摘要
棕榈酰化修饰是一种可逆的蛋白质翻译后修饰方式,主要由棕榈酰基转移酶和去棕榈酰化酶共同调节目标蛋白质上特定半胱氨酸残基的棕榈酰化水平,从而调控蛋白质的稳定性、亚细胞定位和信号转导。近年来,棕榈酰化修饰在心血管疾病(CVDs)中的作用备受关注。棕榈酰化修饰通过动态调控钠钙交换体1、电压门控钾离子通道、电压门控钠离子通道促进心律失常的发生发展;棕榈酰化修饰参与内皮细胞功能障碍、巨噬细胞脂质代谢、血管平滑肌细胞迁移等环节的调控,促进冠状动脉粥样硬化的发生发展;棕榈酰化修饰间接作用于β-AR信号通路、心肌细胞钙调控通路及心肌纤维化相关信号通路,促进心力衰竭发生发展。深入探究棕榈酰化修饰在CVDs发生发展中的具体作用机制,有助于寻找新的CVDs治疗靶点,为CVDs精准治疗策略提供依据。
Protein palmitoylation is a reversible post-translational modification,dynamically regulated by the opposing actions of palmitoyltransferases and depalmitoylases.This process modulates the palmitoylation levels of specific cysteine residues on target proteins,thereby modulating protein stability,subcellular localization,and signal transduction functions.In recent years,the role of palmitoylation in the pathogenesis and progression of cardiovascular diseases(CVDs)has garnered significant attention.Accumulating evidence indicates that palmitoylation contributes to arrhythmogenesis by dynamically regulating the sodium-calcium exchanger(NCX1)and voltage-gated potassium/sodium channels.It also promotes the development of coronary atherosclerosis by influencing endothelial dysfunction,macrophage lipid metabolism,and vascular smooth muscle cell migration.Furthermore,palmitoylation exacerbates heart failure progression through indirect modulation ofβ-adrenergic receptor(β-AR)signaling,cardiomyocyte calcium handling,and pro-fibrotic pathways.This review aims to explore the functional roles and regulatory mechanisms of protein palmitoylation in CVDs,which may facilitate the identification of novel therapeutic targets and provide a theoretical foundation for precision medicine in cardiovascular disease.
作者
张雪萍
谭昭充
ZHANG Xueping;TAN Zhaochong(College of Pharmacy,Yichun University,Yichun 336000,China)
出处
《山东医药》
2025年第9期135-138,143,共5页
Shandong Medical Journal
