Mitochondria-Targeted Antioxidant SkQ1 Improves Dermal Wound Healing in Genetically Diabetic Mice

被引：50

作者：

Demyanenko, Ilya A. ^{[1
]}

Zakharova, Vlada V. ^{[2
]}

Ilyinskaya, Olga P. ^{[1
]}

Vasilieva, Tamara V. ^{[1
]}

Fedorov, Artem V. ^{[1
]}

Manskikh, Vasily N. ^{[2
,3
]}

Zinovkin, Roman A. ^{[1
,2
,3
]}

Pletjushkina, Olga Yu ^{[2
]}

Chernyak, Boris V. ^{[2
]}

Skulachev, Vladimir P. ^{[2
,3
]}

Popova, Ekaterina N. ^{[2
]}

机构：

[1] Lomonosov Moscow State Univ, Fac Biol, Leninskie Gory 1-12, Moscow 119234, Russia

[2] Lomonosov Moscow State Univ, Belozersky Inst Physicochem Biol, Leninskie Gory 1-40, Moscow 119992, Russia

[3] Lomonosov Moscow State Univ, Inst Mitoengn, Leninskie Gory 1-73, Moscow 119992, Russia

来源：

OXIDATIVE MEDICINE AND CELLULAR LONGEVITY | 2017年 / 2017卷

基金：

俄罗斯科学基金会;

关键词：

OXIDATIVE STRESS; BETA; ACTIVATION; CELLS; COMPLICATIONS; HYPERGLYCEMIA; SENESCENCE; TISSUE;

D O I：

10.1155/2017/6408278

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Oxidative stress is widely recognized as an important factor in the delayed wound healing in diabetes. However, the role of mitochondrial reactive oxygen species in this process is unknown. It was assumed that mitochondrial reactive oxygen species are involved in many wound-healing processes in both diabetic humans and animals. We have applied the mitochondria-targeted antioxidant 10-(6'-plastoquinonyl) decyltriphenylphosphonium (SkQ1) to explore the role of mitochondrial reactive oxygen species in the wound healing of genetically diabetic mice. Healing of full-thickness excisional dermal wounds in diabetic C57BL/KsJ-db(-)/db(-) mice was significantly enhanced after long-term (12 weeks) administration of SkQ1. SkQ1 accelerated wound closure and stimulated epithelization, granulation tissue formation, and vascularization. On the 7th day after wounding, SkQ1 treatment increased the number of a-smooth muscle actin-positive cells (myofibroblasts), reduced the number of neutrophils, and increased macrophage infiltration. SkQ1 lowered lipid peroxidation level but did not change the level of the circulatory IL-6 and TNF. SkQ1 pretreatment also stimulated cell migration in a scratch-wound assay in vitro under hyperglycemic condition. Thus, a mitochondria-targeted antioxidant normalized both inflammatory and regenerative phases of wound healing in diabetic mice. Our results pointed to nearly all the major steps of wound healing as the target of excessive mitochondrial reactive oxygen species production in type II diabetes.

引用

页数：10

共 44 条

[31] Targeting of mitochondrial reactive oxygen species production does not avert lipid-induced insulin resistance in muscle tissue from mice [J].

Paglialunga, S. ;

van Bree, B. ;

Bosma, M. ;

Valdecantos, M. P. ;

Amengual-Cladera, E. ;

Jorgensen, J. A. ;

van Beurden, D. ;

den Hartog, G. J. M. ;

Ouwens, D. M. ;

Briede, J. J. ;

Schrauwen, P. ;

Hoeks, J. .

DIABETOLOGIA, 2012, 55 (10) :2759-2768

[32] Scavenging of Reactive Oxygen Species in Mitochondria Induces Myofibroblast Differentiation [J].

Popova, Ekaterina N. ;

Pletjushkina, Olga Y. ;

Dugina, Vera B. ;

Domnina, Lidia V. ;

Ivanova, Olga Y. ;

Izyumov, Denis S. ;

Skulachev, Vladimir P. ;

Chernyak, Boris V. .

ANTIOXIDANTS & REDOX SIGNALING, 2010, 13 (09) :1297-1307

[33] Chronic oxidative stress as a central mechanism for glucose toxicity in pancreatic islet beta cells in diabetes [J].

Robertson, RP .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (41) :42351-42354

[34]

S. Biosciences, 2008, PATHWAYS MAG

[35] Mitochondrial Hormesis and Diabetic Complications [J].

Sharma, Kumar .

DIABETES, 2015, 64 (03) :663-672

[36] Reactive oxygen species produced in mitochondria are involved in age-dependent changes of hematopoietic and mesenchymal progenitor cells in mice. A study with the novel mitochondria-targeted antioxidant SkQ1 [J].

Shipounova, I. N. ;

Svinareva, D. A. ;

Petrova, T. V. ;

Lyamzaev, K. G. ;

Chernyak, B. V. ;

Drize, N. I. ;

Skulachev, V. P. .

MECHANISMS OF AGEING AND DEVELOPMENT, 2010, 131 (06) :415-421

[37] The biology of chronic foot ulcers in persons with diabetes [J].

Sibbald, R. Gary ;

Woo, Kevin Y. .

DIABETES-METABOLISM RESEARCH AND REVIEWS, 2008, 24 :S25-S30

[38]

Skulachev MV, 2011, CURR DRUG TARGETS, V12, P800

[39] An attempt to prevent senescence: A mitochondrial approach [J].

Skulachev, Vladimir P. ;

Anisimov, Vladimir N. ;

Antonenko, Yuri N. ;

Bakeeva, Lora E. ;

Chernyak, Boris V. ;

Erichev, Valery P. ;

Filenko, Oleg F. ;

Kalinina, Natalya I. ;

Kapelko, Valery I. ;

Kolosova, Natalya G. ;

Kopnin, Boris P. ;

Korshunova, Galina A. ;

Lichinitser, Mikhail R. ;

Obukhova, Lidia A. ;

Pasyukova, Elena G. ;

Pisarenko, Oleg I. ;

Roginsky, Vitaly A. ;

Ruuge, Enno K. ;

Senin, Ivan I. ;

Severina, Inna I. ;

Skulachev, Maxim V. ;

Spivak, Irina M. ;

Tashlitsky, Vadim N. ;

Tkachuk, Vsevolod A. ;

Vyssokikh, Mikhail Yu. ;

Yaguzhinsky, Lev S. ;

Zorov, Dmitry B. .

BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS, 2009, 1787 (05) :437-461

[40] Differential Evaluation of Excisional Non-occluded Wound Healing in db/db Mice [J].

Tkalcevic, Vanesa Ivetic ;

Cuzic, Snjezana ;

Parnham, Michael J. ;

Pasalic, Ivanka ;

Brajsa, Karmen .

TOXICOLOGIC PATHOLOGY, 2009, 37 (02) :183-192

← 1 2 3 4 5 →