Ethylenediaminetetraacetic acid (EDTA) enhances cAMP production in human TDAG8-expressing cells

Ethylenediaminetetraacetic acid (EDTA) enhances cAMP production in human TDAG8-expressing cells
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乙二胺四乙酸 (EDTA) 增强人 TDAG8 表达细胞中 cAMP 的产生

DOI:
10.1016/j.bbrc.2022.07.110
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发表时间:
2022
影响因子:
3.1
通讯作者:
Tomura Hideaki
Tomura Hideaki
中科院分区:
生物学4区
文献类型:
--
作者:
Deai Masahito;Oya Rin;Saso Naosi;Tanaka Asahi;Uchida Izumi;Miyake Yuta;Tachihara Ryo;Otsugu Miku;Mine Ayumi;Sato Koichi;Tomura Hideaki

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乙二胺四乙酸(EDTA)是一种螯合剂,可与金属离子紧密结合。我们发现,cAMP反应元件(CRE)驱动的启动子活性的质子增强EDTA在人T细胞死亡相关基因8(TDAG 8)过表达的HEK 293 T细胞。EDTA的增强作用也被检测到质子诱导的cAMP的生产,位于上游的CRE驱动的启动子活性,即使在生理质子浓度pH 7.4。质子诱导的CRE驱动的启动子活性没有被其他螯合剂,乙二醇四乙酸(EGTA)和柠檬酸钠增强。增强的CRE-driven启动子活性EDTA没有衰减通过增加细胞外钙离子浓度。这些结果表明,EDTA增强作用可能不是由于其螯合作用,而是另一种EDTA特异性作用。在内源性表达TDAG 8和OGR 1(卵巢癌G蛋白偶联受体1)的人白血病细胞系HL-60中也检测到EDTA增强的cAMP产生,这表明EDTA的医学用途会影响造血细胞的生理和病理生理功能。
Ethylenediaminetetraacetic acid (EDTA) is a chelating agent that binds tightly to metal ions. We found that cAMP response element (CRE)-driven promoter activity by protons was enhanced by EDTA in human T-cell death-associated gene 8 (TDAG8)-overexpressed HEK293T cells. The enhancing action by EDTA was also detected by proton-induced cAMP production that is located upstream from the CRE-driven promoter activity even at physiological proton concentration pH7.4. The proton-induced CRE-driven promoter activity was not enhanced by other chelating agents, ethylene glycol tetraacetic acid (EGTA) and sodium citrate. The enhanced CRE-driven promoter activity by EDTA was not attenuated by increasing the extracellular calcium ion concentration. These results indicate that the EDTA-enhancing action may not be due to its chelating action but might rather be another EDTA-specific effect. Enhanced cAMP production by EDTA was also detected in a human leukemia cell line HL-60, in which TDAG8 and OGR1 (ovarian cancer G-protein-coupled receptor 1) were endogenously expressed, suggesting that the medical use of EDTA would influence the physiological and pathophysiological functions of hematopoietic cells.