[Anti-Atrophy]
Research on inhibitory effects of novel concept biomaterials, a HSP inducer and ubiquitin ligase inhibitor, on microgravity-induced muscle atrophy

RESEARCH OVERVIEW

• Muscle atrophy reduces the quality of life, not only for astronauts on long-duration missions, but also for the elderly on Earth. It is important to clarify the mechanisms that can lead to muscle atrophy.
• In the Research on Inhibitory Effects of Novel Concept Biomaterials, an HSP Inducer and Ubiquitin Ligase Inhibitor, on Microgravity-induced Muscle Atrophy (Anti-Atrophy) investigation, cells are incubated with and without biomaterials, such as muscle atrophy inhibitors or muscle synthesis accelerators. Comparing the cultured cells can help verify the effectiveness of the biomaterials to counter muscle atrophy.
• Results may lead to the production of pharmaceuticals to prevent muscle atrophy, not only for astronauts in space, but also for the elderly on Earth.

DESCRIPTION

Skeletal muscle is one of the most sensitive organs to mechanical stress. For example, it is easy for skeletal muscle to undergo atrophy under microgravity conditions, while exercise stimulates its growth. Several lines of investigation suggest that skeletal muscle cells possess unique sensors for mechanical stress. Based on previous studies, it is hypothesized that tension fluctuation in the sarcolemma (plasma membrane of skeletal muscle cells) plays an important role in sensing mechanical stress. Mechanical stress changes in tension fluctuation in sarcolemma, resulting in activation of channels and/or proteases on membrane surface. They transduce intracellular signaling in skeletal muscle cells to express muscle atrophy-associated ubiquitin ligases (atrogenes), including Cblin, MAFbx/atrogin-1, and MuRF-1.

In the Research on Inhibitory Effects of Novel Concept Biomaterials, an HSP Inducer and Ubiquitin Ligase Inhibitor, on Microgravity-induced Muscle Atrophy (Anti-Atrophy) investigation, the research team seeks to clarify the mechanism of how the tension fluctuation in sarcolemma regulate activities of such transducers under microgravity conditions. L6 myotube/myoblastic cells are cultured on an extracellular matrix with different rigidity, with and without added Cbl-b inhibitors, in the 'Kibo' module of the International Space Station (ISS).

SPACE APPLICATIONS

Biomaterials that can either slow muscle atrophy or accelerate muscle growth could supplement exercise as a countermeasure to muscle atrophy in space.

EARTH APPLICATIONS

People on Earth, particularly the elderly, also experience muscle atrophy. This investigation may advance development of pharmaceuticals to prevent muscle atrophy for people on Earth, as well as for astronauts.

OPERATIONAL REQUIREMENTS AND PROTOCOLS

• Right after the cargo vehicle arrival to the ISS, culture chambers are set up in the Measurement Experiment Unit (MEU), and installed into the Cell Biology Experiment Facility (CBEF) for incubation at 37°C, 5% CO², and 60% relative humidity.
• Two days after the incubation start, MEUs are retrieved from the CBEF temporarily for chemical treatments, such as medium exchange by Solution Exchanger, and biomaterial (C14Cblin) injection by using syringes.
• Five days after the incubation start, another biomaterial (Celastrol) injection is conducted.
• Six hours after the second injection, all samples are fixed by RNAlater. The fixed samples are stowed in the Minus Eighty Laboratory Freezer for ISS (MELFI) until return to Earth.