2017 Fiscal Year Research-status Report
Oxidative stress in skeletal muscle exercise and injury
| Project/Area Number |
16K01736
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| Research Institution | Nippon Medical School |
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Principal Investigator |
Wolf Alexander 日本医科大学, 先端医学研究所, 講師 (20434136)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Keywords | 運動 / 酸化ストレス / 活性酸素 / roGFP / DAMPs / injury |
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| Outline of Annual Research Achievements |
Physical exercise enhances fitness and overall health and wellness. Bouts of aerobic and anaerobic exercise induce an acute state of oxidative stress caused by an increase in reactive oxygen species (ROS), but there is little agreement which processes generate ROS and where, if they are important and how they are controlled. We produced transgenic mice expressing redox-sensitive GFP in skeletal muscle, and set up imaging systems to record muscle redox state in live anesthetized animals. Determining the conditions necessary for induction of oxidative stress during skeletal muscle activation in mice in vivo, preliminary experiments indicated that some amount of muscle fiber injury is necessary to induce oxidative stress during skeletal muscle activation. Simple electrical stimulation of muscle did not induce oxidation of the skeletal muscle glutathione pool. Injured muscle fibers became oxidized, but this oxidation did not spread to adjacent fibers in the absence of muscle activation.
In the last year, we successfully implemented a system to produce precise and repeatable microscopic thermal injuries with a fiber-coupled infrared laser (1.5W,1470 nm), which allowed us to record compartmentalized (meaning separate measurements for cytosol and mitochondrial) redox state and injury-mediated redox signaling during simulated exercise with unprecedented sensitivity and single cell resolution. We also discovered similar redox transients in skin injury.
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| Current Status of Research Progress |
Current Status of Research Progress
3: Progress in research has been slightly delayed.
Reason
Using our infrared laser system to produce a microscopic thermal injuries, we could confirm our previous findings using mechanical injury. Considerable variability is still observed due to different amounts of of erythrocytes that leak from injured blood vessels and interfere with fluorescence ratio recordings. Nevertheless, experiments are expected to proceed mostly as planned. Due to an upcoming relocation of the research department including the movement of animal facilities, we will limit the dissection the molecular pathways of oxidative stress signalling mediated by danger-associated molecular patterns released from injured cells to pharmacologic interventions. The incorporation of genetic interventions will be delayed.
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| Strategy for Future Research Activity |
We will focus on preparing our findings up to now for publication: that oxidative stress occurs not immediately but within minutes after injury, in live mouse muscle and skin, but is absent in muscle activation without injury. We also plan to include some pharmacologic interventions to illustrate which signalling pathways are involved.
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| Causes of Carryover |
32603円を残しています。
今年度で使う必要がなかったので次年度に使用します。
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