋白去乙酰化酶。研究表明，SIRT2主要通过对靶基因的翻译后修饰调控代谢通路；调节多种细胞功能，如有丝分裂、细胞分化、应激反应、细胞存活、和稳态，因此在健康和疾病中发挥着重要作用。目前针对SIRT2在诸如二型糖尿病、神经系统疾病、心血管疾病、癌症等中的研究已有众多的报道，但其在多种疾病中都表现出了双重性作用，既有保护性的，亦有伤害性的，这为临床治疗提供靶点带来了相当大的难题。我们综述了近年来国内外的相关文献，拟对SIRT2相关的临床疾病及分子机制作进一步阐述，期望对未来相关临床提供参考。
As a member of the Sirtuins family, SIRT2 gene is located on auto-chromosome 19q13.2, colocalized with tubulin in cytoplasm, and mainly exists in metabolism re-lated tissues such as pancreas, liver, muscle and brain. It’s a classic type III histone deacetylase. Studies have shown that SIRT2 regulates metabolic pathways mainly through posttranslational modification of target genes. Regulates a variety of cellular functions, such as mitosis, cell differen-tiation, stress response, cell survival, and homeostasis, and thus plays an important role in health and disease. At present, there have been numerous reports on SIRT2’s role in such diseases as type 2 diabetes, nervous system diseases, cardiovascular diseases, cancer, etc. However, SIRT2 has shown dual effects in a variety of diseases, including both protective and harmful effects, which brings considerable difficulties in providing targets for clinical treatment. We reviewed relevant literatures at home and abroad in recent years, and planned to further elaborate the clinical dis-eases and molecular mechanisms related to SIRT2, hoping to provide reference for future clinical studies.
| [1] | [1] Song, J., Yang, B., Jia, X., et al. (2018) Distinctive Roles of Sirtuins on Diabetes, Protective or Detrimental? Frontiers in Endocrinology, 9, Article 724. https://doi.org/10.3389/fendo.2018.00724 |
| [2] | Hong, J.Y. and Lin, H. (2021) Sirtuin Modulators in Cellular and Animal Models of Human Diseases. Frontiers in Pharmacology, 12, Article 735044. https://doi.org/10.3389/fphar.2021.735044 |
| [3] | Ungurianu, A., Zanfirescu, A. and Margina, D. (2022) Regulation of Gene Expression through Food-Curcumin as a Sirtuin Activity Modulator. Plants, 11, Article No. 1741. https://doi.org/10.3390/plants11131741 |
| [4] | Colloca, A., Balestrieri, A., Anastasio, C., Balestrieri, M.L. and D’Onofrio, N. (2022) Mitochondrial Sirtuins in Chronic Degenerative Diseases: New Metabolic Targets in Colorectal Cancer. International Journal of Molecular Sciences, 23, Article No. 3212. https://doi.org/10.3390/ijms23063212 |
| [5] | Ezhilarasan, D., Lakshmi, T., Subha, M., et al. (2022) The Ambiguous Role of Sirtuins in Head and Neck Squamous Cell Carcinoma. Oral Diseases, 28, 559-567. https://doi.org/10.1111/odi.13798 |
| [6] | Pugliese, N., Plaz Torres, M.C., Petta, S., et al. (2022) Is There an ‘ideal’ Diet for Patients with NAFLD? European Journal of Clinical Investigation, 52, e13659. https://doi.org/10.1111/eci.13659 |
| [7] | Roshdy, E., Mustafa, M., Shaltout, A.E., et al. (2021) Selective SIRT2 In-hibitors as Promising Anticancer Therapeutics: An Update from 2016 to 2020. European Journal of Medicinal Chemis-try, 224, Article ID: 113709.
https://doi.org/10.1016/j.ejmech.2021.113709 |
| [8] | Elkhwanky, M.-S. and Hakkola, J. (2018) Extranuclear Sirtuins and Metabolic Stress. Antioxidants & Redox Signaling, 28, 662-676. https://doi.org/10.1089/ars.2017.7270 |
| [9] | Zheng, M., Hu, C., Wu, M. and Chin, Y.E. (2021) Emerging Role of SIRT2 in Non-Small Cell Lung Cancer. Oncology Letters, 22, Article No. 731. https://doi.org/10.3892/ol.2021.12992 |
| [10] | Taneja, A., Ravi, V., Hong, J.Y., Lin, H. and Sundaresan, N.R. (2021) Emerging Roles of Sirtuin 2 in Cardiovascular Diseases. The FASEB Journal, 35, e21841. https://doi.org/10.1096/fj.202100490R |
| [11] | Pouwels, S., Sakran, N., Graham, Y., et al. (2022) Non-Alcoholic Fatty Liver Disease (NAFLD): A Review of Pathophysiology, Clinical Management and Effects of Weight Loss. BMC Endocrine Disorders, 22, Article No. 63.
