Makishima M, Honma Y, Hozumi M, Sampi K, Motoyoshi K, Nagata N, Hattori M
Saitama Cancer Center, Japan.
Exp Hematol. 1993 Jul;21(7):839-45.
Protein kinase activities are involved in cellular proliferation and differentiation, and inhibitors of these activities are useful for studying the mechanisms of induction of differentiation. We found that staurosporine, an inhibitor of protein kinase activities, induced morphological differentiation of human myeloblastic leukemia ML-1 cells along myelomonocytic lineage and also induced functional differentiation (increase in nitroblue tetrazolium-reducing and lysozyme activities) in the cells. Several other protein kinase inhibitors such as 1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride (H-7), sphingosine, N-(6-aminoethyl)-5-chloro-1-naphthalenesulfonamide and 1-(5-chloronaphthalene-1-sulfonyl)-1H-hexahydro-1,4-diazepine hydrochloride (ML-9) did not induce the differentiation of ML-1 cells. Treatment with staurosporine induced formation of granules in ML-1 cells, and the granules showed metachromasia by toluidine blue staining; however, histamine content did not increase. The "metachromatic" ML-1 cells were positive for CD14, indicating that staurosporine induced the differentiation of ML-1 cells into metachromatic monocytes/macrophages, 1 alpha,25-dihydroxyvitamin D3 (VD3) enhanced appearance of metachromatic granules in staurosporine-treated cells. These results suggest that modulation of protein phosphorylation by a staurosporine-sensitive protein kinase(s) may be associated with differentiation of ML-1 leukemia cells.
蛋白激酶活性参与细胞增殖和分化，这些活性的抑制剂对于研究分化诱导机制很有用。我们发现，蛋白激酶活性抑制剂星形孢菌素可诱导人髓性白血病ML-1细胞沿髓单核细胞谱系发生形态分化，还可诱导细胞发生功能分化（硝基蓝四氮唑还原活性和溶菌酶活性增加）。其他几种蛋白激酶抑制剂，如1-（5-异喹啉磺酰基）-2-甲基哌嗪二盐酸盐（H-7）、鞘氨醇、N-（6-氨乙基）-5-氯-1-萘磺酰胺和1-（5-氯萘-1-磺酰基）-1H-六氢-1,4-二氮杂卓盐酸盐（ML-9），均未诱导ML-1细胞分化。用星形孢菌素处理可诱导ML-1细胞形成颗粒，这些颗粒经甲苯胺蓝染色呈异染性；然而，组胺含量并未增加。“异染性”ML-1细胞CD14呈阳性，表明星形孢菌素可诱导ML-1细胞分化为异染性单核细胞/巨噬细胞，1α,25-二羟基维生素D3（VD3）可增强星形孢菌素处理细胞中异染性颗粒的出现。这些结果表明，由星形孢菌素敏感的蛋白激酶调节的蛋白磷酸化可能与ML-1白血病细胞的分化有关。
