Lysis of human erythrocytes due to Piezo1-dependent cytosolic calcium overload as a mechanism of circulatory removal

胞浆 机制(生物学) 溶解 化学 循环系统 细胞生物学 压电1 生物物理学 生物化学 生物 医学 内科学 受体 认识论 哲学 有机化学 离子通道 机械敏感通道
作者
Lennart Kuck,Antony P. McNamee,Maria Bordukova,Ario Sadafi,Carsten Marr,Jason N. Peart,Michael J. Simmonds
出处
期刊:Proceedings of the National Academy of Sciences of the United States of America [Proceedings of the National Academy of Sciences]
卷期号:121 (36) 被引量:2
标识
DOI:10.1073/pnas.2407765121
摘要

Hematopoietic stem cells surrender organelles during differentiation, leaving mature red blood cells (RBC) devoid of transcriptional machinery and mitochondria. The resultant absence of cellular repair capacity limits RBC circulatory longevity, and old cells are removed from circulation. The specific age-dependent alterations required for this apparently targeted removal of RBC, however, remain elusive. Here, we assessed the function of Piezo1, a stretch-activated transmembrane cation channel, within subpopulations of RBC isolated based on physical properties associated with aging. We subsequently investigated the potential role of Piezo1 in RBC removal, using pharmacological and mechanobiological approaches. Dense (old) RBC were separated from whole blood using differential density centrifugation. Tolerance of RBC to mechanical forces within the physiological range was assessed on single-cell and cell population levels. Expression and function of Piezo1 were investigated in separated RBC populations by monitoring accumulation of cytosolic Ca 2+ and changes in cell morphology in response to pharmacological Piezo1 stimulation and in response to physical forces. Despite decreased Piezo1 activity with increasing cell age, tolerance to prolonged Piezo1 stimulation declined sharply in older RBC, precipitating lysis. Cell lysis was immediately preceded by an acute reversal of density. We propose a Piezo1-dependent mechanism by which RBC may be removed from circulation: Upon adherence of these RBC to other tissues, they are uniquely exposed to prolonged mechanical forces. The resultant sustained activation of Piezo1 leads to a net influx of Ca 2+ , overpowering the Ca 2+ -removal capacity of specifically old RBC, which leads to reversal of ion gradients, dysregulated cell hydration, and ultimately osmotic lysis.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
通通真行完成签到,获得积分10
刚刚
zy完成签到,获得积分10
刚刚
猪猪玉完成签到 ,获得积分10
刚刚
烟花应助LXXue采纳,获得10
刚刚
云云发布了新的文献求助10
刚刚
正直帆布鞋完成签到,获得积分10
刚刚
空白完成签到,获得积分10
1秒前
叶子完成签到,获得积分10
1秒前
夜猫酱酱子完成签到,获得积分10
1秒前
于于于完成签到,获得积分20
1秒前
Owen应助猪肉炖粉条采纳,获得10
2秒前
LCC完成签到 ,获得积分10
2秒前
852应助博修采纳,获得10
4秒前
jiangfei完成签到,获得积分10
4秒前
乐观寒珊发布了新的文献求助20
4秒前
赵文若完成签到,获得积分20
4秒前
巫马夜安完成签到,获得积分10
5秒前
caicai完成签到 ,获得积分10
5秒前
谦让青发布了新的文献求助10
6秒前
小麦完成签到,获得积分10
6秒前
我一拳打树上完成签到,获得积分10
7秒前
zy_完成签到,获得积分10
7秒前
积极的尔竹完成签到,获得积分10
7秒前
7秒前
8秒前
啦啦啦完成签到,获得积分10
8秒前
酷波er应助矿泉水采纳,获得10
9秒前
小爽完成签到,获得积分10
9秒前
9秒前
逢春完成签到,获得积分10
9秒前
哈尼完成签到,获得积分10
9秒前
荡秋千的猴子完成签到,获得积分10
9秒前
浮名半生完成签到,获得积分10
10秒前
edtaa完成签到 ,获得积分10
10秒前
11秒前
思源应助科研通管家采纳,获得10
11秒前
zho应助科研通管家采纳,获得10
11秒前
迟大猫应助科研通管家采纳,获得10
11秒前
wanci应助科研通管家采纳,获得10
11秒前
李爱国应助科研通管家采纳,获得10
12秒前
高分求助中
Continuum Thermodynamics and Material Modelling 3000
Production Logging: Theoretical and Interpretive Elements 2700
Mechanistic Modeling of Gas-Liquid Two-Phase Flow in Pipes 2500
Structural Load Modelling and Combination for Performance and Safety Evaluation 800
Conference Record, IAS Annual Meeting 1977 610
Virulence Mechanisms of Plant-Pathogenic Bacteria 500
白土三平研究 500
热门求助领域 (近24小时)
化学 材料科学 生物 医学 工程类 有机化学 生物化学 物理 纳米技术 计算机科学 内科学 化学工程 复合材料 基因 遗传学 物理化学 催化作用 量子力学 光电子学 冶金
热门帖子
关注 科研通微信公众号,转发送积分 3556082
求助须知:如何正确求助?哪些是违规求助? 3131635
关于积分的说明 9392313
捐赠科研通 2831483
什么是DOI,文献DOI怎么找? 1556442
邀请新用户注册赠送积分活动 726605
科研通“疑难数据库(出版商)”最低求助积分说明 715912