Novel mitochondria-targeted antioxidants, "Skulachev-Ion" derivatives, accelerate dermal wound healing in animals

被引:26
作者
Demianenko, I. A. [2 ,3 ]
Vasilieva, T. V. [2 ,3 ]
Domnina, L. V. [1 ,3 ]
Dugina, V. B. [1 ,3 ]
Egorov, M. V. [3 ]
Ivanova, O. Y. [1 ,3 ]
Ilinskaya, O. P. [2 ,3 ]
Pletjushkina, O. Y. [1 ,3 ]
Popova, E. N. [1 ,3 ]
Sakharov, I. Y. [4 ]
Fedorov, A. V. [2 ,3 ]
Chernyak, B. V. [1 ,3 ]
机构
[1] Moscow MV Lomonosov State Univ, Belozersky Inst Physico Chem Biol, Moscow 119991, Russia
[2] Moscow MV Lomonosov State Univ, Fac Biol, Moscow 119991, Russia
[3] Moscow MV Lomonosov State Univ, Inst Mitoengn, Moscow 119991, Russia
[4] Moscow MV Lomonosov State Univ, Fac Chem, Moscow 119991, Russia
基金
俄罗斯基础研究基金会;
关键词
mitochondria-targeted antioxidants; SkQ1; myofibroblasts; inflammation; skin wounds; LIPID-PEROXIDATION PRODUCTS; NECROSIS-FACTOR-ALPHA; PLASTOQUINONE DERIVATIVES; INTERRUPT EXECUTION; ENDOTHELIAL-CELLS; HYDROGEN-PEROXIDE; OXIDATIVE STRESS; CHEMOTACTIC ACTIVITY; ADHESION MOLECULE-1; N-ACETYLCYSTEINE;
D O I
10.1134/S000629791003003X
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
It is shown that the novel mitochondria-targeted antioxidant SkQ1, (10-(6'-plastoquinonyl) decyltriphenylphosphonium) stimulates healing of full-thickness dermal wounds in mice and rats. Treatment with nanomolar doses of SkQ1 in various formulations accelerated wound cleaning and suppressed neutrophil infiltration at the early (7 h) steps of inflammatory phase. SkQ1 stimulated formation of granulation tissue and increased the content of myofibroblasts in the beginning of regenerative phase of wound healing. Later this effect caused accumulation of collagen fibers. Local treatment with SkQ1 stimulated re-epithelization of the wound. Lifelong treatment of mice with SkQ1 supplemented with drinking water strongly stimulated skin wounds healing in old (28 months) animals. In an in vitro model of wound in human cell cultures, SkQ1 stimulated movement of epitheliocytes and fibroblasts into the "wound". Myofibroblast differentiation of subcutaneous fibroblasts was stimulated by SkQ1. It is suggested that SkQ1 stimulates wound healing by suppression of the negative effects of oxidative stress in the wound and also by induction of differentiation. Restoration of regenerative processes in old animals is consistent with the "rejuvenation" effects of SkQ1, which prevents some gerontological diseases.
引用
收藏
页码:274 / 280
页数:7
相关论文
共 40 条
  • [1] 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
    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.
    [J]. BIOCHEMISTRY-MOSCOW, 2008, 73 (12) : 1300 - 1316
  • [2] Mitochondria-targeted plastoquinone derivatives as tools to interrupt execution of the aging program. 5. SkQ1 prolongs lifespan and prevents development of traits of senescence
    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.
    [J]. BIOCHEMISTRY-MOSCOW, 2008, 73 (12) : 1329 - 1342
  • [3] Protective effects of mitochondria-targeted antioxidant SkQ in aqueous and lipid membrane environments
    Antonenko, Y. N.
    Roginsky, V. A.
    Pashkovskaya, A. A.
    Rokitskaya, T. I.
    Kotova, E. A.
    Zaspa, A. A.
    Chernyak, B. V.
    Skulachev, V. P.
    [J]. JOURNAL OF MEMBRANE BIOLOGY, 2008, 222 (03) : 141 - 149
  • [4] Mitochondria-targeted plastoquinone derivatives as tools to interrupt execution of the aging program. 1. Cationic plastoquinone derivatives: Synthesis and in vitro studies
    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.
    [J]. BIOCHEMISTRY-MOSCOW, 2008, 73 (12) : 1273 - 1287
  • [5] The NADPH oxidase of endothelial cells
    Babior, BM
    [J]. IUBMB LIFE, 2000, 50 (4-5) : 267 - 269
  • [6] Phagocytes and oxidative stress
    Babior, BM
    [J]. AMERICAN JOURNAL OF MEDICINE, 2000, 109 (01) : 33 - 44
  • [7] 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)
    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.
    [J]. BIOCHEMISTRY-MOSCOW, 2008, 73 (12) : 1288 - 1299
  • [8] Production of reactive oxygen species in mitochondria of HeLa cells under oxidative stress
    Chernyak, Boris V.
    Izyumov, Denis S.
    Lyamzaev, Konstantin G.
    Pashkovskaya, Alina A.
    Pletjushkina, Olga Y.
    Antonenko, Yuri N.
    Sakharov, Dmitrii V.
    Wirtz, Karel W. A.
    Skulachev, Vladimir P.
    [J]. BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS, 2006, 1757 (5-6): : 525 - 534
  • [9] INTERACTION BETWEEN NEUTROPHILS AND 4-HYDROXYALKENALS AND CONSEQUENCES ON NEUTROPHIL MOTILITY
    CURZIO, M
    [J]. FREE RADICAL RESEARCH COMMUNICATIONS, 1988, 5 (02): : 55 - 66
  • [10] CURZIO M, 1987, INT J TISSUE REACT, V9, P295