Molecular cloning related to skeletal or muscle atrophy under microgravity

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The effect of 14 days of flight on the vertebrae of rapidly growing rats was studied. No significant difference (p>0.05) was observed between flight rats and ground controls with regard to mechanical hardness or bone mineral density. however, histological examination revealed irregular thickening of the endosteal surface of cortical bones in flight rats, whereas it was uniform in the ground controls. The relative area of lamellar bone showed a significant reduction (p<0.001) in the flight rats. These findings suggest that structural disturbances were due to retardation of endosteal modeling and remodeling. Next, the effects of 14 days of space-flight on beta-adrenoceptor (beta-AR), mitochondrial enzyme activities, and fiber type composition were studied in plantaris muscles. The maximum binding capacity of beta-AR (B max) was significantly lower (>29%) after flight, and the recovery was not complete after 9 days in a 1-G environment. The activity of succinate dehydrogenase (SDH) was measured in muscle samples <5 hr after flight and were found to normalize during 9 days of recovery. It is suggested that the space-flight-induced decrease of B max of beta-AR in plantaris was accompanied by a decreased activity of a mitochondrial inner-membrane enzyme, SDH.Finally, the expression of mRNA in paraspinal muscles between space-flight rats and ground controls was compared using mRNA differential display method in order to identify molecules related to muscle atrophy under microgravity. We found that 70 kDa heat-shock protein (HSP70) and its retated gene, TCP-1, were makedly elevated during 14 days of space-flight, while genes involved in mitochondrial metabolism (mitochondrial adenosine nuclease translocator, mitochondrial cytochrome oxidase subunits), aldolase A and myocyte-specific enhancer binding factor (MEF) were significantly decreased. Some new genes related to muscle atrophy were also detected and we studied the biological functions of these molecules.