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在衰老过程中,ZFYVE21促进脏内皮氧化信号传递和血管屏障功能

Quan Jiang¹, Guiyu Song², Liying He³

¹Section of Cardiovascular Medicine, Yale University School of Medicine, New Haven, Connecticut, USA; Department of Cardiology, West Haven VA Medical Center, West Haven, Connecticut, USA.

Kidney international

|May 26, 2024

概括

蛋白质ZFYVE21对于维持衰老中的功能至关重要. 它在内皮细胞 (ECs) 的下降加速衰老,并通过影响氧化 (NO) 活性,损害脏健康.

科学领域:

内分泌学在内分泌学.
腎臟病學 (nephrology) 是一種醫學.
细胞生物学细胞生物学

背景情况:

ZFYVE21是一种内分体关联蛋白,在内皮细胞 (ECs) 中高度表达.
它的体内功能,特别是在衰老的脏中,仍然在很大程度上未被定义.
内皮细胞功能对于维持血管完整性和器官健康至关重要.

研究的目的:

调查ZFYVE21在调节衰老脏中的血管屏障功能的作用.
阐明ZFYVE21影响内皮细胞功能和氧化 (NO) 活性的分子机制.
确定针对ZFYVE21针对与年龄相关的功能障碍的治疗潜力.

主要方法:

产生内皮细胞特异性的Zfyve21淘汰赛小鼠 (Zfyve21 EC-/-).
评估功能,血管完整性和敲击和野生类型小鼠的衰老表型.
活细胞成像和人类脏器官培养来研究ZFYVE21介导的蛋白质贩运和NO监管.

主要成果:

在老年人和老鼠脏中,ZFYVE21水平下降.
特定于欧洲共同体的Zfyve21淘汰赛小鼠表现出加速衰老,内皮氧化合成酶 (eNOS) 活性降低和功能不全.
ZFYVE21的损失导致了间歇性和球EC损伤,可以通过NO捐赠者部分挽救.
ZFYVE21促进了eNOS转移到Rab5+囊泡中,减少了抑制性的caveolin-1并维持了eNOS活动.

结论:

在衰老过程中,ZFYVE21是血管屏障功能和脏健康的重要调节者.
一个ZFYVE21介导的蛋白质贩运途径维持了内皮氧化合成酶 (eNOS) 的活性.
这条通路对于维持功能和预防与年龄相关的损伤至关重要.

关键词:

恩诺斯 (ENOS) 是一个人.衰老的衰老衰老的衰老内分泌体内分泌体内分泌体内分泌体内皮细胞功能障碍内皮细胞功能障碍

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