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)

被引：142

作者：

Bakeeva, L. E. ^{[1
]}

Barskov, I. V. ^{[2
]}

Egorov, M. V. ^{[3
]}

Isaev, N. K. ^{[1
,2
]}

Kapelko, V. I. ^{[4
]}

Kazachenko, A. V. ^{[6
]}

Kirpatovsky, V. I. ^{[6
]}

Kozlovsky, S. V. ^{[3
]}

Lakomkin, V. L. ^{[4
]}

Levina, S. B. ^{[2
]}

Pisarenko, O. I. ^{[4
]}

Plotnikov, E. Y. ^{[1
]}

Saprunova, V. B. ^{[1
]}

Serebryakova, L. I. ^{[4
]}

Skulachev, M. V. ^{[3
]}

Stelmashook, E. V. ^{[2
]}

Studneva, I. M. ^{[4
]}

Tskitishvili, O. V. ^{[4
]}

Vasilyeva, A. K. ^{[1
]}

Victorov, I. V. ^{[5
]}

Zorov, D. B. ^{[1
]}

Skulachev, V. P. ^{[1
,3
,7
]}

机构：

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

[2] Russian Acad Med Sci, Inst Neurol, Dept Brain Res, Moscow 105064, Russia

[3] Moscow MV Lomonosov State Univ, Ctr Mitoengn, Moscow 119991, Russia

[4] Cardiol Res Ctr, Inst Expt Cardiol, Moscow 121552, Russia

[5] Serbsky State Res Ctr Social & Forens Psychiat, Moscow 119992, Russia

[6] Inst Urol, Moscow 105425, Russia

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

来源：

BIOCHEMISTRY-MOSCOW | 2008年 / 73卷 / 12期

基金：

俄罗斯基础研究基金会;

关键词：

mitochondria-targeted antioxidant; plastoquinone; arrhythmia; heart; kidney; infarction; stroke;

D O I：

10.1134/S000629790812002X

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Effects of 10-(6'-plastoquinonyl) decyltriphenylphosphonium (SkQ1) and 10-(6'-plastoquinonyl) decylrhod-amine 19 (SkQR1) on rat models of H2O2- and ischemia-induced heart arrhythmia, heart infarction, kidney ischemia, and stroke have been studied ex vivo and in vivo. In all the models listed, SkQ1 and/or SkQR1 showed pronounced protective effect. Supplementation of food with extremely low SkQ1 amount (down to 0.02 nmol SkQ1/kg per day for 3 weeks) was found to abolish the steady heart arrhythmia caused by perfusion of isolated rat heart with H2O2 or by ischemia/reperfusion. Higher SkQ1 (125-250 nmol/kg per day for 2-3 weeks) was found to decrease the heart infarction region induced by an in vivo ischemia/reperfusion and lowered the blood levels of lactate dehydrogenase and creatine kinase increasing as a result of ischemia/reperfusion. In single-kidney rats, ischemia/reperfusion of the kidney was shown to kill the majority of the animals in 2-4 days, whereas one injection of SkQ1 or SkQR1 (1 mu mol/kg a day before ischemia) saved lives of almost all treated rats. Effect of SkQR1 was accompanied by decrease in ROS (reactive oxygen species) level in kidney cells as well as by partial or complete normalization of blood creatinine and of some other kidney-controlled parameters. On the other hand, this amount of SkQ1 (a SkQ derivative of lower membrane-penetrating ability than SkQR1) saved the life but failed to normalize ROS and creatinine levels. Such an effect indicates that death under conditions of partial kidney dysfunction is mediated by an organ of vital importance other than kidney, the organ in question being an SkQ1 target. In a model of compression brain ischemia/reperfusion, a single intraperitoneal injection of SkQR1 to a rat (1 mu mol/kg a day before operation) effectively decreased the damaged brain area. SkQ1 was ineffective, most probably due to lower permeability of the blood-brain barrier to this compound.

引用

页码：1288 / 1299

页数：12

共 28 条

[1] Targeting an antioxidant to mitochondria decreases cardiac ischemia-reperfusion injury [J].

