Takano T, Takada K, Tada H, Nishiyama S, Amino N
Department of Laboratory Medicine, Osaka University Medical School, Japan.
J Endocrinol. 1994 Nov;143(2):221-6. doi: 10.1677/joe.0.1430221.
Long-term administration of lithium is one of the well-known causes of goiter. It can stimulate DNA synthesis in rat thyroid cells (FRTL-5) treated with thyroid-stimulating hormone (TSH). To investigate the mitogenic signal transduction system activated by lithium, lithium-induced DNA synthesis and Ca2+ influx were studied using two protein kinase inhibitors, genistein as a specific tyrosine kinase inhibitor and staurosporine as a potent inhibitor of protein kinase C. Genistein but not staurosporine blocked the DNA synthesis induced by lithium in TSH-primed cells but neither compound had any effect on the Ca2+ entry stimulated by lithium. Genistein clearly attenuated the phosphotyrosine content of the 175 kDa substrate in the presence of lithium but staurosporine failed to do so. Moreover, lithium could also stimulate DNA synthesis in protein kinase C down-regulated cells. These data demonstrate that lithium may require the activation of a particular genistein-sensitive kinase, possibly a tyrosine kinase, to induce cell proliferation. It is suggested that the phorbol ester-sensitive protein kinase C family might not participate in the mitogenic signal transduction pathway activated by lithium.
长期服用锂盐是导致甲状腺肿大的常见原因之一。它能刺激经促甲状腺激素（TSH）处理的大鼠甲状腺细胞（FRTL-5）中的DNA合成。为了研究锂激活的促有丝分裂信号转导系统，我们使用两种蛋白激酶抑制剂，即作为特异性酪氨酸激酶抑制剂的染料木黄酮和作为蛋白激酶C强效抑制剂的星形孢菌素，来研究锂诱导的DNA合成和Ca2+内流。染料木黄酮而非星形孢菌素可阻断TSH预处理细胞中锂诱导的DNA合成，但两种化合物对锂刺激的Ca2+内流均无影响。在有锂存在的情况下，染料木黄酮明显降低了175 kDa底物的磷酸酪氨酸含量，但星形孢菌素未能做到这一点。此外，锂还能刺激蛋白激酶C下调的细胞中的DNA合成。这些数据表明，锂可能需要激活一种特定的对染料木黄酮敏感的激酶，可能是一种酪氨酸激酶，来诱导细胞增殖。提示佛波酯敏感的蛋白激酶C家族可能不参与锂激活的促有丝分裂信号转导途径。
