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

• Published in: Biochemical and biophysical research communications 2022-10, Vol.626, p.15-20
• Main Authors: Deai, Masahito, Oya, Rin, Saso, Naosi, Tanaka, Asahi, Uchida, Izumi, Miyake, Yuta, Tachihara, Ryo, Otsugu, Miku, Mine, Ayumi, Sato, Koichi, Tomura, Hideaki
• Format: Article
• Language: English
• Subjects: cAMP; cAMP response element (CRE)-Driven promoter activity; Ethylenediaminetetraacetic acid (EDTA); HL-60; Human T-cell death-associated gene 8 (TDAG8)
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2022.07.110

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. •EDTA enhanced cAMP production by protons in human TDAG8-overexpressed cells.•EGTA and sodium citrate did not enhance the cAMP production.•EDTA enhanced cAMP production in HL-60 cells.