di Maso N A, Haddad F, Zeng M, McCue S A, Baldwin K M
Department of Physiology and Biophysics, University of California, Irvine, California 92697, USA.
J Appl Physiol (1985). 2000 Feb;88(2):682-9. doi: 10.1152/jappl.2000.88.2.682.
Previously, we have reported that the combination of hindlimb suspension (HS) and thyroid hormone [triiodothyronine (T(3))] treatment induces the de novo expression of the fast IIb myosin heavy chain (MHC) gene in the soleus. Thus we tested the hypotheses that the induction of IIb MHC expression with HS + T(3) is prevented with denervation and that this IIb induction is regulated by transcriptional processes. Adult female rats were subjected to 2 wk of combined HS + T(3) in which one side of the lower leg was simultaneously denervated. HS + T(3) caused decreased expression of the slow type I MHC and concomitant increases in both the fast type IIx and IIb MHC isoforms in the intact soleus muscle. Denervation prevented the endogenous expression of the IIb MHC gene at both the protein and mRNA levels. Although HS + T(3) intervention was able to markedly increase the expression of the 2.6-kb IIb MHC promoter-reporter construct using direct gene transfer, this induction, however, was not inhibited by denervation. These findings collectively suggest that normal innervation is essential for inducing the unique expression of the IIb MHC in a slow muscle in response to HS + T(3); however, in the denervated muscle, there is a discordance between the regulation of the endogenous IIb MHC gene relative to the exogenous IIb MHC promoter-reporter construct.
此前，我们曾报道后肢悬吊（HS）与甲状腺激素[三碘甲状腺原氨酸（T(3)）]联合处理可诱导比目鱼肌中快肌IIb型肌球蛋白重链（MHC）基因的从头表达。因此，我们检验了以下假设：去神经支配可阻止HS + T(3)诱导IIb MHC表达，且这种IIb诱导受转录过程调控。成年雌性大鼠接受2周的HS + T(3)联合处理，其中一侧小腿同时进行去神经支配。HS + T(3)导致完整比目鱼肌中慢肌I型MHC表达降低，同时快肌IIx和IIb MHC亚型表达增加。去神经支配在蛋白质和mRNA水平均阻止了IIb MHC基因的内源性表达。尽管HS + T(3)干预通过直接基因转移能够显著增加2.6 kb IIb MHC启动子-报告基因构建体的表达，然而这种诱导并未被去神经支配所抑制。这些发现共同表明，正常的神经支配对于响应HS + T(3)诱导慢肌中IIb MHC的独特表达至关重要；然而，在去神经支配的肌肉中，内源性IIb MHC基因的调控与外源性IIb MHC启动子-报告基因构建体的调控之间存在不一致。
