结核与肺部疾病杂志 ›› 2023, Vol. 4 ›› Issue (2): 164-168.doi: 10.19983/j.issn.2096-8493.20230016
收稿日期:
2023-01-09
出版日期:
2023-04-20
发布日期:
2023-04-07
通信作者:
常春,Email:Received:
2023-01-09
Online:
2023-04-20
Published:
2023-04-07
Contact:
Chang Chun, Email: 摘要:
神经酰胺是鞘脂代谢的中心,也是一种重要的信号分子,参与细胞分化、增殖、凋亡和迁移等多种生物功能。神经酰胺合成酶介导神经酰胺的合成。哮喘是一种以气流阻塞、气道高反应性和肺部炎症为特征的慢性气道疾病,极大地影响了患者的生活质量,是重要的公共卫生问题。研究表明,神经酰胺在哮喘的病理生理发展中发挥重要作用。本文重点讨论神经酰胺对参与哮喘发病的多种细胞的影响,以及不同种类神经酰胺作用的差异性,以期为人们更好地了解哮喘及寻找哮喘潜在治疗靶点提供理论基础。
中图分类号:
胡亭亭, 常春. 神经酰胺及神经酰胺合成酶在哮喘中的作用[J]. 结核与肺部疾病杂志, 2023, 4(2): 164-168. doi: 10.19983/j.issn.2096-8493.20230016
Hu Tingting, Chang Chun. The role of ceramide and ceramide synthetase in asthma[J]. Journal of Tuberculosis and Lung Disease, 2023, 4(2): 164-168. doi: 10.19983/j.issn.2096-8493.20230016
[1] |
Huang K, Yang T, Xu J, et al. Prevalence, risk factors, and management of asthma in China: a national cross-sectional study. Lancet, 2019, 394(10196): 407-418. doi:10.1016/S0140-6736(19)31147-X.
doi: S0140-6736(19)31147-X pmid: 31230828 |
[2] |
Dharmage SC, Perret JL, Custovic A. Epidemiology of Asthma in Children and Adults. Front Pediatr, 2019, 7: 246. doi:10.3389/fped.2019.00246.
doi: 10.3389/fped.2019.00246 pmid: 31275909 |
[3] |
Chaurasia B, Summers SA. Ceramides in Metabolism: Key Lipotoxic Players. Annu Rev Physiol, 2021, 83: 303-330. doi:10.1146/annurev-physiol-031620-093815.
doi: 10.1146/annurev-physiol-031620-093815 pmid: 33158378 |
[4] |
Levy M, Futerman AH. Mammalian ceramide synthases. IUBMB life, 2010, 62(5): 347-356. doi:10.1002/iub.319.
doi: 10.1002/iub.319 pmid: 20222015 |
[5] |
Tidhar R, Zelnik ID, Volpert G, et al. Eleven residues determine the acyl chain specificity of ceramide synthases. J Biol Chem, 2018, 293(25): 9912-9921. doi:10.1074/jbc.RA118.001936.
doi: 10.1074/jbc.RA118.001936 pmid: 29632068 |
[6] |
Garic'D, De Sanctis JB, Shah J, et al. Biochemistry of very-long-chain and long-chain ceramides in cystic fibrosis and other diseases: The importance of side chain. Prog Lipid Res, 2019, 74: 130-144. doi:10.1016/j.plipres.2019.03.001.
doi: S0163-7827(19)30011-6 pmid: 30876862 |
[7] |
Agache I, Akdis CA. Endotypes of allergic diseases and asthma: An important step in building blocks for the future of precision medicine. Allergol Int, 2016, 65(3): 243-252. doi:10.1016/j.alit.2016.04.011.
doi: 10.1016/j.alit.2016.04.011 pmid: 27282212 |
[8] |
Sofi MH, Heinrichs J, Dany M, et al. Ceramide synthesis regulates T cell activity and GVHD development. JCI insight, 2017, 2(10): e91701. doi:10.1172/jci.insight.91701.
doi: 10.1172/jci.insight.91701 URL |
[9] |
Shin SH, Cho KA, Yoon HS, et al. Ceramide Synthase 2 Null Mice Are Protected from Ovalbumin-Induced Asthma with Higher T Cell Receptor Signal Strength in CD4+ T Cells. Int J Mol Sci, 2021, 22(5):2713. doi:10.3390/ijms22052713.
doi: 10.3390/ijms22052713 URL |
[10] |
Robinson GA, Waddington KE, Pineda-Torra I, et al. Transcriptional Regulation of T-Cell Lipid Metabolism: Implications for Plasma Membrane Lipid Rafts and T-Cell Function. Front Immunol, 2017, 8: 1636. doi:10.3389/fimmu.2017.01636.
