蛋白质翻译后修饰在子痫前期发病机制中的研究进展

doi:10.12280/gjfckx.20230795

摘要/Abstract

摘要：

蛋白质翻译后修饰（post-translational modification）是指蛋白质在翻译后发生的一系列共价修饰，这些修饰能够调控蛋白质的结构和功能，因此对多种疾病的发生和发展产生影响。子痫前期（preeclampsia）是一种妊娠期特有的综合征，病因至今尚不明确。近年研究表明，蛋白质翻译后修饰可能在子痫前期的发病机制中发挥重要作用。综述常见的蛋白质翻译后修饰，如磷酸化、乙酰化、糖基化、泛素化和乳酸化等修饰在子痫前期发病机制中的研究进展，为探讨子痫前期的发病机制和改善诊治措施提供新的方向。

关键词: 先兆子痫, 蛋白质加工, 转译后, 泛素化, 乙酰化作用, 糖基化, 磷酸化, 乳酸化

Abstract:

Protein post-translational modification refers to a series of covalent modifications that occur after protein translation. These modifications can regulate the structure and function of protein, thereby, affecting the development and progression of various diseases. Preeclampsia is a pregnancy-specific syndrome, but the cause of it is still not fully understood. Recent investigations suggest that post-translational modifications of proteins may play a crucial role in the pathogenesis of preeclampsia. In this article, we review the progress of common protein post-translational modifications, such as phosphorylation, acetylation, glycosylation, ubiquitination, and lactypation, in the pathogenesis of preeclampsia, which will provide new directions for exploring the pathogenesis of preeclampsia and for improving diagnostic and therapeutic measures.

Key words: Pre-eclampsia, Protein processing, post-translational, Ubiquitination, Acetylation, Glycosylation, Phosphorylation, Lactylation

陈嘉颖, 冯亚玲. 蛋白质翻译后修饰在子痫前期发病机制中的研究进展[J]. 国际妇产科学杂志, 2024, 51(1): 1-4.

CHEN Jia-ying, FENG Ya-ling. Research Advances on Protein Post-Translational Modification in the Pathogenesis of Preeclampsia[J]. Journal of International Obstetrics and Gynecology, 2024, 51(1): 1-4.

