抗酸化ビタミンおよびポリフェノールが骨格筋の適応および持久力に及ぼす影響

早大学位記番号:新7709早稲田大

Changes of cytokines in mouse skeletal muscle and plasma by a single bout of endurance exercise.

Introduction: Exercise influences some cytokine levels, which is considered the body’s reaction against endogenous stress. Previous human studies demonstrated that high intensity exercise contributes to a dramatic increase of plasma cytokines like Interleukin-6 (IL-6) and Interleukin-1 receptor antagonist (IL-1ra) immediately after exercise. Recently, it has been identified that skeletal muscle produces cytokines and peptides and they exert both paracrine and endocrine effects. However, the sequential changes of cytokine production according to exercise conditions such as intensity, types and working time are still unclear. In this study, we identified the sequential changes of cytokines in both skeletal muscle and plasma after acute endurance exercise. Methods: Male C57BL/6 mice (n=35) were randomized to a sedentary or a treadmill running group (25m/min, 0% grade). To examine the sequential changes of cytokines, the exercise group was divided into 3 groups and each group was sacrificed at different time points (Post-exercise 0, 2, and 6 hours). Skeletal muscle and plasma were taken and real-time PCR and ELISA were conducted. The mRNA expression of IL-6, IL-7, IL-15, Myostatin, Irisin, Leukaemia inhibitory factor (LIF), IL-1ra and IL-1beta in skeletal muscle was identified by real-time PCR. The protein concentrations of IL-6, IL-1ra, Monocyte chemotactic protein 1 (MCP-1), and Myeloperoxidase (MPO) in plasma were investigated by ELISA. Also, IL-6 protein concentration in skeletal muscle was measured by ELISA. Results: IL-6 mRNA expression in skeletal muscle increased at 6 hrs post-exercise compared with pre-exercise, immediately post-exercise and 2 hrs post-exercise. In contrast, IL-6 protein concentration in skeletal muscle was decreased significantly 2 and 6 hrs post-exercise compared with pre-exercise and immediately post-exercise. However, there was no significant change in IL-6 protein levels in plasma. Also, there were no significant changes in IL-7, IL-15, Myostatin, Irisin, LIF, IL-1ra and IL-1beta mRNA levels at each time point. Conclusions: A single bout of endurance exercise in mice altered IL-6 mRNA and protein expression in skeletal muscle in a delayed onset manner. However, there has no effect on IL-7, IL-15, Myostatin, Irisin, LIF, IL-1ra and IL-1beta mRNA expression in skeletal muscle and the plasma concentrations of IL-6, IL-1ra, MCP-1, and MPO

Genome-Wide Analysis of Acute Endurance Exercise-Induced Translational Regulation in Mouse Skeletal Muscle

<div><p>Exercise dynamically changes skeletal muscle protein synthesis to respond and adapt to the external and internal stimuli. Many studies have focused on overall protein synthesis to understand how exercise regulates the muscular adaptation. However, despite the probability that each gene transcript may have its own unique translational characteristics and would be differentially regulated at translational level, little attention has been paid to how exercise affects translational regulation of individual genes at a genome-wide scale. Here, we conducted a genome-wide translational analysis using ribosome profiling to investigate the effect of a single bout of treadmill running (20 m/min for 60 min) on mouse gastrocnemius. Global translational profiles largely differed from those in transcription even at a basal resting condition as well as immediately after exercise. As for individual gene, Slc25a25 (Solute carrier family 25, member 25), localized in mitochondrial inner membrane and maintaining ATP homeostasis and endurance performance, showed significant up-regulation at translational level. However, multiple regression analysis suggests that Slc25a25 protein degradation may also have a role in mediating Slc25a25 protein abundance in the basal and early stages after acute endurance exercise.</p></div

Macrophage depletion by clodronate liposome attenuates muscle injury and inflammation following exhaustive exercise

Exhaustive exercise promotes muscle injury, including myofiber lesions; however, its exact mechanism has not yet been elucidated. In this study, we tested the hypothesis that macrophage depletion by pretreatment with clodronate liposomes alters muscle injury and inflammation following exhaustive exercise. Male C57BL/6J mice were divided into four groups: rest plus control liposome (n=8), rest plus clodronate liposome (n=8), exhaustive exercise plus control liposome (n=8), and exhaustive exercise plus clodronate liposome (n=8). Mice were treated with clodronate liposome or control liposome for 48 h before undergoing exhaustive exercise on a treadmill. Twenty-four hours after exhaustive exercise, the gastrocnemius muscles were removed for histological and PCR analyses. Exhaustive exercise increased the number of macrophages in the muscle; however, clodronate liposome treatment reduced this infiltration. Although exhaustive exercise resulted in an increase in injured myofibers, clodronate liposome treatment following exhaustive exercise reduced the injured myofibers. Clodronate liposome treatment also decreased the mRNA expression levels of inflammatory cytokines (TNF-α, IL-1β, and IL-6) in the skeletal muscle after exhaustive exercise. These results suggest that macrophages play a critical role in increasing muscle injury by regulating inflammation