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Mitochondria-targeted 1,4-naphthoquinone (SkQN) is a powerful prooxidant and cytotoxic agentстатья Исследовательская статья
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: 7 июля 2020 г.
- Авторы: Goleva Tatyana N., Lyamzaev Konstantin G., Rogov Anton G., Khailova Ljudmila S., Epremyan Khoren K., Shumakovich Galina P., Domnina Lidia V., Ivanova Olga Yu, Marmiy Natalia V., Zinevich Tatiana V., Esipov Dmitry S., Zvyagilskaya Renata A., Skulachev Vladimir P., Chernyak Boris V.
- Журнал: Biochimica et Biophysica Acta - Bioenergetics
- Том: 1861
- Номер: 8
- Год издания: 2020
- Издательство: Elsevier BV
- Местоположение издательства: Netherlands
- Первая страница: 148210
- DOI: 10.1016/j.bbabio.2020.148210
- Аннотация: An increase in the production of reactive oxygen species (ROS) in mitochondria due to targeted delivery of redox active compounds may be useful in studies of modulation of cell functions by mitochondrial ROS. Recently, the mitochondria-targeted derivative of menadione (MitoK3) was synthesized. However, MitoK3 did not induce mitochondrial ROS production and lipid peroxidation while exerting significant cytotoxic action. Here we synthesized 1,4-naphthoquinone conjugated with alkyltriphenylphosphonium (SkQN) as a prototype of mitochondria-targeted prooxidant, and its redox properties, interactions with isolated mitochondria, yeast cells and various human cell lines were investigated. According to electrochemical measurements, SkQN was more active redox agent and, due to the absence of methyl group in the naphthoquinone ring, more reactive as electrophile than MitoK3. SkQN (but not MitoK3) stimulated hydrogen peroxide production in isolated mitochondria. At low concentrations, SkQN stimulated state 4 respiration in mitochondria, decreased membrane potential, and blocked ATP synthesis, being more efficient uncoupler of oxidative phosphorylation than MitoK3. In yeast cells, SkQN decreased cell viability and induced oxidative stress and mitochondrial fragmentation. SkQN killed various tumor cells much more efficiently than MitoK3. Since many tumors are characterized by increased oxidative stress, the use of new mitochondria-targeted prooxidants may be a promising strategy for anticancer therapy.
- Добавил в систему: Лямзаев Константин Геннадьевич