Spaceflight Environment Induces Mitochondrial Oxidative Damage in Ocular Tissue

被引:82
作者
Mao, Xiao W. [1 ,2 ]
Pecaut, Michael J. [1 ,2 ]
Stodieck, Louis S. [3 ]
Ferguson, Virginia L. [3 ]
Bateman, Ted A. [4 ]
Bouxsein, Mary [5 ]
Jones, Tamako A. [1 ,2 ]
Moldovan, Maria [1 ,2 ]
Cunningham, Christopher E. [1 ,2 ]
Chieu, Jenny [1 ,2 ]
Gridley, Daila S. [1 ,2 ]
机构
[1] Loma Linda Univ, Dept Basic Sci, Div Radiat Res, Loma Linda, CA 92354 USA
[2] Loma Linda Univ, Med Ctr, Loma Linda, CA USA
[3] Univ Colorado, BioServe Space Technol, Boulder, CO 80309 USA
[4] Univ N Carolina, Dept Radiat Oncol, Chapel Hill, NC 27515 USA
[5] Harvard Univ, Sch Med, Dept Orthoped Surg, Boston, MA 02115 USA
关键词
DURATION SPACE-FLIGHT; NITRIC-OXIDE; CELL-DEATH; PRECURSOR CELLS; GROWTH-FACTOR; IN-VIVO; STRESS; APOPTOSIS; RETINA; DEGENERATION;
D O I
10.1667/RR3309.1
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
A recent report shows that more than 30% of the astronauts returning from Space Shuttle missions or the International Space Station (ISS) were diagnosed with eye problems that can cause reduced visual acuity. We investigate here whether spaceflight environment-associated retinal damage might be related to oxidative stress-induced mitochondrial apoptosis. Female C57BL/6 mice were flown in the space shuttle Atlantis (STS-135), and within 3-5 h of landing, the spaceflight and ground-control mice, similarly housed in animal enclosure modules (AEMs) were euthanized and their eyes were removed for analysis. Changes in expression of genes involved in oxidative stress, mitochondrial and endothelial cell biology were examined. Apoptosis in the retina was analyzed by caspase-3 immunocytochemical analysis and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay. Levels of 4-hydroxynonenal (4-HNE) protein, an oxidative specific marker for lipid peroxidation were also measured. Evaluation of spaceflight mice and AEM ground-control mice showed that expression of several genes playing central roles in regulating the mitochondria-associated apoptotic pathway were significantly altered in mouse ocular tissue after spaceflight compared to AEM ground-control mice. In addition, the mRNA levels of several genes, which are responsible for regulating the production of reactive oxygen species were also significantly up-regulated in spaceflight samples compared to AEM ground-control mice. Further more, the level of HNE protein was significantly elevated in the retina after spaceflight compared to controls. Our results also revealed that spaceflight conditions induced significant apoptosis in the retina especially inner nuclear layer (INL) and ganglion cell layer (GCL) compared to AEM ground controls. The data provided the first evidence that spaceflight conditions induce oxidative damage that results in mitochondrial apoptosis in the retina. This data suggest that astronauts may be at increased risk for late retinal degeneration. (C) 2013 by Radiation Research Society
引用
收藏
页码:340 / 350
页数:11
相关论文
共 56 条
[1]  
[Anonymous], 2008, MAN SPAC RAD RISK NE
[2]   Environmental Enrichment Extends Photoreceptor Survival and Visual Function in a Mouse Model of Retinitis Pigmentosa [J].
Barone, Ilaria ;
Novelli, Elena ;
Piano, Ilaria ;
Gargini, Claudia ;
Strettoi, Enrica .
PLOS ONE, 2012, 7 (11)
[3]   Nitric oxide-induced mitochondrial fission is regulated by dynamin-related GTPases in neurons [J].
Barsoum, Mark J. ;
Yuan, Hua ;
Gerencser, Akos A. ;
Liot, Geraldine ;
Kushnareva, Yulia E. ;
Graeber, Simone ;
Kovacs, Imre ;
Lee, Wilson D. ;
Waggoner, Jenna ;
Cui, Jiankun ;
White, Andrew D. ;
Bossy, Blaise ;
Martinou, Jean-Claude ;
Youle, Richard J. ;
Lipton, Stuart A. ;
Ellisman, Mark H. ;
Perkins, Guy A. ;
Bossy-Wetzel, Ella .
EMBO JOURNAL, 2006, 25 (16) :3900-3911
[4]   The role of oxidative stress in the pathogenesis of age-related macular degeneration [J].
Beatty, S ;
Koh, HH ;
Henson, D ;
Boulton, M .
SURVEY OF OPHTHALMOLOGY, 2000, 45 (02) :115-134
[5]   Light-induced degeneration and microglial response in the retina of an epibenthonic pigmented teleost: age-dependent photoreceptor susceptibility to cell death [J].
Bejarano-Escobar, Ruth ;
Blasco, Manuel ;
Martin-Partido, Gervasio ;
Francisco-Morcillo, Javier .
JOURNAL OF EXPERIMENTAL BIOLOGY, 2012, 215 (21) :3799-3812
[6]   A mitochondrial perspective on cell death [J].
Bernardi, P ;
Petronilli, V ;
Di Lisa, F ;
Forte, M .
TRENDS IN BIOCHEMICAL SCIENCES, 2001, 26 (02) :112-117
[7]   H2O2 and genistein differentially modulate protein tyrosine phosphorylation, endothelial morphology, and monolayer barrier function [J].
Carbajal, JM ;
Schaeffer, RC .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1998, 249 (02) :461-466
[8]   Biological impact of low dose-rate simulated solar particle event radiation in vivo [J].
Chang, P. Y. ;
Doppalapudi, R. ;
Bakke, J. ;
Wang, A. ;
Menda, S. ;
Davis, Z. .
RADIATION AND ENVIRONMENTAL BIOPHYSICS, 2010, 49 (03) :379-388
[9]  
Chen Hai-Long, 2009, Shengli Xuebao, V61, P108
[10]   Alternative pathway of cell death in Drosophila mediated by NF-κB transcription factor Relish [J].
Chinchore, Yashodhan ;
Gerber, Gloria F. ;
Dolph, Patrick J. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2012, 109 (10) :E605-E612