[1]周媛媛 梁羽.蛋白质O-GlcNAc修饰在心血管疾病的损伤作用[J].心血管病学进展,2025,(3):235.[doi:10.16806/j.cnki.issn.1004-3934.2025.03.010]
　ZHOU Yuanyuan,LIANG Yu.Harmful Effect of Protein O-GlcNAc Modification in Cardiovascular System[J].Advances in Cardiovascular Diseases,2025,(3):235.[doi:10.16806/j.cnki.issn.1004-3934.2025.03.010]
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蛋白质O-GlcNAc修饰在心血管疾病的损伤作用()
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《心血管病学进展》[ISSN:51-1187/R/CN:1004-3934]

卷:
期数:
2025年3期
页码:
235
栏目:
综述
出版日期:
2025-03-25

文章信息/Info

Title:
Harmful Effect of Protein O-GlcNAc Modification in Cardiovascular System
作者:
周媛媛1 梁羽2
(1. 广汉市人民医院麻醉科,四川 德阳 618300 ;2. 四川省医学科学院?四川省人民医院 (电子科技大学附属医院)
Author(s):
ZHOU Yuanyuan; LIANG Yu
(1. Department of Anesthesiology,Guanghan People’s Hospital,Guanghan 618300,Sichuan,China; 2. Department of Anesthesiology, Sichuan Provincial People’s Hospital, Sichuan Academy of Medical Sciences, The Affiliated Hospital of University of Electronic Science and Technology of China,Chengdu 610000, Sichuan,China)
关键词:
O-GlcNAc修饰; 心血管系统; 心力衰竭; 糖尿病心肌病
Keywords:
O-linked -N-acetylglucosamine modification; Cardiovascular system; Heart failure; Diabetic cardiomyopathy
DOI:
10.16806/j.cnki.issn.1004-3934.2025.03.010
摘要:
心脏蛋白质O-连接β-N-乙酰葡萄糖胺（O-GlcNAc）修饰的激活通常与细胞代谢的改变有关，其急性升高可保护心脏免受心脏缺血再灌注损伤，但O-GlcNAc修饰持续激活会对心血管造成不利影响，引起心律失常、心力衰竭、糖尿病心肌病和血管疾病等多种心血管疾病，其主要与心肌钙信号、心肌蛋白、转录因子、内皮型一氧化氮合酶、微RNA的改变等有关。现主要讨论蛋白质O-GlcNAc修饰对心血管的损伤效应及机制研究进展，以期为心血管疾病的治疗提供新思路及药物治疗靶点。
Abstract:
Activation of protein O-linked β-N-acetylglucosamine (O-GlcNAc) modification in heart is often associated with the changes in cell metabolism,the acute increase of protein O-GlcNAc modification protects the heart from ischaemia reperfusion injury,but the continuous activation of O-GlcNAc modification is harmful to cardiovascular function,resulting in multiple cardiovascular diseases,like arrhythmia,heart failure,diabetic cardiomyopathy,and vascular disease,which is related to the changes in myocardial calcium signal,muscle proteins,transcription factors,endothelial nitric oxide synthase,microRNA,and other mechanisms. This article mainly summarizes the research progress on the cardiovascular injury effect and mechanism of O-GlcNAc modification,aiming to provide new insights and drug therapeutic targets for the treatment of cardiovascular diseases

参考文献/References:

[1] Wells L,Hart GW. O-GlcNAcylation:a major nutrient/stress sensor that regulates cellular physiology[J]. J Biol Chem,2024:107635.

[2] Nelson ZM,Leonard GD,Fehl C. Tools for investigating O-GlcNAc in signaling and other fundamental biological pathways[J]. J Biol Chem,2024,300(2):105615.

[3] Ma J,Wu C,Hart GW. Analytical and biochemical perspectives of protein O-GlcNAcylation[J]. Chem Rev,2021,121(3):1513-1581.

