Effects of alkyl side chain modification of coenzyme Q10 on mitochondrial respiratory chain function and cytoprotection

被引：19
作者：
Fash, David M. [1 ,2 ]
Khdour, Omar M. [1 ,2 ]
Sahdeo, Sunil J. [3 ]
Goldschmidt, Ruth [1 ,2 ]
Jaruvangsanti, Jennifer [1 ,2 ]
Dey, Sriloy [1 ,2 ]
Arce, Pablo M. [1 ,2 ]
Collin, Valerie C. [1 ,2 ]
Cortopassi, Gino A. [3 ]
Hecht, Sidney M. [1 ,2 ]
机构：
[1] Arizona State Univ, Ctr BioEnerget, Biodesign Inst, Tempe, AZ 85287 USA
[2] Arizona State Univ, Dept Chem & Biochem, Tempe, AZ 85287 USA
[3] Univ Calif Davis, Dept Mol Biosci, Davis, CA 95616 USA
来源：
BIOORGANIC & MEDICINAL CHEMISTRY | 2013年 / 21卷 / 08期
关键词：
Coenzyme Q(10); Electron transport chain; Oxygen consumption; Reactive oxygen species; Cytoprotection; OXIDATIVE STRESS; REACTIVE OXYGEN; ANTIOXIDANT; DYSFUNCTION; UBIQUINONE; CORRELATE; ANALOGS; CELLS;
D O I：
10.1016/j.bmc.2013.01.075
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：
The effect of the alkyl side chain length of coenzyme Q(10) on mitochondrial respiratory chain function has been investigated by the use of synthetic ubiquinone derivatives. Three analogues (3, 4 and 6) were identified that exhibited significantly improved effects on mitochondrial oxygen consumption and mitochondrial membrane potential, and also conferred significant cytoprotection on cultured mammalian cells in which glutathione had been depleted by treatment with diethyl maleate. The analogues also exhibited lesser inhibition of the electron transport chain than idebenone. The results obtained provide guidance for the design of CoQ(10) analogues with improved activity compared to that of idebenone (1), the latter of which is undergoing evaluation in the clinic as a therapeutic agent. (C) 2013 Elsevier Ltd. All rights reserved.
引用
收藏
页码：2346 / 2354
页数：9
相关论文
共 42 条
[1]   Analysis of the structural and mechanistic factors in antioxidants that preserve mitochondrial function and confer cytoprotection [J].
Arce, Pablo M. ;
Goldschmidt, Ruth ;
Khdour, Omar M. ;
Madathil, Manikandadas M. ;
Jaruvangsanti, Jennifer ;
Dey, Sriloy ;
Fash, David M. ;
Armstrong, Jeffrey S. ;
Hecht, Sidney M. .
BIOORGANIC & MEDICINAL CHEMISTRY, 2012, 20 (17) :5188-5201
[2]   A Strategy for Suppressing Redox Stress within Mitochondria [J].
Arce, Pablo M. ;
Khdour, Omar M. ;
Goldschmidt, Ruth ;
Armstrong, Jeffrey S. ;
Hecht, Sidney M. .
ACS MEDICINAL CHEMISTRY LETTERS, 2011, 2 (08) :608-613
[3]   Does oxidative stress contribute to the pathology of Friedreich's ataxia? A radical question [J].
Armstrong, Jeffrey S. ;
Khdour, Omar ;
Hecht, Sidney M. .
FASEB JOURNAL, 2010, 24 (07) :2152-2163
[4]   Neurodegenerative diseases and oxidative stress [J].
Barnham, KJ ;
Masters, CL ;
Bush, AI .
NATURE REVIEWS DRUG DISCOVERY, 2004, 3 (03) :205-214
[5]   Coenzyme Q - Biosynthesis and functions [J].
Bentinger, Magnus ;
Tekle, Michael ;
Dallner, Gustav .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2010, 396 (01) :74-79
[6]   Improved synthesis of EM-1745, preparation of its C17-ketone analogue and comparison of their inhibitory potency on 17β-hydroxysteroid dehydrogenase type 1 [J].
Berube, Marie ;
Poirier, Donald .
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY, 2009, 24 (03) :832-843
[7]   Plasma coenzyme Q10 response to oral ingestion of coenzyme Q10 formulations [J].
Bhagavan, Hemmi N. ;
Chopra, Raj K. .
MITOCHONDRION, 2007, 7 :S78-S88
[8]   Programmed cell death via mitochondria: Different modes of dying [J].
Bras, M ;
Queenan, B ;
Susin, SA .
BIOCHEMISTRY-MOSCOW, 2005, 70 (02) :231-+
[9]   Oxidative stress, mitochondrial dysfunction and cellular stress response in Friedreich's ataxia [J].
Calabrese, V ;
Lodi, R ;
Tonon, C ;
D'Agata, V ;
Sapienza, M ;
Scapagnini, G ;
Mangiameli, A ;
Pennisi, G ;
Stella, AMG ;
Butterfield, DA .
JOURNAL OF THE NEUROLOGICAL SCIENCES, 2005, 233 (1-2) :145-162
[10]   HYDROPEROXIDE METABOLISM IN MAMMALIAN ORGANS [J].
CHANCE, B ;
SIES, H ;
BOVERIS, A .
PHYSIOLOGICAL REVIEWS, 1979, 59 (03) :527-605
12345