Kim S S, Rhee S, Lee K H, Kim J H, Kim H S, Kang M S, Chung C H
Department of Molecular Biology and Research Center for Cell Differentiation, College of Natural Sciences, Seoul National University, South Korea.
FEBS Lett. 1998 Aug 14;433(1-2):47-50. doi: 10.1016/s0014-5793(98)00883-7.
Myogenesis is characterized by membrane fusion and accumulation of muscle specific proteins. We have previously shown that nitric oxide acts as a messenger for membrane fusion. Here we show that inhibitors of the proteasome, such as lactacystin, reversibly block both the fusion of L6 myoblasts and the accumulation of muscle specific proteins, such as myosin heavy chain (MHC). The inhibitors also reversibly prevented the induction of the NF-kappaB activity, which is required for the expression of nitric oxide synthase (NOS). Moreover, the inhibition of the NF-kappaB activity occurred in parallel with that of the NOS activity upon treatment with increasing concentrations of lactacystin. While pyrrolidine dithiocarbamate, an inhibitor of NF-kappaB, blocked both membrane fusion and accumulation of MHC, N(G)-monomethyl-L-arginine, a specific inhibitor of NOS, inhibited only the fusion. These results suggest that the proteasome plays an essential role in the regulation of myogenic differentiation through the activation of NF-kappaB and that the target of NF-kappaB for the expression of muscle specific proteins is distinct from that for myoblast fusion.
肌生成的特征是膜融合和肌肉特异性蛋白质的积累。我们之前已经表明，一氧化氮作为膜融合的信使。在此我们表明，蛋白酶体抑制剂，如乳胞素，可可逆地阻断L6成肌细胞的融合以及肌肉特异性蛋白质如肌球蛋白重链（MHC）的积累。这些抑制剂还可逆地阻止了一氧化氮合酶（NOS）表达所需的NF-κB活性的诱导。此外，在用增加浓度的乳胞素处理时，NF-κB活性的抑制与NOS活性的抑制同时发生。虽然NF-κB抑制剂吡咯烷二硫代氨基甲酸盐可阻断膜融合和MHC的积累，但NOS特异性抑制剂N（G）-单甲基-L-精氨酸仅抑制融合。这些结果表明，蛋白酶体通过激活NF-κB在肌源性分化的调节中起重要作用，并且NF-κB用于肌肉特异性蛋白质表达的靶标与成肌细胞融合的靶标不同。
