Endothelial nitric oxide synthase in red blood cells: key to a new erythrocrine function?

Endothelial nitric oxide synthase in red blood cells: key to a new erythrocrine function?
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DOI:
10.1016/j.redox.2013.12.027
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发表时间:
2014
期刊:
影响因子:
11.4
通讯作者:
Kelm M
Kelm M
中科院分区:
生物学1区
文献类型:
--
作者:
Cortese-Krott MM;Kelm M

文献摘要

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红细胞(RBC)几乎被认为是组织代谢气体和营养物质的转运体。公认的教条是,RBC通过与氧合血红蛋白快速反应形成高铁血红蛋白和硝酸盐来摄取和吸收内皮衍生的NO,从而限制可用于血管舒张的NO。然而,也已经表明,RBC不仅充当“NO汇”,而且通过合成、运输和释放NO代谢产物和ATP发挥红分泌功能-即RBC的内分泌功能,从而潜在地控制全身NO生物利用度和血管张力。我们和其他实验室最近的工作表明,人红细胞携带活性3型内皮NO合酶(eNOS),在常氧条件下组成性产生NO,其活性在冠状动脉疾病患者中受到损害。在这篇综述中,我们的目的是讨论红细胞eNOS在红细胞信号和功能的潜在作用,并严格修订的证据,到目前为止,非内皮循环eNOS在心血管病理生理学的作用。我们将红细胞分泌功能定义为红细胞分泌信号物质或递质分子的能力。红细胞分泌功能包括清除、转运和产生NO代谢产物和ATP。有体外和体内证据表明红细胞eNOS在信号传导和红细胞分泌功能中的作用。红细胞eNOS和红细胞内分泌功能可能参与器官保护。进一步的研究应该解决红细胞eNOS/RBC信号在心血管健康中的作用。
Red blood cells (RBC) have been considered almost exclusively as a transporter of metabolic gases and nutrients for the tissues. It is an accepted dogma that RBCs take up and inactivate endothelium-derived NO via rapid reaction with oxyhemoglobin to form methemoglobin and nitrate, thereby limiting NO available for vasodilatation. Yet it has also been shown that RBCs not only act as “NO sinks”, but exert an erythrocrine function – i.e an endocrine function of RBC – by synthesizing, transporting and releasing NO metabolic products and ATP, thereby potentially controlling systemic NO bioavailability and vascular tone. Recent work from our and others laboratory demonstrated that human RBCs carry an active type 3, endothelial NO synthase (eNOS), constitutively producing NO under normoxic conditions, the activity of which is compromised in patients with coronary artery disease. In this review we aim to discuss the potential role of red cell eNOS in RBC signaling and function, and to critically revise evidence to this date showing a role of non-endothelial circulating eNOS in cardiovascular pathophysiology. We define erythrocrine function the ability of RBC to secret signaling entities or transmitter momlecules. Erythocrine function include scavenging, transporting and producing NO metabolites and ATP. There is in vitro and in vivo evidence of a role of red cell eNOS in signaling and erythrocrine function. Red cell eNOS and erythocrine function might be involved in organ protection. Further studies should address the role of red cell eNOS/RBC signaling in cardiovascular health.