Mechanism of action of an old antibiotic revisited: Role of calcium ions in protonophoric activity of usnic acid

Mechanism of action of an old antibiotic revisited: Role of calcium ions in protonophoric activity of usnic acid Full article

Journal

Biochimica et Biophysica Acta - Bioenergetics
ISSN: 0005-2728 , E-ISSN: 0006-3002

Output data

Year: 2019, Volume: 1860, Number: 4, Pages: 310-316 Pages count : 7 DOI: 10.1016/j.bbabio.2019.01.005

Tags

Usnic acid; Bilayer lipid membrane; Mitochondrial uncoupler; Protonophore; Membrane potential; Calcium chelator

Authors

Antonenko Yuri N. ¹ , Khailova Ljudmila S. ¹ , Rokitskaya Tatyana I. ¹ , Nosikova Ekaterina S. ² , Nazarov Pavel A. ¹ , Luzina Ol'ga A. ³ , Salakhutdinov Nariman F. ³ , Kotova Elena A. ¹

Affiliations

1	(Данные Web of science) Lomonosov Moscow State Univ, Belozersky Inst Physicochem Biol, Moscow 119991, Russia
2	(Данные Web of science) Lomonosov Moscow State Univ, Dept Bioengn & Bioinformat, Moscow 119991, Russia
3	(Данные Web of science) Russian Acad Sci, Novosibirsk Organ Chem Inst, Siberian Branch, Novosibirsk 630090, Russia

Usnic acid (UA), an old antibiotic and one of the first described mitochondrial uncouplers, has demonstrated many beneficial activities, such as antimicrobial, antiviral, antitumour and anti-inflammatory properties. Here, we performed a thorough investigation of effects of usnic acid and its analogues on artificial planar bilayer lipid membrane (BLM), rat liver mitochondria and bacteria. Surprisingly enough, all of the three hydroxyl groups of UA appeared to be involved in its proton-shuttling activity on BLM. We ascribed this fact to an ability of UA to form complexes with calcium ions, aiding it in cycling protons across the membrane. Actually, the addition of calcium ions markedly stimulated the UA-induced electrical current across BLM. By using the calcium ionophore A23187, we proved the involvement of calcium ions in the UA uncoupling action on isolated rat liver mitochondria. The calcium-chelating property of UA was demonstrated here by the method of extracting metal ions into a hydrophobic phase. Modification of any of the hydroxyl groups in UA dramatically reduced not only the UA-induced current across BLM and the UA-mediated calcium extraction, but also the uncoupling activity of UA in mitochondria and the inhibiting effect of UA on the growth of Bacillus subtilis. The ability of UA to cause dissipation of membrane potential in isolated liver mitochondria and bacterial cells was shown here for the first time. In view of the data obtained, the protonophoric activity of UA is considered to make a significant contribution to its antibacterial action.

Antonenko Y.N. , Khailova L.S. , Rokitskaya T.I. , Nosikova E.S. , Nazarov P.A. , Luzina O.A. , Salakhutdinov N.F. , Kotova E.A.
Mechanism of action of an old antibiotic revisited: Role of calcium ions in protonophoric activity of usnic acid

Biochimica et Biophysica Acta - Bioenergetics. 2019. V.1860. N4. P.310-316. DOI: 10.1016/j.bbabio.2019.01.005 WOS Scopus РИНЦ

Full text from publisher

Published print:

Apr 1, 2019

Web of science	WOS:000461530000004
Scopus	2-s2.0-85060926878
Elibrary	41789436
OpenAlex	W2914101256