Nitta Kazuo, Kawano Tasuku, Sugawara Shigeki, Hosono Masahiro
Division of Cell Recognition Study, Institute of Molecular Biomembrane and Glycobiology, Tohoku Pharmaceutical University, Sendai, Japan.
Yakugaku Zasshi. 2007 Apr;127(4):553-61. doi: 10.1248/yakushi.127.553.
Silurus asotus (catfish) egg lectin (SAL) has potent affinity to Gal alpha-linked carbohydrate chains of not only glycoproteins but also glycosphingolipids such as globotriaosylceramide (Gb3). SAL selectively bound to Gb3 localized in glycosphingolipid-enriched microdomain (GEM) of Gb3-expressing (Gb3(+)) Burkitt's lymphoma cells. Since treatment of Gb3(+) cells with SAL caused an increase in externalization of phosphatidylserine via activation of P-glycoprotein, and apoptotic volume decrease via activation of G-protein activated K(+) channel-1, SAL may function as an inducer of early apoptotic signal; however, neither caspase-8 and -3 activation nor DNA fragmentation was observed. We therefore investigated whether cell proliferation and viability were altered in SAL-treated Raji cells. SAL caused reduction of Raji cell proliferation without cytotoxicity. Although SAL did not induce apoptotic cell death to Gb3-expressing cells, it functionally behaved as a regulator of cell proliferation. SAL activated the suppression system of cell proliferation, such as down-regulation of c-myc and cdk4, and up-regulation of p21 and p27, inducing G1 arrest of the cell cycle, and consequently inhibited cell proliferation of Raji cells. Therefore, we conclude that SAL leads the cells to early apoptotic status but not late apoptotic (necrotic) status via binding to Gb3 existing in GEM, and that this binding is a prerequisite condition to induce cell cycle stop signal.
鲶鱼卵凝集素（SAL）不仅对糖蛋白的Galα连接碳水化合物链具有强大亲和力，对诸如球三糖神经酰胺（Gb3）等糖鞘脂也有强大亲和力。SAL选择性结合于表达Gb3（Gb3(+)）的伯基特淋巴瘤细胞富含糖鞘脂的微结构域（GEM）中定位的Gb3。由于用SAL处理Gb3(+)细胞会通过激活P-糖蛋白导致磷脂酰丝氨酸外化增加，并通过激活G蛋白激活的K(+)通道-1导致凋亡体积减小，SAL可能作为早期凋亡信号的诱导剂发挥作用；然而，未观察到半胱天冬酶-8和-3的激活或DNA片段化。因此，我们研究了经SAL处理的拉吉细胞中细胞增殖和活力是否发生改变。SAL导致拉吉细胞增殖减少但无细胞毒性。尽管SAL未诱导表达Gb3的细胞发生凋亡性细胞死亡，但它在功能上表现为细胞增殖的调节剂。SAL激活细胞增殖抑制系统，如下调c-myc和cdk4，上调p21和p27，诱导细胞周期的G1期停滞，从而抑制拉吉细胞的细胞增殖。因此，我们得出结论，SAL通过与GEM中存在的Gb3结合使细胞进入早期凋亡状态而非晚期凋亡（坏死）状态，并且这种结合是诱导细胞周期停止信号的先决条件。
