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
  • 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: [email protected].
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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