doi: 10.3389/fimmu.2017.01636 pmid: 29225604 |
[11] |
Hammad H, Lambrecht BN. The basic immunology of asthma. Cell, 2021, 184(6): 1469-1485. doi:10.1016/j.cell.2021.02.016.
doi: 10.1016/j.cell.2021.02.016 pmid: 33711259 |
[12] |
Kim SH, Jung HW, Kim M, et al. Ceramide/sphingosine-1-phosphate imbalance is associated with distinct inflammatory phenotypes of uncontrolled asthma. Allergy, 2020, 75(8): 1991-2004. doi:10.1111/all.14236.
doi: 10.1111/all.14236 URL |
[13] |
James BN, Oyeniran C, Sturgill JL, et al. Ceramide in apoptosis and oxidative stress in allergic inflammation and asthma. J Allergy Clin Immunol, 2021, 147(5): 1936-1948.e9. doi:10.1016/j.jaci.2020.10.024.
doi: 10.1016/j.jaci.2020.10.024 URL |
[14] |
Kamocki K, Van Demark M, Fisher A, et al. RTP801 is required for ceramide-induced cell-specific death in the murine lung. Am J Respir Cell Mol Biol, 2013, 48(1): 87-93. doi:10.1165/rcmb.2012-0254OC.
doi: 10.1165/rcmb.2012-0254OC URL |
[15] |
Ono JG, Worgall TS, Worgall S. Airway reactivity and sphingolipids-implications for childhood asthma. Mol Cell Pediatr, 2015, 2(1): 13. doi:10.1186/s40348-015-0025-3.
doi: 10.1186/s40348-015-0025-3 pmid: 26637347 |
[16] |
Nakamura Y, Nakashima S, Ojio K, et al. Ceramide inhibits IgE-mediated activation of phospholipase D, but not of phospholipase C, in rat basophilic leukemia (RBL-2H3) cells. J Immunol, 1996, 156(1): 256-262.
pmid: 8598470 |
[17] |
Izawa K, Yamanishi Y, Maehara A, et al. The receptor LMIR3 negatively regulates mast cell activation and allergic responses by binding to extracellular ceramide. Immunity, 2012, 37(5): 827-839. doi:10.1016/j.immuni.2012.08.018.
doi: 10.1016/j.immuni.2012.08.018 pmid: 23123064 |
[18] |
Robida PA, Chumanevich AP, Gandy AO, et al. Skin Mast Cell-Driven Ceramides Drive Early Apoptosis in Pre-Symptoma-tic Eczema in Mice. Int J Mol Sci, 2021, 22(15): 7815. doi:10.3390/ijms22157851.
doi: 10.3390/ijms22157851 URL |
[19] |
Itakura A, Tanaka A, Aioi A, et al. Ceramide and sphingosine rapidly induce apoptosis of murine mast cells supported by interleukin-3 and stem cell factor. Exp Hematol, 2002, 30(3): 272-278. doi:10.1016/s0301-472x(01)00790-1.
doi: 10.1016/s0301-472x(01)00790-1 pmid: 11882365 |
[20] |
Lambrecht BN, Hammad H. The airway epithelium in asthma. Nat Med, 2012, 18(5):684-692. doi:10.1038/nm.2737.
doi: 10.1038/nm.2737 pmid: 22561832 |
[21] |
Juncadella IJ, Kadl A, Sharma AK, et al. Apoptotic cell clearance by bronchial epithelial cells critically influences airway inflammation. Nature, 2013, 493(7433): 547-551. doi:10.1038/nature11714.
doi: 10.1038/nature11714 |
[22] |
Teichgräber V, Ulrich M, Endlich N, et al. Ceramide accumulation mediates inflammation, cell death and infection susceptibility in cystic fibrosis. Nat Med, 2008, 14(4): 382-391. doi:10.1038/nm1748.
doi: 10.1038/nm1748 pmid: 18376404 |
[23] |
Thomas RL Jr, Matsko CM, Lotze MT, et al. Mass spectrometric identification of increased C 16 ceramide levels during apoptosis. J Biol Chem, 1999, 274(43): 30580-30588. doi:10.1074/jbc.274.43.30580.
