Molecular Mechanisms of Muscle Redox Signaling in Exercise and Injury

运动和损伤中肌肉氧化还原信号传导的分子机制

• 批准号: 19K11560
• 负责人: Wolf Alexander
• 金额: $ 2.83万
• 依托单位: Nippon Medical School
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2019
• 资助国家: 日本
• 起止时间: 2019-04-01 至 2022-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-19K11560/
• 关键词: レドックス; 酸化ストレス; 運動; redox; exercise; injury; roGFP; imaging; in vivo imaging

Exercise remains the most powerful intervention to increase health span in humans and is widely advocated to slow down or even prevent the functional decline occurring in old age. Exercise builds muscle mass, which prevents frailty, increases mobility, as a consequence, quality of life. Nevertheless, the molecular mechanisms by which exercise builds muscle mass are not well understood. Oxidative stress has long been seen as a negative consequence of exercise, but more recent results suggest that reducing oxidative stress can prevents the beneficial effects of exercise, underscoring its importance in signaling during training.Using transgenic mice expressing a ratiometric redox-sensitive fluorescent protein (roGFP) in mitochondrial or cytosol, we will record the spatio-temporal dynamics of cellular redox state in skeletal muscle of live animals using in vivo imaging. We already found that muscle fiber injury plays an important role in redox signaling during exercise and accompanying muscle fiber injury, but did not yet identify the pathway(s) transmitting this signal. We will work towards identifying the danger associated molecular patterns (DAMPs) released by injured muscle fibers and the receptors causing the observed redox transients in adjacent tissue. Suitable in vitro models will also be employed, with the overall goal of gaining insights that might help design interventions that increase the positive effects of exercise.One publication and one book chapter was published during parental leave.

运动仍然是延长人类健康寿命的最有力的干预措施，并被广泛主张减缓甚至预防老年时发生的功能衰退。锻炼可以增强肌肉质量，从而防止虚弱，提高活动能力，从而提高生活质量。然而，运动增强肌肉质量的分子机制尚不清楚。氧化应激长期以来一直被视为运动的负面后果，但最近的研究结果表明，减少氧化应激可以阻止运动的有益效果，强调了其在训练过程中信号传导的重要性。使用在线粒体或细胞质中表达比例氧化还原敏感荧光蛋白（roGFP）的转基因小鼠，我们将记录骨骼中细胞氧化还原状态的时空动态。 使用体内成像来观察活体动物的肌肉。我们已经发现肌纤维损伤在运动期间和伴随的肌纤维损伤期间的氧化还原信号传导中发挥重要作用，但尚未确定传输该信号的途径。我们将努力识别受损肌纤维释放的危险相关分子模式 (DAMP) 以及导致邻近组织中观察到的氧化还原瞬变的受体。还将采用合适的体外模型，总体目标是获得见解，这可能有助于设计增加运动积极效果的干预措施。育儿假期间出版了一份出版物和一本书的章节。

项目成果

最新皮膚エイジングメカニズムと高機能性シワ改善化粧品の開発 - ブルーライトによる光老化のメカニズムと予防

最新皮肤老化机制及高机能抗皱化妆品开发-蓝光引起的光老化机制及预防

• 发表时间: 2020
• 作者: 可西 泰修;鎌田 浩史;渡邊 將司;都丸 洋平;中川 将吾;塚越 祐太;中島 亮一;山崎 正志;宮川 俊平;白木 仁;庄子博人,川島啓;ウォルフ アレクサンダー M.
• 通讯作者: ウォルフ アレクサンダー M.