Protein sialylation by sialyltransferase involves radiation resistance
Protein sialylation by sialyltransferase involves radiation resistance
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DOI：
10.1158/1541-7786.mcr-07-2209
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发表时间：
2008-08-01
影响因子：
5.2
通讯作者：
Lee, Yun-Sil
中科院分区：
文献类型：
--
作者：
Lee, Minyoung;Lee, Hae-June;Lee, Yun-Sil
此前，我们确定 β-半乳糖苷 α(2,6)-唾液酸转移酶 (ST6Gal I) 作为电离辐射的候选生物标志物。 ST6Gal I 的表达和蛋白质唾液酸化水平在辐射暴露后以剂量依赖性方式增加。辐射诱导 ST6Gal I 裂解，并且 ST6Gal I 的裂解形式可溶并分泌。整合素β1（一种糖基化细胞表面蛋白）的唾液酸化受到辐射暴露的刺激，这增加了其稳定性。在最初显示低水平 ST6Gal I 表达的 SW480 结肠癌细胞中 ST6Gal I 的过表达增加了整合素 01 的唾液酸化，也增加了蛋白质的稳定性。通过用神经氨酸酶 2 或神经氨酸酶 3 转染或用靶向 ST6Gal I 的短干扰 RNA 处理来抑制唾液酸化，可逆转 ST6Gal I 过表达的影响。此外，ST6Gal I 过表达增加了辐射暴露后的克隆存活率，并减少了辐射诱导的细胞死亡和 caspase 3 激活。然而，通过神经氨酸酶 2 去除唾液酸或通过靶向 ST6Gal I 的短干扰 RNA 敲低表达，可以恢复辐射诱导的细胞死亡表型。总之，辐射暴露可通过诱导 ST6Gal 1 的表达来增加糖蛋白（如整合素 β 1）的唾液酸化，而蛋白质唾液酸化的增加有助于细胞的辐射抵抗。
Previously, we identified beta-galactoside alpha(2,6)-sialyltransferase (ST6Gal I) as a candidate biomarker for ionizing radiation. The expression of ST6Gal I and the level of protein sialylation increased following radiation exposure in a dose-dependent manner. Radiation induced ST6Gal I cleavage and the cleaved form of ST6Gal I was soluble and secreted. Sialylation of integrin beta 1, a glycosylated cell surface protein, was stimulated by radiation exposure and this increased its stability. Overexpression of ST6Gal I in SW480 colon cancer cells that initially showed a low level of ST6Gal I expression increased the sialylation of integrin 01 and also increased the stability of the protein. Inhibition of sialylation by transfection with neuraminidase 2 or neuraminidase 3 or by treatment with short interfering RNA targeting ST6Gal I reversed the effects of ST6Gal I overexpression. In addition, ST6Gal I overexpression increased clonogenic survival following radiation exposure and reduced radiation-induced cell death and caspase 3 activation. However, removal of sialic acids by neuraminidase 2 or knockdown of expression by short interfering RNA targeting ST6Gal I restored radiation-induced cell death phenotypes. In conclusion, radiation exposure was found to increase the sialylation of glycoproteins such as integrin beta 1 by inducing the expression of ST6Gal 1, and increased protein sialylation contributed to cellular radiation resistance.