doi: 10.1074/jbc.274.43.30580 pmid: 10521441 |
[24] |
Kothari PH, Qiu W, Croteau-Chonka DC, et al. Role of local CpG DNA methylation in mediating the 17q 21 asthma susceptibility gasdermin B (GSDMB)/ORMDL sphingolipid biosynthesis regulator 3 (ORMDL3) expression quantitative trait locus. J Allergy Clin Immunol, 2018, 141(6): 2282-2286.e6. doi:10.1016/j.jaci.2017.11.057.
doi: S0091-6749(18)30112-X pmid: 29374573 |
[25] |
Breslow DK, Collins SR, Bodenmiller B, et al. Orm family proteins mediate sphingolipid homeostasis. Nature, 2010, 463(7284): 1048-1053. doi:10.1038/nature08787.
doi: 10.1038/nature08787 |
[26] |
Worgall TS. Sphingolipids, ORMDL3 and asthma: what is the evidence? Curr Opin Clin Nutr Metab Care, 2017, 20(2): 99-103. doi:10.1097/MCO.0000000000000349.
doi: 10.1097/MCO.0000000000000349 URL |
[27] |
Oyeniran C, Sturgill JL, Hait NC, et al. Aberrant ORM (yeast)-like protein isoform 3 (ORMDL3) expression dysregulates ceramide homeostasis in cells and ceramide exacerbates allergic asthma in mice. J Allergy Clin Immunol, 2015, 136(4): 1035-1046.e6. doi:10.1016/j.jaci.2015.02.031.
doi: 10.1016/j.jaci.2015.02.031 pmid: 25842287 |
[28] |
Siow D, Sunkara M, Dunn TM, et al. ORMDL/serine palmitoyltransferase stoichiometry determines effects of ORMDL 3 expression on sphingolipid biosynthesis. J Lipid Res, 2015, 56(4): 898-908. doi:10.1194/jlr.M057539.
doi: 10.1194/jlr.M057539 URL |
[29] |
Miller M, Rosenthal P, Beppu A, et al. Oroscomucoid like protein 3 (ORMDL3) transgenic mice have reduced levels of sphingolipids including sphingosine-1-phosphate and ceramide. J Allergy Clin Immunol, 2017, 139(4): 1373-1376.e4. doi:10.1016/j.jaci.2016.08.053.
doi: S0091-6749(16)31272-6 pmid: 27826095 |
[30] |
Grösch S, Schiffmann S, Geisslinger G. Chain length-specific properties of ceramides. Prog Lipid Res, 2012, 51(1): 50-62. doi:10.1016/j.plipres.2011.11.001.
doi: 10.1016/j.plipres.2011.11.001 pmid: 22133871 |
[31] |
Pullmannová P, Pavlíková L, Kovácˇik A, et al. Permeability and microstructure of model stratum corneum lipid membranes containing ceramides with long (C16) and very long (C24) acyl chains. Biophys Chem, 2017, 224: 20-31. doi:10.1016/j.bpc.2017.03.004.
doi: S0301-4622(16)30463-X pmid: 28363088 |
[32] |
Siskind LJ, Kolesnick RN, Colombini M. Ceramide channels increase the permeability of the mitochondrial outer membrane to small proteins. J Biol Chem, 2002, 277(30): 26796-26803. doi:10.1074/jbc.M200754200.
doi: 10.1074/jbc.M200754200 pmid: 12006562 |
[33] |
Stiban J, Perera M. Very long chain ceramides interfere with C16-ceramide-induced channel formation: A plausible mechanism for regulating the initiation of intrinsic apoptosis. Biochim Biophys Acta, 2015, 1848(2): 561-567. doi:10.1016/j.bbamem.2014.11.018.
doi: 10.1016/j.bbamem.2014.11.018 pmid: 25462172 |
[34] |
Imgrund S, Hartmann D, Farwanah H, et al. Adult ceramide synthase 2 (CERS2)-deficient mice exhibit myelin sheath defects, cerebellar degeneration, and hepatocarcinomas. J Biol Chem, 2009, 284(48): 33549-33560. doi:10.1074/jbc.M109.031971.
doi: 10.1074/jbc.M109.031971 pmid: 19801672 |
[35] |
Petrache I, Kamocki K, Poirier C, et al. Ceramide synthases expression and role of ceramide synthase-2 in the lung: insight from human lung cells and mouse models. PLoS One, 2013, 8(5): e62968. doi:10.1371/journal.pone.0062968.
doi: 10.1371/journal.pone.0062968 URL |
[36] |
Pewzner-Jung Y, Park H, Laviad EL, et al. A critical role for ceramide synthase 2 in liver homeostasis: I. alterations in lipid metabolic pathways. J Biol Chem, 2010, 285(14): 10902-10910. doi:10.1074/jbc.M109.077594.
