GDP-fucose:GM1 alpha 1----2fucosyltransferase is activated in parenchymal cells of rat liver during early stages of N-2-acetylaminofluorene induced hepatocarcinogenesis.

GDP-fucose:GM1 alpha 1----2fucosyltransferase is activated in parenchymal cells of rat liver during early stages of N-2-acetylaminofluorene induced hepatocarcinogenesis.
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GDP-岩藻糖:GM1 α 1----2岩藻糖基转移酶在 N-2-乙酰氨基芴诱导的肝癌发生的早期阶段在大鼠肝实质细胞中被激活。

DOI:
10.1093/carcin/11.1.89
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发表时间:
1990
期刊:
影响因子:
4.7
通讯作者:
Holmes,EH
Holmes,EH
中科院分区:
医学2区
文献类型:
--
作者:
Holmes,EH

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从已喂食正常饮食或添加 0.03%N-2-乙酰氨基芴 (AAF) 的饮食 4 周的 Fischer 344 大鼠中分离出来自肝实质和非实质细胞的神经节苷脂。来自肝细胞级分的神经节苷脂的特征在于,在 AAF 喂养的动物的实质细胞中诱导 II3NeuAcIV3αGalIV2FucGg4 和 GM3 合成,而在正常饮食喂养的动物的实质细胞中则缺失这些合成。此外,在 AAF 喂养的动物的细胞部分中观察到了与 GM1 和 GD1 相对应的新条带。发现 AAF 喂养后诱导的 GM1 特异性 α1→2 岩藻糖基转移酶活性在 AAF 喂养动物的实质细胞部分中富集 5 至 6 倍,并与这些细胞部分中的实质细胞标记酶葡萄糖 6-磷酸酶相关。在饮食中给动物喂食 1.87% 的肝毒素对乙酰氨基酚 10 周后,α1→2 岩藻糖基转移酶的水平没有增加。生产了 II3NeuAcIV3αGalIV2FucGg4 特异性抗体并用于组织定位研究。这些结果表明正常肝组织很少或没有染色,或者观察到喂食对乙酰氨基酚后的染色。相比之下,饲喂 0.03% AAF 3 周后,动物肝组织的局部染色区域非常明显。这些结果表明,α1-2岩藻糖基转移酶和岩藻神经节苷脂合成的诱导很可能是肝实质细胞的特性,并且与 AAF 诱导的癌发生早期阶段发生的事件有关。
Gangliosides from liver parenchymal and non-parenchymal cells were isolated from Fischer 344 rats that had been fed normal diet or a diet supplemented with 0.03%N-2-acetylaminofluorene (AAF) for 4 weeks. Gangliosides from liver cell fractions were characterized by an induction of both II3NeuAcIV3αGalIV2FucGg4and GM3synthesis in the parenchymal cells of AAF-fed animals which were missing in parenchymal cells from animals fed normal diet. In addition, new bands corresponding to GM1and GD1awere observed in cell fractions of AAF-fed animals. The activity of the GM1-specific α1→2fucosyltransferase induced after AAF feeding was found to be enriched 5- to 6-fold in the parenchymal cell fraction of AAF-fed animals and correlated with the parenchymal cell marker enzyme glucose 6-phosphatase in these cell fractions. Feeding animals the hepatotoxin acetaininophen at 1.87% in the diet for 10 weeks resulted in no increase in the levels of the α1→2fucosyltrans-ferase. Antibodies specific for II3NeuAcIV3αGalIV2FucGg4were produced and utilized in tissue localization studies. These results indicated little or no staining of normal liver tissue or that after acetaminophen feeding was observed. In contrast, focal areas of staining of liver tissue from animals after 3 weeks of 0.03% AAF feeding were readily apparent. These results indicate that induction of α1–2fucosyltransferase and fucoganglioside synthesis is most probably a property of liver parenchymal cells and is associ ated with events occurring during early stages of AAF-induced carcinogenesis.