https://doi.org/10.1186/s12902-022-00980-1 |
| [12] | Scorletti, E. and Carr, R.M. (2022) A New Perspective on NAFLD: Focusing on Lipid Droplets. Journal of Hepatology, 76, 934-945. https://doi.org/10.1016/j.jhep.2021.11.009 |
| [13] | Shah, P.A., Patil, R. and Harrison, S.A. (2023) NAFLD-Related Hepatocellular Carcinoma: The Growing Challenge. Hepatology, 77, 323-338. https://doi.org/10.1002/hep.32542 |
| [14] | Chen, B., Tang, W.H.W., Rodriguez, M., et al. (2022) NAFLD in Cardio-vascular Diseases: A Contributor or Comorbidity? Seminars in Liver Disease, 42, 465-474. https://doi.org/10.1055/s-0042-1757712 |
| [15] | Li, W., Liu, J., Cai, J., et al. (2022) NAFLD as a Continuous Driver in the Whole Spectrum of Vascular Disease. Journal of Molecular and Cellular Cardiology, 163, 118-132. https://doi.org/10.1016/j.yjmcc.2021.10.007 |
| [16] | Wong, V.W.S., Zelber-Sagi, S., Cusi, K., et al. (2022) Manage-ment of NAFLD in Primary Care Settings. Liver International, 42, 2377-2389. https://doi.org/10.1111/liv.15404 |
| [17] | Yang, M. and Wei, L. (2022) Impact of NAFLD on the Outcome of Patients with Chronic Hepatitis B in Asia. Liver International, 42, 1981-1990. https://doi.org/10.1111/liv.15252 |
| [18] | Nakatsuka, T., Tateishi, R. and Koike, K. (2022) Changing Clinical Man-agement of NAFLD in Asia. Liver International, 42, 1955-1968. https://doi.org/10.1111/liv.15046 |
| [19] | Chauhan, M., Singh, K. and Thuluvath, P.J. (2022) Bariatric Surgery in NAFLD. Digestive Diseases and Sciences, 67, 408-422. https://doi.org/10.1007/s10620-021-07317-3 |
| [20] | Li, D.-J., Sun, S.-J., Fu, J.-T., et al. (2021) NAD+-Boosting Therapy Alleviates Nonalcoholic Fatty Liver Disease via Stimulating a Novel Exerkine Fndc5/Irisin. Theranostics, 11, 4381-4402. https://doi.org/10.7150/thno.53652 |
| [21] | Zhang, B., Xu, D., She, L., et al. (2018) Silybin Inhibits NLRP3 Inflammasome Assembly through the NAD+/SIRT2 Pathway in Mice with Nonalcoholic Fatty Liver Disease. The FASEB Journal, 32, 757-767.
https://doi.org/10.1096/fj.201700602R |
| [22] | Leal, H., Cardoso, J., Valerio, P., et al. (2022) SIRT2 Deficiency Ex-acerbates Hepatic Steatosis via a Putative Role of the ER Stress Pathway. International Journal of Molecular Sciences, 23, Article No. 6790.
https://doi.org/10.3390/ijms23126790 |
| [23] | Ren, H., Hu, F., Wang, D., et al. (2021) Sirtuin 2 Prevents Liver Stea-tosis and Metabolic Disorders by Deacetylation of Hepatocyte Nuclear Factor 4alpha. Hepatology, 74, 723-740. https://doi.org/10.1002/hep.31773 |
| [24] | Zhou, Z., Qi, J., Kim, J.-W., et al. (2020) AK-1, a Sirt2 Inhibitor, Alleviates Carbon Tetrachloride-Induced Hepatotoxicity in Vivo and in Vitro. Toxicology Mechanisms and Methods, 30, 324-335.
https://doi.org/10.1080/15376516.2020.1729915 |
| [25] | Wu, D.-Q., Ding, Q.-Y., Tao, N.-N., et al. (2022) SIRT2 Promotes HBV Transcription and Replication by Targeting Transcription Factor p53 to Increase the Activities of HBV Enhancers and Promoters. Frontiers in Microbiology, 13, Article 836446. https://doi.org/10.3389/fmicb.2022.836446 |
| [26] | Cheng, S.-T., Ren, J.-H., Cai, X.-F., Jiang, H. and Chen, J. (2018) HBx-Elevated SIRT2 Promotes HBV Replication and Hepatocarcinogenesis. Biochemical and Biophysical Research Communications, 496, 904-910.