[4] Ou W,Liang Y,Qin Y,et al. Hypoxic acclimation improves cardiac redox homeostasis and protects heart against ischemia-reperfusion injury through upregulation of O-GlcNAcylation[J]. Redox Biol,2021,43:101994.

[5] Chatham JC,Patel RP. Protein glycosylation in cardiovascular health and disease[J]. Nature Reviews Cardiology,2024,21(8):525-544.

[6] Umapathi P,Mesubi OO,Banerjee PS,et al. Excessive O-GlcNAcylation causes heart failure and sudden death[J]. Circulation,2021,143(17):1687-1703.

[7] Qiu Z,Cui J,Huang Q,et al. Roles of O-GlcNAcylation in mitochondrial homeostasis and cardiovascular diseases[J]. Antioxidants,2024:13(5):571.

[8] Kadosaka T,Watanabe M,Natsui H,et al. Empagliflozin attenuates arrhythmogenesis in diabetic cardiomyopathy by normalizing intracellular Ca2+ handling in ventricular cardiomyocytes[J]. Am J Physiol Heart Circ Physiol,2023,324(3):H341-H354.

[9] Okolo CA,Khaing EP,Mereacre V,et al. Direct regulation of the cardiac ryanodine receptor (RyR2) by O-GlcNAcylation[J]. Cardiovasc Diabetol,2023,22(1):276.

[10] Umapathi P,Aggarwal A,Zahra F,et al. The multifaceted role of intracellular glycosylation in cytoprotection and heart disease[J]. J Biol Chem,2024,300(6):107296.

[11] Matsuno M,Yokoe S,Nagatsuka T,et al. O-GlcNAcylation-induced GSK-3β activation deteriorates pressure overload-induced heart failure via lack of compensatory cardiac hypertrophy in mice[J]. Front Endocrinol (Lausanne),2023,14:1122125.

[12] Prakoso D,Lim SY,Erickson JR,et al. Fine-tuning the cardiac O-GlcNAcylation regulatory enzymes governs the functional and structural phenotype of the diabetic heart[J]. Cardiovasc Res,2022,118(1):212-225.

[13] Chen Y,Zhao X,Wu H. Metabolic stress and cardiovascular disease in diabetes mellitus:the role of protein O-GlcNAc modification[J]. Arterioscler Thromb Vasc Biol,2019,39(10):1911-1924.

[14] Lou S,Zhu W,Yu T,et al. Compound SJ-12 attenuates streptozocin-induced diabetic cardiomyopathy by stabilizing SERCA2a[J]. Biochim Biophys Acta Mol Basis Dis,2024,1870(5):167140.

[15] Cai L. Prevention or therapy of the diabetic cardiomyopathy by fine O-GlcNAcylation balance:hopes and concerns[J]. Cardiovasc Res,2022,118(1):7-9.

[16] Khanal S,Bhavnani N,Mathias A,et al. Deletion of smooth muscle O-GlcNAc transferase prevents development of atherosclerosis in western diet-fed hyperglycemic ApoE-/- mice in vivo[J]. Int J Mol Sci,2023,24(9):7899.

[17] Zhang W,Sun Y,Yang Y,et al. Impaired intracellular calcium homeostasis enhances protein O-GlcNAcylation and promotes vascular calcification and stiffness in diabetes[J]. Redox Biology,2023,63:102720.

[18] Masaki N,Feng B,Bretón-Romero R,et al. O-GlcNAcylation mediates glucose-induced alterations in endothelial cell phenotype in human diabetes mellitus[J]. J Am Heart Assoc,2020,9(12):e014046.

[19] Dattani A,Singh A,Mccann GP,et al. Myocardial calcium handling in type 2 diabetes:a novel therapeutic target[J]. J Cardiovasc Dev Dis,2024:11(1):12.

[20] Chatham JC,Young ME,Zhang J. Role of O-linked N-acetylglucosamine (O-GlcNAc) modification of proteins in diabetic cardiovascular complications[J]. Curr Opin Pharmacol,2021,57:1-12.

