The speed of contraction of a skeletal muscle largely depends on the myosin heavy chain isoforms (MyHC), whereas the relaxation is initiated and maintained by the sarcoplasmic reticulum Ca²⁺-ATPases (SERCA). The expression of the slow muscle-type myosin heavy chain I (MyHCI) is entirely dependent on innervation, but, as we show here, innervation is not required for the expression of the slow-type sarcoplasmic reticulum Ca²⁺-ATPase (SERCA2a) in regenerating soleus muscles of the rat, although it can play a modulator role. Remarkably, the SERCA2a level is even higher in denervated than in innervated regenerating soleus muscles on day 7 when innervation is expected to resume. Later, the level of SERCA2a protein declines in denervated regenerated muscles but it remains expressed, whereas the corresponding mRNA level is still increasing. SERCA1 (i.e., the fast muscle-type isoform) expression shows only minor changes in denervated regenerating soleus muscles compared with innervated regenerating controls. When the soleus nerve was transected instead of the sciatic nerve, SERCA2a and MyHCI expressions were found to be even more uncoupled because the MyHCI nearly completely disappeared, whereas the SERCA2a mRNA and protein levels decreased much less. The transfection of regenerating muscles with constitutively active mutants of the Ras oncogene, known to mimic the effect of innervation on the expression of MyHCI, did not affect SERCA2a expression. These results demonstrate that the regulation of SERCA2a expression is clearly distinct from that of the slow myosin in the regenerating soleus muscle and that SERCA2a expression is modulated by neuronal activity but is not entirely dependent on it.

The 20-hydroxyecdysone (20E) has been used in traditional medicine for a long time and acquired attention in the last decade as a food supplement and stimulant in physical activities. This polyhydroxylated cholesterol is found in the highest concentration in plants, and it is one of the secondary plant products that has a real hormonal influence in arthropods. Various beneficial effects have been reported in vivo and in vitro for 20E and its related compounds in mammals. Trials for the safety of clinical application showed a remarkably high tolerance in humans. This review aims to assess the latest development in the involvement of various pathways in tissues and organs and look if it is plausible to find a single primary target of this compound. The similarities with agents mimicking calorie restriction and anti-aging effects are also elucidated and discussed.