Tada H, Takada K, Amino N, Miyai K
Department of Laboratory Medicine, Osaka University School of Medicine, Japan.
Biochem Biophys Res Commun. 1991 May 31;177(1):17-21. doi: 10.1016/0006-291x(91)91941-5.
IGF-I, when added to the TSH-primed FRTL-5 cells, induces a long lasting Ca2+ influx, and then, DNA synthesis. Moreover, Ca2+ channel agonist, B AY K8644 can mimic these effects on cell proliferation. We studied the effect of HMG-CoA reductase inhibitor, Pravastatin on IGF-I-induced cell cycle progression in FRTL-5 cells. Pravastatin inhibited DNA synthesis induced both by IGF-I and by BAY K8644. In contrast, Ca2+ influx stimulated by IGF-I was unaffected. These data demonstrate that the signal transduction pathway evoked by IGF-I may possibly involve pravastatin-sensitive process at the downstream step of Ca2+ entry. HMG-CoA reductase inhibitors are known to modulate some cellular signal transduction systems by blocking the membrane attachment of low molecular weight GTP binding proteins such as p21ras. Therefore, pravastatin-sensitive process that we have shown here might possibly involve some of such small G protein.
在促甲状腺激素（TSH）预处理的FRTL-5细胞中加入胰岛素样生长因子-I（IGF-I），可诱导持久的钙离子内流，随后促进DNA合成。此外，钙离子通道激动剂BAY K8644可模拟这些对细胞增殖的作用。我们研究了HMG-CoA还原酶抑制剂普伐他汀对IGF-I诱导FRTL-5细胞周期进程的影响。普伐他汀抑制了IGF-I和BAY K8644诱导的DNA合成。相反，IGF-I刺激的钙离子内流未受影响。这些数据表明，IGF-I引发的信号转导途径可能在钙离子内流的下游步骤涉及普伐他汀敏感的过程。已知HMG-CoA还原酶抑制剂通过阻断低分子量GTP结合蛋白（如p21ras）的膜附着来调节一些细胞信号转导系统。因此，我们在此展示的普伐他汀敏感过程可能涉及某些此类小G蛋白。
