Derivatives of Rhodamine 19 as Mild Mitochondria-targeted Cationic Uncouplers

被引：78

作者：

Antonenko, Yuri N. ^{[1
]}

Avetisyan, Armine V. ^{[1
]}

Cherepanov, Dmitry A. ^{[1
]}

Knorre, Dmitry A. ^{[1
]}

Korshunova, Galina A. ^{[1
]}

Markova, Olga V. ^{[1
]}

Ojovan, Silvia M. ^{[1
]}

Perevoshchikova, Irina V. ^{[1
]}

Pustovidko, Antonina V. ^{[1
]}

Rokitskaya, Tatyana I. ^{[1
]}

Severina, Inna I. ^{[1
]}

Simonyan, Ruben A. ^{[1
]}

Smirnova, Ekaterina A. ^{[1
]}

Sobko, Alexander A. ^{[1
]}

Sumbatyan, Natalia V. ^{[2
]}

Severin, Fedor F. ^{[1
]}

Skulachev, Vladimir P. ^{[1
,3
,4
]}

机构：

[1] Moscow MV Lomonosov State Univ, Belozersky Inst Physicochem Biol, Moscow 119991, Russia

[2] Moscow MV Lomonosov State Univ, Fac Chem, Moscow 119991, Russia

[3] Moscow MV Lomonosov State Univ, Fac Bioengn & Bioinformat, Moscow 119991, Russia

[4] Moscow MV Lomonosov State Univ, Inst Mitoengn, Moscow 119991, Russia

来源：

JOURNAL OF BIOLOGICAL CHEMISTRY | 2011年 / 286卷 / 20期

基金：

俄罗斯基础研究基金会;

关键词：

HYDROPHOBIC ION INTERACTIONS; LIPID BILAYER MEMBRANES; FATTY-ACIDS; PLASTOQUINONE DERIVATIVES; OXIDATIVE-PHOSPHORYLATION; SACCHAROMYCES-CEREVISIAE; LIPOPHILIC DICATIONS; INTERRUPT EXECUTION; YEAST; MECHANISM;

D O I：

10.1074/jbc.M110.212837

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

A limited decrease in mitochondrial membrane potential can be beneficial for cells, especially under some pathological conditions, suggesting that mild uncouplers (protonophores) causing such an effect are promising candidates for therapeutic uses. The great majority of protonophores are weak acids capable of permeating across membranes in their neutral and anionic forms. In the present study, protonophorous activity of a series of derivatives of cationic rhodamine 19, including dodecylrhodamine (C(12)R1) and its conjugate with plastoquinone (SkQR1), was revealed using a variety of assays. Derivatives of rhodamine B, lacking dissociable protons, showed no protonophorous properties. In planar bilayer lipid membranes, separating two compartments differing in pH, diffusion potential of H+ ions was generated in the presence of C(12)R1 and SkQR1. These compounds induced pH equilibration in liposomes loaded with the pH probe pyranine. C(12)R1 and SkQR1 partially stimulated respiration of rat liver mitochondria in State 4 and decreased their membrane potential. Also, C(12)R1 partially stimulated respiration of yeast cells but, unlike the anionic protonophore FCCP, did not suppress their growth. Loss of function of mitochondrial DNA in yeast (grande-petite transformation) is known to cause a major decrease in the mitochondrial membrane potential. We found that petite yeast cells are relatively more sensitive to the anionic uncouplers than to C(12)R1 compared with grande cells. Together, our data suggest that rhodamine 19-based cationic protonophores are self-limiting; their uncoupling activity is maximal at high membrane potential, but the activity decreases membrane potentials, which causes partial efflux of the uncouplers from mitochondria and, hence, prevents further membrane potential decrease.

引用

页码：17831 / 17840

页数：10

共 58 条

[1]

CARBOXYATRACTYLATE INHIBITS THE UNCOUPLING EFFECT OF FREE FATTY-ACIDS [J].

ANDREYEV, AY ;

BONDAREVA, TO ;

DEDUKHOVA, VI ;

MOKHOVA, EN ;

SKULACHEV, VP ;

VOLKOV, NI .

FEBS LETTERS, 1988, 226 (02) :265-269

[2]

THE ATP-ADP-ANTIPORTER IS INVOLVED IN THE UNCOUPLING EFFECT OF FATTY-ACIDS ON MITOCHONDRIA [J].

ANDREYEV, AY ;

BONDAREVA, TO ;

DEDUKHOVA, VI ;

MOKHOVA, EN ;

SKULACHEV, VP ;

TSOFINA, LM ;

VOLKOV, NI ;

VYGODINA, TV .