Adlam, VJ ;

Harrison, JC ;

Porteous, CM ;

James, AM ;

Smith, RAJ ;

Murphy, MP ;

Sammut, IA .

FASEB JOURNAL, 2005, 19 (09) :1088-1095

[2] Mitochondria-targeted plastoquinone derivatives as tools to interrupt execution of the aging program. 3. Inhibitory effect of SkQ1 on tumor development from p53-deficient cells [J].

Agapova, L. S. ;

Chernyak, B. V. ;

Domnina, L. V. ;

Dugina, V. B. ;

Efimenko, A. Yu. ;

Fetisova, E. K. ;

Ivanova, O. Yu. ;

Kalinina, N. I. ;

Khromova, N. V. ;

Kopnin, B. P. ;

Kopnin, P. B. ;

Korotetskaya, M. V. ;

Lichinitser, M. R. ;

Lukashev, A. L. ;

Pletjushkina, O. Yu. ;

Popova, E. N. ;

Skulachev, M. V. ;

Shagieva, G. S. ;

Stepanova, E. V. ;

Titova, E. V. ;

Tkachuk, V. A. ;

Vasiliev, J. M. ;

Skulachev, V. P. .

BIOCHEMISTRY-MOSCOW, 2008, 73 (12) :1300-1316

[3] Temporal profile of ultrastructural changes in cortical neurons after a compression lesion [J].

Andersson, B. ;

Bjelke, B. ;

Sykova, E. .

PHYSIOLOGICAL RESEARCH, 2006, 55 (03) :339-348

[4] Temporal profile of ultrastructural changes in cortical neurons after a photochemical lesion [J].

Andersson, B ;

Wu, XC ;

Bjelke, B ;

Syková, E .

JOURNAL OF NEUROSCIENCE RESEARCH, 2004, 77 (06) :901-912

[5]

ANDREWS R J, 1992, Neurological Research, V14, P12

[6] Mitochondria-targeted plastoquinone derivatives as tools to interrupt execution of the aging program. 5. SkQ1 prolongs lifespan and prevents development of traits of senescence [J].

Anisimov, V. N. ;

Bakeeva, L. E. ;

Egormin, P. A. ;

Filenko, O. F. ;

Isakova, E. F. ;

Manskikh, V. N. ;

Mikhelson, V. M. ;

Panteleeva, A. A. ;

Pasyukova, E. G. ;

Pilipenko, D. I. ;

Piskunova, T. S. ;

Popovich, I. G. ;

Roshchina, N. V. ;

Rybina, O. Yu. ;

Saprunova, V. B. ;

Samoylova, T. A. ;

Semenchenko, A. V. ;

Skulachev, M. V. ;

Spivak, I. M. ;

Tsybul'ko, E. A. ;

Tyndyk, M. L. ;

Vyssokikh, M. Yu. ;

Yurova, M. N. ;

Zabezhinsky, M. A. ;

Skulachev, V. P. .

BIOCHEMISTRY-MOSCOW, 2008, 73 (12) :1329-1342

[7] 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

[8] INVOLVEMENT OF REACTIVE OXYGEN SPECIES IN KIDNEY DAMAGE [J].

BAUD, L ;

ARDAILLOU, R .

BRITISH MEDICAL BULLETIN, 1993, 49 (03) :621-629

[9] Mitochondrial production of oxidants is necessary for physiological calcium oscillations [J].

Camello-Almaraz, MC ;

Pozo, MJ ;

Murphy, MP ;

Camello, PJ .

JOURNAL OF CELLULAR PHYSIOLOGY, 2006, 206 (02) :487-494

[10] EXCITATION-CONTRACTION COUPLING IN SINGLE GUINEA-PIG VENTRICULAR MYOCYTES EXPOSED TO HYDROGEN-PEROXIDE [J].

GOLDHABER, JI ;

LIU, E .

JOURNAL OF PHYSIOLOGY-LONDON, 1994, 477 (01) :135-147

← 1 2 3 →