[21] Jankauskas SS,Kansakar U,Varzideh F,et al. Heart failure in diabetes[J]. Metabolism,2021,125:154910.

[22] Hegyi B,Bers DM. New cardiac targets for empagliflozin:O-GlcNAcylation,CaMKⅡ,and calcium handling[J]. Am J Physiol Heart Circ Physiol,2023,324(3):H338-H340.

[23] Hegyi B,Fasoli A,Ko CY,et al. CaMKⅡ serine 280 O-GlcNAcylation links diabetic hyperglycemia to proarrhythmia[J]. Circ Res ,2021,129(1):98-113.

[24] Lu S,Liao Z,Lu X,et al. Hyperglycemia acutely increases cytosolic reactive oxygen species via O-linked GlcNAcylation and CaMKⅡ activation in mouse ventricular myocytes[J]. Circ Res,2020,126(10):e80-e96.

[25] Ng YH,Okolo CA,Erickson JR,et al. Protein O-GlcNAcylation in the heart[J]. Acta Physiol (Oxf),2021,233(1):e13696.

[26] Dozio E,Massaccesi L,Corsi Romanelli MM. Glycation and glycosylation in cardiovascular remodeling:focus on advanced glycation end products and O-linked glycosylations as glucose-related pathogenetic factors and disease markers[J]. J Clin Med,2021,10(20):4792.

[27] Levick SP,Widiapradja A. The diabetic cardiac fibroblast:mechanisms underlying phenotype and function[J]. Int J Mol Sci,2020,21(3):970.

[28] Chen X,Zhang L,He H,et al. Increased O-GlcNAcylation induces myocardial hypertrophy[J]. In Vitro Cell Dev Biol Anim,2020,56(9):735-743.

[29] Yeh CF,Cheng SH,Lin YS,et al. Targeting mechanosensitive endothelial TXNDC5 to stabilize eNOS and reduce atherosclerosis in vivo[J]. Sci Adv,2022,8(3):eabl8096.

[30] Cabrera JT,Si R,Tsuji-Hosokawa A,et al. Restoration of coronary microvascular function by OGA overexpression in a high-fat diet with low-dose streptozotocin-induced type 2 diabetic mice[J]. Diab Vasc Dis Res,2023,20(3):14791641231173630.

[31] Negre-Salvayre A,Swiader A,Guerby P,et al. Post-translational modifications of endothelial nitric oxide synthase induced by oxidative stress in vascular diseases[J]. Redox Experimental Medicine,2022,2022(1):R139-R148.

[32] Aulak KS,Barnes JW,Tian L,et al. Specific O-GlcNAc modification at Ser-615 modulates eNOS function[J]. Redox Biology,2020,36:101625.

[33] Costa TJ,Wilson EW,Fontes MT,et al. The O-GlcNAc dichotomy:when does adaptation become pathological?[J]. Clin Sci (Lond),2023,137(22):1683-1697.

[34] Lo WY,Yang WK,Peng CT,et al. MicroRNA-200a/200b modulate high glucose-induced endothelial inflammation by targeting O-linked N-acetylglucosamine transferase expression[J]. Front Physiol,2018,9:355.

[35] Muthusamy S,Demartino AM,Watson LJ,et al. MicroRNA-539 is up-regulated in failing heart,and suppresses O-GlcNAcase expression[J]. J Biol Chem,2014,289(43):29665-29676.

[36] Tian T,Leng Y,Tang B,et al. The oncogenic role and regulatory mechanism of PGK1 in human non-small cell lung cancer[J]. Biology Direct,2024,19(1):1.

[37] Lee S. Cardiovascular disease and miRNAs:possible oxidative stress-regulating roles of miRNAs[J]. Antioxidants,2024:13(6):656.

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更新日期/Last Update: 2025-04-29