EUROPEAN JOURNAL OF BIOCHEMISTRY, 1989, 182 (03) :585-592

[3]

Mitochondria-targeted plastoquinone derivatives as tools to interrupt execution of the aging program. 1. Cationic plastoquinone derivatives: Synthesis and in vitro studies [J].

Antonenko, Y. N. ;

Avetisyan, A. V. ;

Bakeeva, L. E. ;

Chernyak, B. V. ;

Chertkov, V. A. ;

Domnina, L. V. ;

Ivanova, O. Yu. ;

Izyumov, D. S. ;

Khailova, L. S. ;

Klishin, S. S. ;

Korshunova, G. A. ;

Lyamzaev, K. G. ;

Muntyan, M. S. ;

Nepryakhina, O. K. ;

Pashkovskaya, A. A. ;

Pletjushkina, O. Yu. ;

Pustovidko, A. V. ;

Roginsky, V. A. ;

Rokitskaya, T. I. ;

Ruuge, E. K. ;

Saprunova, V. B. ;

Severina, I. I. ;

Simonyan, R. A. ;

Skulachev, I. V. ;

Skulachev, M. V. ;

Sumbatyan, N. V. ;

Sviryaeva, I. V. ;

Tashlitsky, V. N. ;

Vassiliev, J. M. ;

Vyssokikh, M. Yu. ;

Yaguzhinsky, L. S. ;

Zamyatnin, A. A., Jr. ;

Skulachev, V. P. .

BIOCHEMISTRY-MOSCOW, 2008, 73 (12) :1273-1287

[4]

pH determination by pyranine: Medium-related artifacts and their correction [J].

Avnir, Y ;

Barenholz, Y .

ANALYTICAL BIOCHEMISTRY, 2005, 347 (01) :34-41

[5]

Mitochondria-targeted plastoquinone derivatives as tools to interrupt execution of the aging program. 2. Treatment of some ROS- and Age-related diseases (heart arrhythmia, heart infarctions, kidney ischemia, and stroke) [J].

Bakeeva, L. E. ;

Barskov, I. V. ;

Egorov, M. V. ;

Isaev, N. K. ;

Kapelko, V. I. ;

Kazachenko, A. V. ;

Kirpatovsky, V. I. ;

Kozlovsky, S. V. ;

Lakomkin, V. L. ;

Levina, S. B. ;

Pisarenko, O. I. ;

Plotnikov, E. Y. ;

Saprunova, V. B. ;

Serebryakova, L. I. ;

Skulachev, M. V. ;

Stelmashook, E. V. ;

Studneva, I. M. ;

Tskitishvili, O. V. ;

Vasilyeva, A. K. ;

Victorov, I. V. ;

Zorov, D. B. ;

Skulachev, V. P. .

BIOCHEMISTRY-MOSCOW, 2008, 73 (12) :1288-1299

[6]

THE MISSING TERM IN EFFECTIVE PAIR POTENTIALS [J].

BERENDSEN, HJC ;

GRIGERA, JR ;

STRAATSMA, TP .

JOURNAL OF PHYSICAL CHEMISTRY, 1987, 91 (24) :6269-6271

[7]

Targeting dinitrophenol to mitochondria: Limitations to the development of a self-limiting mitochondrial protonophore [J].

Blaikie, Frances H. ;

Brown, Stephanie E. ;

Samuelsson, Linda M. ;

Brand, Martin D. ;

Smith, Robin A. J. ;

Murphy, Michael P. .

BIOSCIENCE REPORTS, 2006, 26 (03) :231-243

[8]

A HYDROXIDE ION CARRIER IN PLANAR PHOSPHOLIPID-BILAYER MEMBRANES - (C6F5)2HG (DIPENTAFLUOROPHENYLMERCURY) [J].

BLAUSTEIN, RO ;

FINKELSTEIN, A .

BIOCHIMICA ET BIOPHYSICA ACTA, 1988, 946 (02) :221-226

[9]

MECHANISM OF CONDUCTIVITY OF BIMOLECULAR LIPID-MEMBRANES IN PRESENCE OF TETRACHLOROTRIFLUOROMETHYLBENZIMIDAZOLE [J].

BORISOVA, MP ;

ERMISHKIN, LN ;

LIBERMAN, EA ;

SILBERSTEIN, AY ;

TROFIMOV, EM .

JOURNAL OF MEMBRANE BIOLOGY, 1974, 18 (3-4) :243-261

[10]

A mechanism for tamoxifen-mediated inhibition of acidification [J].

Chen, Y ;

Schindler, M ;

Simon, SM .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (26) :18364-18373

← 1 2 3 4 5 6 →