Signal transduction pathways, and nuclear translocation of zinc and metallothionein during differentiation of myoblasts.
Signal transduction pathways, and nuclear translocation of zinc and metallothionein during differentiation of myoblasts.
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DOI：
10.1139/o99-070
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发表时间：
2000
期刊：
影响因子：
--
通讯作者：
M. Apostolova;I. A. Ivanova;M. Cherian
中科院分区：
文献类型：
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作者：
M. Apostolova;I. A. Ivanova;M. Cherian
研究了两种成肌细胞株L6和H9C2分化过程中金属硫蛋白亚细胞定位的变化。添加胰岛素样生长因子- 1或将胎牛血清降至1%可诱导成肌细胞向肌管分化。金属硫蛋白和锌主要定位于成肌细胞的细胞质中，但在分化早期转移到新形成的肌管的细胞核中。在完全分化的肌管中，金属硫蛋白含量随着细胞质定位而降低。添加有丝分裂原活化蛋白激酶抑制剂PD 98059不影响分化，但可阻断金属硫蛋白的核转运。PI3激酶抑制剂LY 294092和p70S6丝氨酸/苏氨酸激酶抑制剂雷帕霉素可以抑制胰岛素样生长因子- 1诱导的成肌细胞分化，保留细胞质中的金属硫蛋白，降低金属硫蛋白含量。这些结果表明，金属硫蛋白的胞质核易位发生在成肌细胞向肌管分化的早期阶段，并可通过抑制某些信号转导通路而被阻断。金属硫蛋白和锌的短暂核定位可能与分化早期代谢活动对锌的高需求有关。
The changes in subcellular localization of metallothionein during differentiation were studied in two myoblast cell lines, L6 and H9C2. Addition of insulin like growth factor-I or lowering foetal bovine serum to 1% can induce differentiation of myoblasts to myotubes. Metallothionein and zinc were localized mainly in the cytoplasm in myoblasts but were translocated into the nucleus of newly formed myotubes during early differentiation. In fully differentiated myotubes, metallothionein content was decreased with a cytoplasmic localization. Addition of an inhibitor of mitogen-activated protein kinase, PD 98059, did not affect differentiation but blocked nuclear translocation of metallothionein. LY 294092, an inhibitor of PI3 kinase, and rapamycin, an inhibitor of p70S6 serine/threonine kinase, abolished insulin-like growth factor-I induced differentiation of myoblasts, retained metallothionein in the cytoplasm, and decreased metallothionein content. These results demonstrate that the cytoplasmic-nuclear translocation of metallothionein occurs during the early stage of differentiation of myoblasts to myotubes and can be blocked by inhibition of certain signal transduction pathways. The transient nuclear localization of metallothionein and zinc may be related to a high requirement for zinc for metabolic activities during the early stage of differentiation.