Usnic acid as calcium ionophore and mast cells stimulator

• Published in: Biochimica et biophysica acta. Biomembranes Vol. 1862; no. 9; p. 183303
• Main Authors: Chelombitko, Maria A., Firsov, Alexander M., Kotova, Elena A., Rokitskaya, Tatyana I., Khailova, Ljudmila S., Popova, Lyudmila B., Chernyak, Boris V., Antonenko, Yuri N.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.09.2020
• Subjects: 2,4-Dinitrophenol - chemistry; Animals; Benzofurans - chemistry; Benzofurans - pharmacology; Calcimycin - pharmacology; Calcium ionophore; Calcium Ionophores - chemistry; Calcium Ionophores - pharmacology; Cell Line, Tumor; Erythrocytes - drug effects; Humans; Ion Transport - drug effects; Lichens - chemistry; Mast cells; Membrane potential; Mitochondria - drug effects; Mitochondrial uncoupler; Oxidative Phosphorylation - drug effects; Protonophore; Protons; Rats; Usnic acid; RR; CCCP; Usnic acid; DNP; Mitochondrial uncoupler; Mast cells; Protonophore; Membrane potential; UA; Calcium ionophore; RBL-2H3; BAPTA-AM
• ISSN: 0005-2736; 1879-2642
• DOI: 10.1016/j.bbamem.2020.183303

Usnic acid (UA), a secondary lichen metabolite, has long been popular as one of natural fat-burning dietary supplements. Similar to 2,4-dinitrophenol, the weight-loss effect of UA is assumed to be associated with its protonophoric uncoupling activity. Recently, we have shown that the ability of UA to shuttle protons across both mitochondrial and artificial membranes is strongly modulated by the presence of calcium ions in the medium. Here, by using fluorescent probes, we studied the calcium-transporting capacity of usnic acid in a variety of membrane systems comprising liposomes, isolated rat liver mitochondria, erythrocytes and rat basophilic leukemia cell culture (RBL-2H3). At concentrations of tens of micromoles, UA appeared to be able to carry calcium ions across membranes in all the systems studied. Similar to the calcium ionophore A23187, UA caused degranulation of RBL-2H3 cells. Therefore, UA, being a protonophoric uncoupler of oxidative phosphorylation, at higher concentrations manifests itself as a calcium ionophore, which could be relevant to its overdose toxicity in humans and also its phytotoxicity. [Display omitted] •Usnic acid (UA) induced efflux of Ca2+ but not that of Zn2+ from liposomes•UA (10 μM) exhibited Ca2+ transport activity in isolated rat liver mitochondria•UA induced elevation of cytosolic Ca2+ in the RBL-2H3 cell line, a mast cell analogue•UA caused degranulation of RBL-2H3 cells similar to the Ca2+ ionophore A23187