PROPOSAL OF A NEW COUNTERMEASURE FOR RED MUSCLE ATROPHY IN SPACE AND AGED PEOPLE: A KEY MOLECULAR CHAPERONE ALPHA B-CRYSTALLIN AS A PIVOTAL PLAYER FOR CELLULAR SUSTAINABLE DYNAMICS

摘要

Space biology contributes to health science especially in aging peoples, described as "The G-Connection" showingdisuse atrophy (1). In space we cannot utilize well own life system having large adaptability evolved under thegravity, of which clear property is endurance ability. Coactivator PGC1α facilitates both transcriptions of slowmuscle proteins to keep endurance and tonic contraction and mitochondrial genes supporting oxidative metabolismunder the gravity. Aerobic exercise, which is mainly produced by slow muscle, induces PGC-1α, which is beneficialfor protection of life-related diseases. Interestingly, microtubule destabilizing small molecules, like nocodazole/taxolare identified as regulators of PGC1α (2). Our body temperature is about 37 deg. In our study, the increasedtemperature to 39 deg induces PGC1αin cultured myoblasts to myotubes (3). All biological system has developedmolecular chaperone/stress protein system, which helps keeping protein structure normally, refolding denaturedform or breaking down it to proteasome and/or autophagy, most of them are 1 spacio-temporally regulated by thecytoskeleton. We have studied molecular chaperone, ?B-crystallin, which is constitutively expressed most in type Ⅰ,more in type IID/IIA but less in type IIB fibers in soleus/plantaris muscles (4). Recent studies show ?B-crystallinhas multi-functions working as chaperone for protein sequences to transfer mechanical stress from adhesive area tonucleus, keeping dynamics those pathways, maintaining integrin, and inhibiting caspase 3 activation againstmitochondrial apoptosis, and also facilitating protein degradation associating with denatured proteins to proteasomemachinery. We have identified ?B-crystallin as key molecule to solve mechanism of slow muscle atrophy (5) andshown important roles of ?B-crystallin keeping tubulin/microtubule dynamics (6-8). In this study, we try tovisualize molecular chaperone-supportive dynamics of striated muscles. Using beating cultured cardiac myocyte, weshow dynamic striated patterns of GFP-??B-crystallin, of which localization at Z-bands disappeared aftermicrotubule-destabilizing drug treatments. This indicates ?B-crystallin is deeply related to keeping dynamics underendurance tonic contraction. Some applied methods have been developed to induce ?B-crystallin and/or factorsconsisting of slow muscle like mechanical stretch (5,7), mild heat stress (3), and use of avian eggshell membrane (9).From these basic biological adaptive mechanism evolved on the earth, we propose strategy of gravity health scienceto protect against anti-gravitational muscle atrophy induced long journey to Mars by the human being and agedpeople.