Ubiquinol promotes retinal ganglion cell survival and blocks the apoptotic pathway in ischemic retinal degeneration

被引:24
作者
Ju, Won-Kyu [1 ]
Shim, Myoung Sup [1 ,3 ]
Kim, Keun-Young [2 ]
Bu, Jung Hyun [1 ]
Park, Tae Lim [1 ]
Ahn, Sangphil [1 ]
Weinreb, Robert N. [1 ]
机构
[1] Univ Calif San Diego, Dept Ophthalmol, Hamilton Glaucoma Ctr, Shiley Eye Inst, 9415 Campus Point Dr, La Jolla, CA 92037 USA
[2] Univ Calif San Diego, Dept Neurosci, Natl Ctr Microscopy & Imaging Res, La Jolla, CA 92093 USA
[3] Duke Univ, Dept Ophthalmol, Durham, NC USA
关键词
Ubiquinol; Retina; lschemia; Retinal ganglion cell; Apoptosis; TRIGGERS OPA1 RELEASE; COENZYME Q(10); OXIDATIVE STRESS; NEURODEGENERATIVE DISEASES; MITOCHONDRIAL ALTERATION; TRANSIENT ISCHEMIA; PROAPOPTOTIC BAX; OPTIC-NERVE; IN-VIVO; DEATH;
D O I
10.1016/j.bbrc.2018.08.016
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
Coenzyme Q10 (CoQ(10)) protects retinal ganglion cells (RGCs) in experimental retinal ischemia and glaucoma by scavenging reactive oxygen species. We tested whether a diet supplemented with ubiquinol, the reduced form of CoQ(10), promotes RGC survival and blocks the apoptotic pathway in ischemic mouse retina induced by acute high intraocular pressure (IOP) elevation. Ubiquinol (1%) treatment significantly promoted RGC survival at 2 weeks after ischemia/reperfusion. The ubiquinol treatment significantly blocked activation of astroglial and microglial cells in the ischemic retina at 2 weeks. While the ubiquinol treatment significantly decreased active Bax protein expression in the ischemic retina, phosphorylation of Bad at serine 112 and Bcl-xL protein expression were preserved in the ubiquinol-treated ischemic retina at 12 h. Consistently, the ubiquinol treatment prevented apoptotic cell death by blocking caspase-3 cleavage. These results suggest that the ubiquinol enhances RGC survival by modulating the Bax/Bad/Bcl-xL-mediated apoptotic pathway in the ischemic retina. Ubiquinol has therapeutic potential for ameliorating elevated IOP-induced ischemic retinal degeneration. (C) 2018 Elsevier Inc. All rights reserved.
引用
收藏
页码:2639 / 2645
页数:7
相关论文
共 31 条
[1]   Inhibition of Bax channel-forming activity by Bcl-2 [J].
Antonsson, B ;
Conti, F ;
Ciavatta, A ;
Montessuit, S ;
Lewis, S ;
Martinou, I ;
Bernasconi, L ;
Bernard, A ;
Mermod, JJ ;
Mazzei, G ;
Maundrell, K ;
Gambale, F ;
Sadoul, R ;
Martinou, JC .
SCIENCE, 1997, 277 (5324) :370-372
[2]   Coenzyme Q10 administration and its potential for treatment of neurodegenerative diseases [J].
Beal, MF .
BIOFACTORS, 1999, 9 (2-4) :261-266
[3]  
Beal MF, 1997, MOL ASPECTS MED, V18, pS169
[4]  
Beal MF, 2003, BIOFACTORS, V18, P153
[5]   Coenzyme Q10: Absorption, tissue uptake, metabolism and pharmacokinetics [J].
Bhagavan, HN ;
Chopra, RK .
FREE RADICAL RESEARCH, 2006, 40 (05) :445-453
[6]   Mitochondria as the central control point of apoptosis [J].
Desagher, S ;
Martinou, JC .
TRENDS IN CELL BIOLOGY, 2000, 10 (09) :369-377
[7]   Enhanced sensitivity of ubiquinone-deficient mutants of Saccharomyces cerevisiae to products of autoxidized polyunsaturated fatty acids [J].
Do, TQ ;
Shultz, JR ;
Clarke, CF .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (15) :7534-7539
[8]   Specificity of coenzyme Q10 for a balanced function of respiratory chain and endogenous ubiquinone biosynthesis in human cells [J].
Fernández-Ayala, DJM ;
López-Lluch, G ;
García-Valdés, M ;
Arroyo, A ;
Navas, P .
BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS, 2005, 1706 (1-2) :174-183
[9]   UBIQUINOL-10 IS AN EFFECTIVE LIPID-SOLUBLE ANTIOXIDANT AT PHYSIOLOGICAL CONCENTRATIONS [J].
FREI, B ;
KIM, MC ;
AMES, BN .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1990, 87 (12) :4879-4883
[10]   Sex-dependent co-occurrence of hypoxia and β-amyloid plaques in hippocampus and entorhinal cortex is reversed by long-term treatment with ubiquinol and ascorbic acid in the 3 x Tg-AD mouse model of Alzheimer's disease [J].
Frontinan-Rubio, Javier ;
Sancho-Bielsa, Francisco J. ;
Peinado, Juan R. ;
LaFeria, Frank M. ;
Gimenez-Llort, Lydia ;
Duran-Prado, Mario ;
Alcain, Francisco J. .
MOLECULAR AND CELLULAR NEUROSCIENCE, 2018, 92 :67-81