Nikawa Takeshi, Ishidoh Kazumi, Hirasaka Katsuya, Ishihara Ibuki, Ikemoto Madoka, Kano Mihoko, Kominami Eiki, Nonaka Ikuya, Ogawa Takayuki, Adams Gregory R, Baldwin Kenneth M, Yasui Natsuo, Kishi Kyoichi, Takeda Shin'ichi
Department of Nutrition, The University of Tokushima School of Medicine, 3-18-15 Kuramoto-cho, Tokushima 770-8503, Japan.
FASEB J. 2004 Mar;18(3):522-4. doi: 10.1096/fj.03-0419fje. Epub 2004 Jan 8.
Skeletal muscles are vulnerable to marked atrophy under microgravity. This phenomenon is due to the transcriptional alteration of skeletal muscle cells to weightlessness. To further investigate this issue at a subcellular level, we examined the expression of approximately 26,000 gastrocnemius muscle genes in space-flown rats by DNA microarray analysis. Comparison of the changes in gene expression among spaceflight, tail-suspended, and denervated rats revealed that such changes were unique after spaceflight and not just an extension of simulated weightlessness. The microarray data showed two spaceflight-specific gene expression patterns: 1) imbalanced expression of mitochondrial genes with disturbed expression of cytoskeletal molecules, including putative mitochondria-anchoring proteins, A-kinase anchoring protein, and cytoplasmic dynein, and 2) up-regulated expression of ubiquitin ligase genes, MuRF-1, Cbl-b, and Siah-1A, which are rate-limiting enzymes of muscle protein degradation. Distorted expression of cytoskeletal genes during spaceflight resulted in dislocation of the mitochondria in the cell. Several oxidative stress-inducible genes were highly expressed in the muscle of spaceflight rats. We postulate that mitochondrial dislocation during spaceflight has deleterious effects on muscle fibers, leading to atrophy in the form of insufficient energy provision for construction and leakage of reactive oxygen species from the mitochondria.
骨骼肌在微重力环境下极易发生显著萎缩。这种现象是由于骨骼肌细胞对失重状态产生转录改变所致。为了在亚细胞水平进一步研究这一问题，我们通过DNA微阵列分析检测了太空飞行大鼠约26,000个腓肠肌基因的表达情况。对太空飞行、尾部悬吊和去神经支配大鼠的基因表达变化进行比较后发现，太空飞行后的这种变化是独特的，并非仅仅是模拟失重状态的延伸。微阵列数据显示出两种太空飞行特异性基因表达模式：1）线粒体基因表达失衡，同时细胞骨架分子表达紊乱，包括假定的线粒体锚定蛋白、A激酶锚定蛋白和胞质动力蛋白；2）泛素连接酶基因MuRF-1、Cbl-b和Siah-1A表达上调，这些基因是肌肉蛋白质降解的限速酶。太空飞行期间细胞骨架基因的表达畸变导致细胞内线粒体错位。几种氧化应激诱导基因在太空飞行大鼠的肌肉中高度表达。我们推测，太空飞行期间线粒体错位对肌纤维产生有害影响，导致肌肉萎缩，表现为为肌肉构建提供的能量不足以及线粒体中活性氧的泄漏。
