Please use this identifier to cite or link to this item: doi:10.22028/D291-39386
Title: The calcium channel modulator 2-APB hydrolyzes in physiological buffers and acts as an effective radical scavenger and inhibitor of the NADPH oxidase 2
Author(s): Slowik, Ewa Jasmin
Stankoska, Katerina
Bui, Nhat Nguyen
Pasieka, Bastian
Conrad, David
Zapp, Josef
Hoth, Markus
Bogeski, Ivan
Kappl, Reinhard
Language: English
Title: Redox Biology
Volume: 61
Publisher/Platform: Elsevier
Year of Publication: 2023
Free key words: 2-APB
Reactive oxygen species (ROS)
NOX inhibition
DDC notations: 500 Science
610 Medicine and health
Publikation type: Journal Article
Abstract: 2-aminoethoxydiphenyl borate (2-APB) is commonly used as a tool to modulate calcium signaling in physiological studies. 2-APB has a complex pharmacology and acts as activator or inhibitor of a variety of Ca2+ channels and transporters. While unspecific, 2-APB is one of the most-used agents to modulate store-operated calcium entry (SOCE) mediated by the STIM-gated Orai channels. Due to its boron core structure, 2-APB tends to readily hydrolyze in aqueous environment, a property that results in a complex physicochemical behavior. Here, we quantified the degree of hydrolysis in physiological conditions and identified the hydrolysis products diphenylborinic acid and 2-aminoethanol by NMR. Notably, we detected a high sensitivity of 2-APB/diphenylborinic acid towards decomposition by hydrogen peroxide to compounds such as phenylboronic acid, phenol, and boric acid, which were, in contrast to 2-APB itself and diphenylborinic acid, insufficient to affect SOCE in physiological experiments. Consequently, the efficacy of 2-APB as a Ca2+ signal modulator strongly depends on the reactive oxygen species (ROS) production within the experimental system. The antioxidant behavior of 2-APB towards ROS and its resulting decomposition are inversely correlated to its potency to modulate Ca2+ signaling as shown by electron spin resonance spectroscopy (ESR) and Ca2+ imaging. Finally, we observed a strong inhibitory effect of 2-APB, i.e., its hydrolysis product diphenylborinic acid, on NADPH oxidase (NOX2) activity in human monocytes. These new 2-APB properties are highly relevant for Ca2+ and redox signaling studies and for pharmacological application of 2-APB and related boron compounds.
DOI of the first publication: 10.1016/j.redox.2023.102654
URL of the first publication:
Link to this record: urn:nbn:de:bsz:291--ds-393867
ISSN: 2213-2317
Date of registration: 28-Mar-2023
Description of the related object: Supplementary data
Related object:
Faculty: M - Medizinische Fakultät
NT - Naturwissenschaftlich- Technische Fakultät
Department: M - Anästhesiologie
M - Biophysik
NT - Pharmazie
Professorship: M - Prof. Dr. Markus Hoth
M - Keiner Professur zugeordnet
NT - Prof. Dr. Alexandra K. Kiemer
Collections:SciDok - Der Wissenschaftsserver der Universität des Saarlandes

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