PROTEOMIC AND MOLECULAR ASPECTS OF ATROPHY IN MAMMALIAN MUSCLES: LESSONS FROM BATS AND RATS

© TaesikGwag, KisooLee, HyunwooJu, BeomseokSong, JuwoonLee, MyungwooByun, InhoChoi
© Государственный музей истории космонавтики им. К.Э. Циолковского, г. Калуга
Секция "К.Э. Циолковский и проблемы космической медицины и биологии"
2008 г.

As a first step to overcome the problems of muscle atrophy during the long-term space flight, we investigated expression levels of contractile and stress proteins using 2-dimenstional electrophoresis, and activation of signaling molecules associated with muscle protein synthesis using immunoblotting analysis on the pectoral muscle of bat Murina leucogaster and the soleus muscle of Sprague-Dawley rats. Mammalian hibernators are known to exhibit almost no atrophy of skeletal muscles over 4—6 months of winter dormancy. This is contrasted by the muscles of non-hibernators including rats and humans which show significant reduction in muscle mass and tension production even after 2—3 weeks of inactivity. Bats were collected in mid-summer and mid-winter (~ 3 months of hibernation, HB) from their natural hibernaculum. The rats were divided into a vivarium control and a 3-wk hindlimb suspension group (HS). We found the rat soleus muscle showed 31—50 % reduction in the relative muscle mass and maximum tetanic tension for the 3-wk unloading, whereas the bat pectoral muscle did not show any sign of atrophy or functional depression for 3-mo dormancy. Expressions of sarcomeric proteins (alpha-actin, tropomyosin, myosin light chain, troponin T) and heat shock proteins (HSP90, p27, alpha B crystalline) of the HS group decreased 0.3 - to 0.7-fold those of the control, while expressions of most of these proteins were maintained or even elevated 1.7- to 1.9-fold for HSP70 and HSP27 in the HB group. In the signaling pathways, activation of both protein kinase B/Akt1 and FoxO was significantly reduced in the rat muscle, whereas activation of these molecules were differentially regulated in the bat pectoral muscle. Because the chaperone molecules (HSPs) play a crucial role for maintenance of protein turnover and myofibrillar integrity against stresses, differences in the stress protein expression would be an important factor limiting the extent of muscle atrophy and contractile depression over the prolonged inactivity. Moreover, the differential activation of the signaling molecules may allow the bats to retain muscle mass and tension production even after the long period of winter dormancy.