Tail-suspension induces altered expression of GAPDH and ZAKI-4-beta mRNAs in rat hindlimbs: Implication for disuse muscle atrophy

Abstract

Disuse atrophy of skeletal muscle is a serious complication for a number of bed-ridden patients. It has previously been demonstrated that unloading of hindlimb muscles by rat tail-suspension for 7 days resulted in disuse atrophy. This is characterized by the change from slow-twitch-oxidative to fast-twitch-glycolytic muscle fibers. Glyceraidehyde-3 phosphate dehydrogenase (GAPDH) is an important glycolytic enzyme in muscles. On the other hand calcineurin (Cn) plays important roles to change fiber subtypes of skeletal muscle. Since it has recently been demonstrated that ZAKI-4 beta, an inhibitor of Cn, is expressed in skeletal muscles, the changes in the expression of GAPDH and ZAKI-4 beta mRNA after 7 days of tail-suspension in rats were investigated. It reduced the body weight gain (20 g) which was about one third of that of control group (60 g). Thus the weights of muscles were corrected by body weight. The weight of gastrocnemius and soleus decreased significantly by the tail suspension. In the control group, abundance of GAPDH mRNA in the gastrocnemius was ten times higher than that in soleus. Tail-suspension significantly increased the abundance of GAPDH mRNA in soleus. The same tendency was observed in gastrocnemius without statistical significance. In the control group, the levels of ZAKI-4 beta mRNA in the soleus was about five times higher than that in gastrocnemius. In the suspended group, ZAKI-4 beta mRNA in the gastrocnemius decreased significantly but did not change in the soleus. The results of GAPDH mRNA suggest that fast-glycolytic fibers are more abundant in gastrocnemius than that in soleus before suspension and tail-suspension increased the ratio of this fiber type in soleus. On the other hand, ZAKI-4 beta mRNA seems to be expressed selectively in slow-twitch-oxidative fibers, which is compatible with the decreased ratio of slow-twitch fiber in gastrocnemius after the tail-suspension.