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Mechanism of action of an old antibiotic revisited: Role of calcium ions in protonophoric activity of usnic acidстатья
Статья опубликована в высокорейтинговом журнале
Информация о цитировании статьи получена из
Web of Science,
Scopus
Статья опубликована в журнале из списка Web of Science и/или Scopus
Дата последнего поиска статьи во внешних источниках: 25 апреля 2019 г.
- Авторы: Antonenko Yuri N., Khailova Ljudmila S., Rokitskaya Tatyana I., Nosikova Ekaterina S., Nazarov Pavel A., Luzina O., Salakhutdinov Nariman F., Kotova Elena A.
- Журнал: Biochimica et Biophysica Acta - Bioenergetics
- Том: 1860
- Номер: 4
- Год издания: 2019
- Издательство: Elsevier BV
- Местоположение издательства: Netherlands
- Первая страница: 310
- Последняя страница: 316
- DOI: 10.1016/j.bbabio.2019.01.005
- Аннотация: 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.
- Добавил в систему: Антоненко Юрий Николаевич