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A short-chain alkyl derivative of Rhodamine 19 acts as a mild uncoupler of mitochondria and a neuroprotectorстатья
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: 2 ноября 2014 г.
- Авторы: Khailova LS, Silachev DN, Rokitskaya TI, Avetisyan AV, Lyamzaev KG, Severina II, Il'yasova TM, Gulyaev MV, Dedukhova VI, Trendeleva TA, Plotnikov EY, Zvyagilskaya RA, Chernyak BV, Zorov DB, Antonenko YN, Skulachev VP
- Журнал: Biochimica et Biophysica Acta - Bioenergetics
- Том: 1837
- Номер: 10
- Год издания: 2014
- Издательство: Elsevier BV
- Местоположение издательства: Netherlands
- Первая страница: 1739
- Последняя страница: 1747
- DOI: 10.1016/j.bbabio.2014.07.006
- Аннотация: Limited uncoupling of oxidative phosphorylation is known to be beneficial in various laboratory models of diseases. The search for cationic uncouplers is promising as their protonophorous effect is self-limiting because these uncouplers lower membrane potential which is the driving force for their accumulation in mitochondria. In this work, the penetrating cation Rhodamine 19 butyl ester (C4R1) was found to decrease membrane potential and to stimulate respiration of mitochondria, appearing to be a stronger uncoupler than its more hydrophobic analog Rhodamine 19 dodecyl ester (C12R1). Surprisingly, C12R1 increased H+ conductance of artificial bilayer lipid membranes or induced mitochondria swelling in potassium acetate with valinomycin at concentrations lower than C4R1. This paradox might be explained by involvement of mitochondrial proteins in the uncoupling action of C4R1. In experiments with HeLa cells, C4R1 rapidly and selectively accumulated in mitochondria and stimulated oligomycin-sensitive respiration as a mild uncoupler. C4R1 was effective in preventing oxidative stress induced by brain ischemia and reperfusion in rats: it suppressed stroke-induced brain swelling and prevented the decline in neurological status more effectively than C12R1. Thus, C4R1 seems to be a promising example of a mild uncoupler efficient in treatment of brain pathologies related to oxidative stress.
- Добавил в систему: Антоненко Юрий Николаевич