Leeuw T, Pette D
Faculty of Biology, University of Konstanz, Germany.
Dev Genet. 1996;19(2):163-8. doi: 10.1002/(SICI)1520-6408(1996)19:2<163::AID-DVG8>3.0.CO;2-7.
Skeletal muscle fibers are versatile entities, capable of changing their phenotype in response to altered functional demands. In the present study, fast-to-slow fiber type transitions were induced in rabbit tibialis anterior (fA) muscles by chronic low-frequency stimulation (CLFS). The time course of changes in relative protein concentrations of fast and slow myosin light chain (MLC) isoforms and changes in their relative synthesis rates by in vivo labeling with [35S]methionine were followed during stimulation periods of up to 60 days. Generally, relative synthesis rates and protein concentrations changed in parallel; i.e., fast isoforms decreased and slow isoforms increased. MLC3f, however, which turns over at a higher rate than the other light chains, exhibited a conspicuous discrepancy between a markedly reduced relative synthesis but only a moderate decrease in protein amount during the initial 2 weeks of CLFS. Apparently, MLC3f is regulated independent of MLC1f, with protein degradation playing an important role in its regulation. The exchange of fast MLC isoforms with their slow counterparts seemed to correspond to the ultimate fast-to-slow (MHCIIa-->MHCI) transition at the MHC level. However, due to an earlier onset of the fast-to-slow transition of the regulatory light chain and the delayed fast-to-slow exchange of the alkali light chains, a spectrum of hybrid isomyosins composed of fast and slow light and heavy chains must have existed transiently in transforming fibers. Such hybrid isomyosins appeared to be restricted to MHCIIa- and MHCI-based combinations. In conclusion, fiber type specific programs that normally coordinate the expression of myofibrillar protein isoforms seem to be maintained during fiber type transitions. Possible differences in post-transcriptional regulation may result in the transient accumulation of atypical combinations of fast and slow MLC and MHC isoforms, giving rise to the appearance of hybrid fibers under the conditions of forced fiber type conversion.
骨骼肌纤维是多功能的实体，能够根据功能需求的改变而改变其表型。在本研究中，通过慢性低频刺激（CLFS）在兔胫前肌（fA）中诱导快肌纤维向慢肌纤维类型的转变。在长达60天的刺激期内，追踪了快肌和慢肌肌球蛋白轻链（MLC）同工型相对蛋白浓度的变化时间进程以及通过用[35S]甲硫氨酸进行体内标记其相对合成速率的变化。一般来说，相对合成速率和蛋白浓度平行变化；即，快肌同工型减少，慢肌同工型增加。然而，MLC3f的周转率高于其他轻链，在CLFS的最初2周内，其相对合成显著降低，但蛋白量仅适度减少，两者之间存在明显差异。显然，MLC3f的调节独立于MLC1f，蛋白降解在其调节中起重要作用。快肌MLC同工型与慢肌同工型的交换似乎与MHC水平上最终的快肌向慢肌（MHCIIa→MHCI）转变相对应。然而，由于调节性轻链的快肌向慢肌转变更早开始，碱性轻链的快肌向慢肌交换延迟，在转变的纤维中必然短暂存在由快肌和慢肌轻链和重链组成的一系列杂种异肌球蛋白。这种杂种异肌球蛋白似乎仅限于基于MHCIIa和MHCI的组合。总之，在纤维类型转变过程中，通常协调肌原纤维蛋白同工型表达的纤维类型特异性程序似乎得以维持。转录后调节的可能差异可能导致快肌和慢肌MLC及MHC同工型非典型组合的短暂积累，在强制纤维类型转换的条件下产生杂种纤维的外观。
