2. Academic Validation
  3. Ethylenediaminetetraacetic acid (EDTA) enhances cAMP production in human TDAG8-expressing cells

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

  • Biochem Biophys Res Commun. 2022 Oct 20:626:15-20. doi: 10.1016/j.bbrc.2022.07.110.
Masahito Deai 1,  Rin Oya 1,  Naosi Saso 1,  Asahi Tanaka 1,  Izumi Uchida 1,  Yuta Miyake 1,  Ryo Tachihara 1,  Miku Otsugu 1,  Ayumi Mine 1,  Koichi Sato 2,  Hideaki Tomura 3
Affiliations

Affiliations

  • 1 Laboratory of Cell Signaling Regulation, Department of Life Sciences, School of Agriculture, Meiji University, Kawasaki, 214-8571, Japan.
  • 2 Laboratory of Signal Transduction, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi, 371-8512, Japan.
  • 3 Laboratory of Cell Signaling Regulation, Department of Life Sciences, School of Agriculture, Meiji University, Kawasaki, 214-8571, Japan; Institute of Endocrinology, Meiji University, Kawasaki, 214-8571, Japan. Electronic address: tomurah@meiji.ac.jp.
PMID: 35964552 DOI: 10.1016/j.bbrc.2022.07.110
Abstract

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.

Keywords

Ethylenediaminetetraacetic acid (EDTA); HL-60; Human T-cell death-associated gene 8 (TDAG8); cAMP; cAMP response element (CRE)-Driven promoter activity.

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