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磷酸果糖激酶同工酶调控存储红细胞的能量状态和输血效果
作者:小柯机器人 发布时间:2024/7/7 15:32:54

美国科罗拉多大学丹佛-安舒茨医学院Angelo D’Alessandro研究组在研究中取得进展。他们发现了糖酵解的生物和遗传决定因素——磷酸果糖激酶同工酶促进储存红细胞(RBC)的能量状态和输血效果。2024年7月3日,国际学术期刊《细胞-代谢》发表了这一成果。

研究人员利用 "接受者流行病学和捐献者评估研究"中包涵的13,029名志愿者,确定了储存末期糖酵解代谢物的水平与捐献者年龄、性别和种族特异性基因多态性之间的关系,这些基因多态性分布在血小板磷酸果激酶1(在成熟红细胞中检测到)、己糖激酶1(HK1)和ADP核糖基环化酶1和2(CD38/BST1)的编码区域。

基因-代谢物关联在新鲜和存储的525只多样性杂交小鼠的红细胞中得到了验证,并对来自643个人的1,929个存储红细胞样本进行了多组学表征。ATP和次黄嘌呤(HYPX)水平以及与之相关的遗传特征与健康的自体输血受体,和接受异体输血的5816名重症患者的体外和体内溶血有关,这表明它们有可能做为改善输血效果的标志物。

据介绍,成熟的红细胞缺乏线粒体,因此在体内衰老或血库储存过程中只能依靠糖酵解产生三磷酸腺苷(ATP)。

附:英文原文

Title: Biological and genetic determinants of glycolysis: Phosphofructokinase isoforms boost energy status of stored red blood cells and transfusion outcomes

Author: Travis Nemkov, Daniel Stephenson, Eric J. Earley, Gregory R. Keele, Ariel Hay, Alicia Key, Zachary B. Haiman, Christopher Erickson, Monika Dzieciatkowska, Julie A. Reisz, Amy Moore, Mars Stone, Xutao Deng, Steven Kleinman, Steven L. Spitalnik, Eldad A. Hod, Krystalyn E. Hudson, Kirk C. Hansen, Bernhard O. Palsson, Gary A. Churchill, Nareg Roubinian, Philip J. Norris, Michael P. Busch, James C. Zimring, Grier P. Page, Angelo D’Alessandro

Issue&Volume: 2024-07-03

Abstract: Mature red blood cells (RBCs) lack mitochondria and thus exclusively rely on glycolysisto generate adenosine triphosphate (ATP) during aging in vivo or storage in blood banks. Here, we leveraged 13,029 volunteers from the RecipientEpidemiology and Donor Evaluation Study to identify associations between end-of-storagelevels of glycolytic metabolites and donor age, sex, and ancestry-specific geneticpolymorphisms in regions encoding phosphofructokinase 1, platelet (detected in matureRBCs); hexokinase 1 (HK1); and ADP-ribosyl cyclase 1 and 2 (CD38/BST1). Gene-metaboliteassociations were validated in fresh and stored RBCs from 525 Diversity Outbred miceand via multi-omics characterization of 1,929 samples from 643 human RBC units duringstorage. ATP and hypoxanthine (HYPX) levels—and the genetic traits linked to them—wereassociated with hemolysis in vitro and in vivo, both in healthy autologous transfusion recipients and in 5,816 critically ill patientsreceiving heterologous transfusions, suggesting their potential as markers to improvetransfusion outcomes.

DOI: 10.1016/j.cmet.2024.06.007

Source: https://www.cell.com/cell-metabolism/abstract/S1550-4131(24)00232-8

期刊信息

Cell Metabolism:《细胞—代谢》,创刊于2005年。隶属于细胞出版社,最新IF:31.373
官方网址:https://www.cell.com/cell-metabolism/home
投稿链接:https://www.editorialmanager.com/cell-metabolism/default.aspx