https://doi.org/10.1016/j.bbrc.2018.01.127 |
| [27] | Wang, B., Ye, Y., Yang, X., et al. (2020) SIRT2-Dependent IDH1 Deacetylation Inhibits Colorectal Cancer and Liver Metastases. EMBO Reports, 21, e48183. https://doi.org/10.15252/embr.201948183 |
| [28] | Zhang, Y., Long, X., Ruan, X., et al. (2021) SIRT2-Mediated Deacetylation and Deubiquitination of C/EBPβ Prevents Ethanol-Induced Liver Injury. Cell Discovery, 7, Article No. 93. https://doi.org/10.1038/s41421-021-00326-6 |
| [29] | Shao, Y., Wang, X., Zhou, Y., et al. (2021) Pterostilbene Atten-uates RIPK3-Dependent Hepatocyte Necroptosis in Alcoholic Liver Disease via SIRT2-Mediated NFATc4 Deacetyla-tion. Toxicology, 461, Article ID: 152923.
https://doi.org/10.1016/j.tox.2021.152923 |
| [30] | Chen, G., Huang, P. and Hu, C. (2020) The Role of SIRT2 in Can-cer: A Novel Therapeutic Target. International Journal of Cancer, 147, 3297-3304. https://doi.org/10.1002/ijc.33118 |
| [31] | Chen, X., Lu, W. and Wu, D. (2021) Sirtuin 2 (SIRT2): Confusing Roles in the Pathophysiology of Neurological Disorders. Frontiers in Neuroscience, 15, Article 614107. https://doi.org/10.3389/fnins.2021.614107 |
| [32] | Manjula, R., Anuja, K. and Alcain, F.J. (2020) SIRT1 and SIRT2 Activity Control in Neurodegenerative Diseases. Frontiers in Pharmacology, 11, Article 585821. https://doi.org/10.3389/fphar.2020.585821 |
| [33] | Zhang, Y., Anoopkumar-Dukie, S. and Davey, A.K. (2021) SIRT1 and SIRT2 Modulators: Potential Anti-Inflamma- tory Treatment for Depression? Biomolecules, 11, Article No. 353. https://doi.org/10.3390/biom11030353 |
| [34] | Kaitsuka, T., Matsushita, M. and Matsushita, N. (2021) Regulation of Hypoxic Signaling and Oxidative Stress via the MicroRNA-SIRT2 Axis and Its Relationship with Aging-Related Dis-eases. Cells, 10, Article No. 3316.
https://doi.org/10.3390/cells10123316 |
| [35] | Fan, Z. and Bin, L. (2022) Will Sirtuin 2 Be a Promising Target for Neuroinflammatory Disorders? Frontiers in Cellular Neuroscience, 16, Article 915587. https://doi.org/10.3389/fncel.2022.915587 |
| [36] | Wu, B., You, S., Qian, H., et al. (2021) The Role of SIRT2 in Vascular-Related and Heart-Related Diseases: A Review. Journal of Cellular and Molecular Medicine, 25, 6470-6478. https://doi.org/10.1111/jcmm.16618 |
| [37] | Gu, W., Cheng, Y., Wang, S., Sun, T. and Li, Z. (2021) PHD Finger Protein 19 Promotes Cardiac Hypertrophy via Epigenetically Regulating SIRT2. Cardiovascular Toxicology, 21, 451-461.
https://doi.org/10.1007/s12012-021-09639-0 |
| [38] | Zheng, M., Du, X., Zhao, L., et al. (2021) Elevated Plasma Sirtuin2 Level Predicts Heart Failure after Acute Myocardial Infarction. Journal of Thoracic Disease, 13, 50-59. https://doi.org/10.21037/jtd-20-2234 |
| [39] | Yang, X., Chang, H.-C., Tatekoshi, Y., et al. (2023) SIRT2 Inhibition Protects against Cardiac Hypertrophy and Heart Failure. BioRxiv. https://doi.org/10.1101/2023.01.25.525524 |
| [40] | Perrini, S., Porro, S., Nigro, P., et al. (2020) Reduced SIRT1 and SIRT2 Expression Promotes Adipogenesis of Human Visceral Adipose Stem Cells and Associates with Accumulation of Visceral Fat in Human Obesity. International Journal of Obesity, 44, 307-319. https://doi.org/10.1038/s41366-019-0436-7 |
| [41] | Arab Sadeghabadi, Z., Ziamajidi, N., Abbasalipourkabir, R., et al. (2018) Garlic (Allium sativum) Increases SIRT1 and SIRT2 Gene Expressions in the Kidney and Liver Tissues of STZ- and STZ+Niacinamide-Induced Diabetic Rats. Journal of Basic and Clinical Physiology and Pharmacology, 29, 463-467. https://doi.org/10.1515/jbcpp-2017-0079 |
