Exploiting endobiotic metabolic pathways to target xenobiotic antioxidants to mitochondria

被引：3

作者：

Anders, M. W. ^{[1
]}

机构：

[1] Univ Rochester, Med Ctr, Dept Physiol & Pharmacol, Rochester, NY 14642 USA

来源：

MITOCHONDRION | 2013年 / 13卷 / 05期

关键词：

Mitochondria; Antioxidants; Drug targeting; beta-oxidation; Prodrugs; ACYL-COA DEHYDROGENASE; S-(1,2 DICHLOROVINYL)-3-MERCAPTOPROPIONIC ACID; OXIDATION-DEPENDENT BIOACTIVATION; PERMEABLE PEPTIDE ANTIOXIDANTS; ISCHEMIA-REPERFUSION INJURY; PLASTOQUINONE DERIVATIVES; INTERRUPT EXECUTION; BETA-OXIDATION; NEURODEGENERATIVE DISEASES; PENETRATING PEPTIDES;

D O I：

10.1016/j.mito.2012.10.015

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Oxidative stress plays a role in a range of human disease entities. Hence, strategies to target antioxidants to mitochondria are an active area of investigation. Triphenylphosphonium cation-based antioxidants and SS-peptides have been described and show significant uptake by mitochondria and effectiveness in animal models of conditions linked to oxidative stress. We tested the hypothesis that the mitochondrial beta-oxidation pathway could be exploited to activate the antioxidant phenolic and methimazole prodrugs. Most compounds studied underwent mitochondrial biotransformation to release their antioxidant moieties, and some were cytoprotective in a hypoxia-reoxygenation model in rat cardiomyocytes. These results demonstrate the feasibility of exploiting mitochondrial bioactivation reactions for targeted drug delivery. (C) 2012 Elsevier B.V. and Mitochondria Research Society. All rights reserved.

引用

页码：454 / 463

页数：10

共 111 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] Mitochondria: new drug targets for oxidative stress-induced diseases [J].

Anders, M. W. ;

Robotham, James L. ;

Sheu, Shey-Shing .

EXPERT OPINION ON DRUG METABOLISM & TOXICOLOGY, 2006, 2 (01) :71-79

[4] Glutathione-dependent bioactivation of haloalkenes [J].

Anders, MW ;

Dekant, W .

ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY, 1998, 38 :501-537

[5] 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

[6]

[Anonymous], 1904, Beitr Chem Physiol Pathol

[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] Efficient reduction of lipoamide and lipoic acid by mammalian thioredoxin reductase [J].

Arner, ESJ ;

Nordberg, J ;

Holmgren, A .

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1996, 225 (01) :268-274

[9] Differential expression of TRPM2 and TRPV4 channels and their potential role in oxidative stress-induced cell death in organotypic hippocampal culture [J].

Bai, Ji-Zhong ;

Lipski, Janusz .

NEUROTOXICOLOGY, 2010, 31 (02) :204-214

[10] METABOLIC-ACTIVATION OF VALPROIC ACID AND DRUG-MEDIATED HEPATOTOXICITY - ROLE OF THE TERMINAL OLEFIN, 2-NORMAL-PROPYL-4-PENTENOIC ACID [J].

BAILLIE, TA .

CHEMICAL RESEARCH IN TOXICOLOGY, 1988, 1 (04) :195-199

← 1 2 3 4 5 6 7 8 9 10 →