咨询与建议

看过本文的还看了

相关文献

该作者的其他文献

文献详情 >Apoptosis of leukemic cells ac... 收藏

Apoptosis of leukemic cells accompanies reduction in intracellular pH after targeted inhibition of the Na<SUP>+</SUP>/H<SUP>+</SUP> exchanger

白血病的房间的 Apoptosis 在 Na+/H+ exchanger 的指向的抑制以后在细胞内部的 pH 伴随减小

作     者:Rich, IN Worthington-White, D Garden, OA Musk, P 

作者机构:Palmetto Richland Mem Hosp S Columbia Canc Ctr Div Transplantat Med Columbia SC 29203 USA 

出 版 物:《BLOOD》 (血液)

年 卷 期:2000年第95卷第4期

页      面:1427-1434页

核心收录:

学科分类:1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 10[医学] 

主  题:阿米洛利/类似物和衍生物 阿米洛利/药理学 抗肿瘤药/药理学 细胞凋亡/药物作用 细胞凋亡/生理学 氢离子浓度 K562细胞 白血病/病理学 白血病/病理生理学 淋巴细胞/细胞学 淋巴细胞/药物作用 淋巴细胞/免疫学 小鼠 近交NOD 小鼠 SCID 钠氢反向转运物/拮抗剂和抑制剂 十四酰佛波乙酯/药理学 移植 异种 肿瘤细胞 培养的 成年人 动物 人类 小鼠 

摘      要:The Na+/H+ exchanger isoform 1 (NHE1) is primarily responsible for the regulation of intracellular pH (pH(i)), It is a ubiquitous, amiloride-sensitive, growth factor-activatable exchanger whose role has been implicated in cell-cycle regulation, apoptosis, and neoplasia, Here we demonstrate that leukemic cell lines and peripheral blood from primary patient leukemic samples exhibit a constitutively and statistically higher pH(i) than normal hematopoietic tissue, We then show that a direct correlation exists between pH(i) and cell-cycle status of normal hematopoietic and leukemic cells, Advantage was taken of this relationship by treating leukemic cells with the Na+/H+ exchanger inhibitor, 5-(N, N-hexamethylene) amiloride (HMA), which decreases the pH(i) and induces apoptosis, By incubating patient leukemic cells in vitro with pharmacologic doses of HMA for up to 5 hours, we show, using flow cytometry and fluorescent ratio imaging microscopy, that when the pH(i) decreases, apoptosis-measured by annexin-V and TUNEL methodologies-rapidly increases so that more than 90% of the leukemic cells are killed, The differential sensitivity exhibited between normal and leukemic cells allows consideration of NHE1 inhibitors as potential antileukemic agents. (C) 2000 by The American Society of Hematology.

读者评论 与其他读者分享你的观点

用户名:未登录
我的评分