doi: 10.1074/jbc.M109.077594 pmid: 20110363 |
[37] |
Petrache I, Petrusca DN. The involvement of sphingolipids in chronic obstructive pulmonary diseases. Handb Exp Pharmacol, 2013 (216): 247-264. doi:10.1007/978-3-7091-1511-4_12.
doi: 10.1007/978-3-7091-1511-4_12 pmid: 23563660 |
[38] |
Choi Y, Kim M, Kim SJ, et al. Metabolic shift favoring C18:0 ceramide accumulation in obese asthma. Allergy, 2020, 75(11): 2858-2866. doi:10.1111/all.14366.
doi: 10.1111/all.14366 URL |
[39] |
Hartmann D, Lucks J, Fuchs S, et al. Long chain ceramides and very long chain ceramides have opposite effects on human breast and colon cancer cell growth. Int J Biochem Cell Biol, 2012, 44(4): 620-628. doi:10.1016/j.biocel.2011.12.019.
doi: 10.1016/j.biocel.2011.12.019 pmid: 22230369 |
[40] |
Kajander K, Myllyluoma E, Kyrönpalo S, et al. Elevated pro-inflammatory and lipotoxic mucosal lipids characterise irritable bowel syndrome. World J Gastroenterol, 2009, 15(48): 6068-6074. doi:10.3748/wjg.15.6068.
doi: 10.3748/wjg.15.6068 URL |
[1] | 黄俊文, 陈颖, 蔡绍曦, 赵海金. 靶向哮喘气道上皮研究进展[J]. 结核与肺部疾病杂志, 2023, 4(2): 153-157. |
[2] | 王忠照, 唐昊. 哮喘的气道重构机制研究进展[J]. 结核与肺部疾病杂志, 2023, 4(2): 158-163. |
[3] | 李锡容, 谢佳星. 开展哮喘的多学科管理 提高哮喘的诊治水平[J]. 结核与肺部疾病杂志, 2023, 4(2): 93-97. |
[4] | 任坦坦, 詹森林, 王玉香, 喻宏, 郑俊峰, 杨敏, 邓国防, 张培泽. PD-1/PD-L1抑制剂相关活动性结核病的临床特点及文献复习[J]. 结核与肺部疾病杂志, 2023, 4(1): 27-32. |
[5] | 闫金燕, 李小敏, 马香. 儿童哮喘与百日咳关系机制的研究进展[J]. 结核与肺部疾病杂志, 2023, 4(1): 78-84. |
[6] | 黄威, 沈银忠. 艾滋病合并结核病诊治中的关键问题[J]. 结核与肺部疾病杂志, 2022, 3(6): 431-436. |
[7] | 娄南南, 郭晶, 马香, 盖中涛. 咳嗽变异性哮喘病理机制及治疗的研究进展[J]. 结核与肺部疾病杂志, 2022, 3(6): 521-525. |
[8] | 郑惠文, 李飞娜, 申晨. 儿童耐药结核病诊治研究进展[J]. 结核与肺部疾病杂志, 2022, 3(5): 402-404. |
[9] | 张春华, 陈伟. 儿童结核病流行现状与经济负担研究进展[J]. 结核与肺部疾病杂志, 2022, 3(5): 405-409. |
[10] | 刘原园, 李璐, 吴托雅, 鲁洁. 结核分枝杆菌Mce4蛋白家族研究进展[J]. 结核与肺部疾病杂志, 2022, 3(5): 415-419. |
[11] | 刘琳琳, 王秀芬, 姜游力, 桂敏, 陈敬芳. 肺结核后肺病患者肺康复训练的应用进展[J]. 结核与肺部疾病杂志, 2022, 3(5): 420-424. |
[12] | 郦源, 郭茹茹, 吕良敬. 结缔组织病合并结核病的研究进展[J]. 结核与肺部疾病杂志, 2022, 3(4): 309-314. |
[13] | 张晓林, 李锋. 肺结核致呼吸衰竭研究进展[J]. 结核与肺部疾病杂志, 2022, 3(4): 320-324. |
[14] | 林慧敏, 符昱, 方章福, 谢佳星. 嗜酸性粒细胞哮喘的研究进展[J]. 结核与肺部疾病杂志, 2022, 3(4): 328-333. |
[15] | 周伊南, 朱惠莉. 慢性阻塞性肺疾病合并肺结核的研究进展[J]. 结核与肺部疾病杂志, 2022, 3(4): 338-342. |
阅读次数 | ||||||
全文 |
|
|||||
摘要 |
|
|||||