Skeletal muscle gene expression in space‐flown rats

Abstract

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.

Proteomic Analysis of Mouse Hypothalamus under Simulated Microgravity

“…In brief the hypothalamus was suspended in isoelectrofocusing buffer containing 20 mM Tris, 7 M urea, 2 M thiourea, 4% CHAPS, 10 mM 1,4-dithioerythritol, 0.5% ampholyte [3][4][5][6][7][8][9][10] and a mixture of protease inhibitors (1 tablet Complete TM Roche Diagnostics) per 10 ml of suspension buffer). The suspension was sonicated for approximately 30 s and centrifuged at 100,000× g for 30 min.…”

“…The sensitivity of the mammalian central nervous system to gravitational influences involves both direct and indirect factors. It has been shown earlier that changes in the gravitational environment might represent a useful tool to investigate the neurobiological and behavioral responses to stressors and may provide insights into the mechanisms underlying development and plasticity of the brain, the heart, and the lung [1,[4][5][6]. The neurophysiological basis for adaptive phenomena in recurrent vestibular stimulation has been found to reside partly in the vestibular nuclei of the medulla, and not to require integrity of connections with higher vestibular centers, such as vestibular ganglion.…”

The effect of microgravity on tissue structure and function of rat testis

“…Therefore, decrements in bone and muscle mass are major concerns in extended space missions (10,34). Several studies have identified the factors that cause decrements in bone and muscle mass (35,36). In recent years, a specific role of androgens in skeletal homeostasis has been proposed (37).…”

Effects of alfacalcidol on circulating cytokines and growth factors in rat skeletal muscle

“…During muscle atrophy, including that induced by fasting [19][20][21][22], the expression of MuRF-1 and MAFbx have been reported to be increased. MuRF-1 ubiquitinates myofibrillar and cytoskeleton proteins and metabolic enzymes in preparation for their subsequent breakdown in the proteasome [57][58][59][60].…”

“…Elevated levels of interleukin 6 (IL-6) may also reduce food intake [17] and contribute to muscle wasting via abolishing the normally anabolic effect of insulin-like growth factor 1 (IGF-1) [18]. The muscle breakdown may be realised by an increased expression of the muscle specific ubiquitin ligases, MAFbx and MuRF-1, that play an important role in protein breakdown, as observed during undernutrition [19][20][21][22] and systemic inflammation [23]. It is thus possible that undernutrition and inflammation may induce the expression of the muscle specific E3 ubiquitin ligases and thereby contribute to the loss of body and muscle mass during alfacalcidol supplementation.…”