参考文献 32

[1]	中华医学会妇产科学分会妊娠期高血压疾病学组. 妊娠期高血压疾病诊治指南(2020)[J]. 中华妇产科杂志, 2020, 55(4):227-238. doi: 10.3760/cma.j.cn112141-20200114-00039.
[2]	Chappell LC, Cluver CA, Kingdom J, et al. Pre-eclampsia[J]. Lancet, 2021, 398(10297):341-354. doi: 10.1016/S0140-6736(20)32335-7.
[3]	Gestational Hypertension and Preeclampsia: ACOG Practice Bulletin, Number 222[J]. Obstet Gynecol, 2020, 135(6):e237-e260. doi: 10.1097/AOG.0000000000003891.
[4]	孔凡静, 王莉, 杜趁香, 等. 子痫前期发生的危险因素及孕中期血清PLGF、sFlt-1、ET-1水平的临床预测价值[J]. 实验与检验医学, 2022, 40(5):572-575,580. doi: 10.3969/j.issn.1674-1129.2022.05.013.
[5]	梁结明, 刘国成. 子痫前期发病机制的研究进展[J]. 国际妇产科学杂志, 2023, 50(4):405-408,420. doi: 10.12280/gjfckx.20230106.
[6]	Samaržija I. Post-Translational Modifications That Drive Prostate Cancer Progression[J]. Biomolecules, 2021, 11(2):247. doi: 10.3390/biom11020247.
[7]	Newcombe EA, Delaforge E, Hartmann-Petersen R, et al. How phosphorylation impacts intrinsically disordered proteins and their function[J]. Essays Biochem, 2022, 66(7):901-913. doi: 10.1042/EBC20220060. pmid: 36350035
[8]	Ijomone OM, Iroegbu JD, Aschner M, et al. Impact of environmental toxicants on p38- and ERK-MAPK signaling pathways in the central nervous system[J]. Neurotoxicology, 2021, 86:166-171. doi: 10.1016/j.neuro.2021.08.005. pmid: 34389354
[9]	郭辉. 磷酸化丝裂原蛋白活化激酶P38、肿瘤坏死因子-α、核因子-κB p65与妊娠期高血压疾病关系的研究[D]. 石家庄: 河北医科大学, 2010.
[10]	Fitzgerald JS, Busch S, Wengenmayer T, et al. Signal transduction in trophoblast invasion[J]. Chem Immunol Allergy, 2005, 88:181-199. doi: 10.1159/000087834. pmid: 16129946
[11]	Hu M, Zheng Y, Liao J, et al. miR21 modulates the Hippo signaling pathway via interference with PP2A Bβ to inhibit trophoblast invasion and cause preeclampsia[J]. Mol Ther Nucleic Acids, 2022, 30:143-161. doi: 10.1016/j.omtn.2022.09.006.
[12]	Park J, Cho J, Song EJ. Ubiquitin-proteasome system (UPS) as a target for anticancer treatment[J]. Arch Pharm Res, 2020, 43(11):1144-1161. doi: 10.1007/s12272-020-01281-8. pmid: 33165832
[13]	蒋寒宇, 顾文文, 王健. 母胎界面的蛋白质泛素化修饰及其与病理妊娠相关性的研究进展[J]. 生殖医学杂志, 2022, 31(5):701-706. doi: 10.3969/j.issn.1004-3845.2022.05.022.
[14]	Choudhury J, Pandey D, Chaturvedi PK, et al. Epigenetic regulation of epithelial to mesenchymal transition: a trophoblast perspective[J]. Mol Hum Reprod, 2022, 28(5):gaac013. doi: 10.1093/molehr/gaac013.
[15]	Wu D, Shi L, Chen X, et al. β-TrCP suppresses the migration and invasion of trophoblast cells in preeclampsia by down-regulating Snail[J]. Exp Cell Res, 2020, 395(2):112230. doi: 10.1016/j.yexcr.2020.112230.
[16]	Chen G, Chen L, Huang Y, et al. Increased FUN14 domain containing 1 (FUNDC1) ubiquitination level inhibits mitophagy and alleviates the injury in hypoxia-induced trophoblast cells[J]. Bioengineered, 2022, 13(2):3620-3633. doi: 10.1080/21655979.2021.1997132.
[17]	Chiang MH, Liang FY, Chen CP, et al. Mechanism of hypoxia-induced GCM1 degradation: implications for the pathogenesis of preeclampsia[J]. J Biol Chem, 2009, 284(26):17411-17419. doi: 10.1074/jbc.M109.016170.
[18]	Shvedunova M, Akhtar A. Modulation of cellular processes by histone and non-histone protein acetylation[J]. Nat Rev Mol Cell Biol, 2022, 23(5):329-349. doi: 10.1038/s41580-021-00441-y.
[19]	Zhang B, Kim MY, Elliot G, et al. Human placental cytotrophoblast epigenome dynamics over gestation and alterations in placental disease[J]. Dev Cell, 2021, 56(9):1238-1252.e5. doi: 10.1016/j.devcel.2021.04.001. pmid: 33891899
[20]	Hu B, Li D, Tang D, et al. Integrated proteome and acetylome analyses unveil protein features of gestational diabetes mellitus and preeclampsia[J]. Proteomics, 2022, 22(22):e2200124. doi: 10.1002/pmic.202200124.
[21]	Xiong L, Ye X, Chen Z, et al. Advanced Maternal Age-associated SIRT1 Deficiency Compromises Trophoblast Epithelial-Mesenchymal Transition through an Increase in Vimentin Acetylation[J]. Aging Cell, 2021, 20(10):e13491. doi: 10.1111/acel.13491.
[22]	Peng W, Liu Y, Qi H, et al. Alpha-actinin-4 is essential for maintaining normal trophoblast proliferation and differentiation during early pregnancy[J]. Reprod Biol Endocrinol, 2021, 19(1):48. doi: 10.1186/s12958-021-00733-0.
[23]	Shangguan Y, Wang Y, Shi W, et al. Systematic proteomics analysis of lysine acetylation reveals critical features of placental proteins in pregnant women with preeclampsia[J]. J Cell Mol Med, 2021, 25(22):10614-10626. doi: 10.1111/jcmm.16997. pmid: 34697885
[24]	李佳丽. 蛋白质糖基化与疾病关系的研究进展[J]. 海南医学, 2023, 34(4):589-592. doi: 10.3969/j.issn.1003-6350.2023.04.028.
[25]	Flood-Nichols SK, Kazanjian AA, Tinnemore D, et al. Aberrant glycosylation of plasma proteins in severe preeclampsia promotes monocyte adhesion[J]. Reprod Sci, 2014, 21(2):204-214. doi: 10.1177/1933719113492210. pmid: 23757314
[26]	Dos Passos Junior RR, de Freitas RA, Dela Justina V, et al. Protein O-GlcNAcylation as a nutrient sensor signaling placental dysfunction in hypertensive pregnancy[J]. Front Endocrinol(Lausanne), 2022, 13:1032499. doi: 10.3389/fendo.2022.1032499.
[27]	Yang M, Li H, Rong M, et al. Dysregulated GLUT1 may be involved in the pathogenesis of preeclampsia by impairing decidualization[J]. Mol Cell Endocrinol, 2022, 540:111509. doi: 10.1016/j.mce.2021.111509.
[28]	Herghelegiu CG, Veduta A, Stefan MF, et al. Hyperglycosylated-hCG: Its Role in Trophoblast Invasion and Intrauterine Growth Restriction[J]. Cells, 2023, 12(12):1647. doi: 10.3390/cells12121647.
[29]	Zhang D, Tang Z, Huang H, et al. Metabolic regulation of gene expression by histone lactylation[J]. Nature, 2019, 574(7779):575-580. doi: 10.1038/s41586-019-1678-1.
[30]	Li X, Yang N, Wu Y, et al. Hypoxia regulates fibrosis-related genes via histone lactylation in the placentas of patients with preeclampsia[J]. J Hypertens, 2022, 40(6):1189-1198. doi: 10.1097/HJH.0000000000003129. pmid: 35703881
[31]	Zou L, Yang Y, Wang Z, et al. Lysine Malonylation and Its Links to Metabolism and Diseases[J]. Aging Dis, 2023, 14(1):84-98. doi: 10.14336/AD.2022.0711.
[32]	Bruning U, Morales-Rodriguez F, Kalucka J, et al. Impairment of Angiogenesis by Fatty Acid Synthase Inhibition Involves mTOR Malonylation[J]. Cell Metab, 2018, 28(6):866-880.e15. doi: 10.1016/j.cmet.2018.07.019. pmid: 30146486