| Autor: |
Fedor F. Severin, Tatyana I. Rokitskaya, Yuri N. Antonenko, Inna I. Severina, Vladimir P. Skulachev, Antonina V. Pustovidko, Alexander A. Sobko |
| Rok vydání: |
2011 |
| Předmět: |
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| Zdroj: |
Biophysical Journal. 100(3) |
| ISSN: |
0006-3495 |
| DOI: |
10.1016/j.bpj.2010.12.2694 |
| Popis: |
Mild uncoupling of mitochondria assumes that partial decrease in membrane potential is beneficial for cells especially under some pathological conditions, suggesting that uncouplers are good candidates for therapeutic uses. The majority of known protonophoric uncouplers are weak acids capable to permeate across membranes in neutral and anionic forms. In the present study, protonophoric activity of a series of derivatives of cationic rhodamine 19 (including dodecylrhodamine C12R1 and its conjugate with plastoquinone SkQR1) but not of similar derivatives of rhodamine B was revealed by using a variety of assays. In planar bilayer lipid membranes, diffusion potential of hydrogen ions was formed in the presence of C12R1 and SkQR1. These compounds induced pH equilibration in liposomes loaded with the pH probe pyranine similarly to the well-known uncoupler FCCP. C12R1 and SkQR1 also stimulated respiration of rat liver mitochondria and decreased their membrane potential as measured by DiS-C3-5. The protonophoric activity of alkylrhodamines strongly depended on the number of carbon atoms in their alkyl chain (n): it was maximal at n about 10-12 and substantially decreased at n = 16. We surmise that the proton transport involves translocation of neutral and protonated cationic forms of C12R1 across a membrane. Based on the fact that SkQR1 accumulates in mitochondria of mammalian cells and protects them from oxidative stress (Bakeeva et al. 2008, Biochemistry Moscow, 73:1288-1299), it can be proposed that the protonophore-induced uncoupling could be involved in the protective effect of SkQR1 along with the direct antioxidant effect of plastoquinone. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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