Numazawa S, Honma Y, Yamamoto T, Yoshida T, Kuroiwa Y
Department of Biochemical Toxicology, School of Pharmaceutical Sciences, Showa University, Tokyo, Japan.
Leuk Res. 1995 Dec;19(12):945-53. doi: 10.1016/0145-2126(95)00081-x.
A Na+,K(+)-ATPase inhibitor, bufalin, has been shown previously to induce leukemia cell differentiation. The presence of a circulating Na+,K(+)-ATPase inhibitor has been proposed in mammals. The aim of this study was to explore an endogenous bufalin-like factor that induces leukemia cell differentiation. We found a fraction, designated as fraction A, obtained from human plasma extract that inhibits the growth of several human-derived leukemia cell lines. The effect of the fraction was retained after protease digestion or heat treatment. Murine leukemia cells and ouabain-resistant cells, which are insensitive to bufalin, appeared to be refractory to fraction A in terms of growth inhibition. Fraction A also induced functional and morphological maturation in THP-1 cells. Fraction A was recognized by anti-bufalin anti-serum and inhibited 3H-bufalin binding to K562 cells. These findings suggest that fraction A shows a similar behavior to that of bufalin on leukemia cells by inhibiting Na+,K(+)-ATPase. We propose that an endogenous Na+,K(+)-ATPase inhibitor in human plasma may play a role in cell differentiation.
一种钠钾-ATP酶抑制剂，蟾毒灵，此前已被证明可诱导白血病细胞分化。哺乳动物体内已有人提出存在循环的钠钾-ATP酶抑制剂。本研究的目的是探索一种能诱导白血病细胞分化的内源性类蟾毒灵因子。我们从人血浆提取物中发现了一个组分，命名为组分A，它能抑制几种人源白血病细胞系的生长。该组分经蛋白酶消化或热处理后仍保留其作用效果。对蟾毒灵不敏感的小鼠白血病细胞和哇巴因耐药细胞，在生长抑制方面似乎对组分A也不敏感。组分A还能诱导THP-1细胞发生功能和形态成熟。组分A能被抗蟾毒灵抗血清识别，并抑制3H-蟾毒灵与K562细胞的结合。这些发现表明，组分A通过抑制钠钾-ATP酶，在白血病细胞上表现出与蟾毒灵相似的作用。我们认为，人血浆中的一种内源性钠钾-ATP酶抑制剂可能在细胞分化中发挥作用。
