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分化诱导剂抗性HL-60细胞的唾液酸化不足

Hyposialylation of differentiation-inducer-resistant HL-60 cells.

作者信息

Gallagher R E, Giangiulio D A, Chang C S, Glover C J, Felsted R L

出版信息

Blood. 1986 Dec;68(6):1402-6.

PMID:3779103
Abstract

The total sialic acid concent of retinoic acid (RA)-resistant or 6-thioguanine (6TG)-resistant HL-60 cells was more than tenfold lower and of dimethylsulfoxide (DMSO)-resistant HL-60 cells was approximately twofold lower than that of parental, wild-type (wt) HL-60 cells. Neuraminidase-inaccessible, ie residual cell-associated sialic acid after neuraminidase treatment, was four- to twelvefold lower in the three differentiation-inducer-resistant sublines than in the parent line. Neuraminidase treatment of 125I-labeled surface membrane glycoproteins (SMGs) from wt HL-60 cells converted the two-dimensional gel electrophoretic pattern to one having features in common with RA- and 6TG-resistant cells. However, neuraminidase treatment did not alter the sensitivity of wt HL-60 cells to differentiation induction by RA, hypoxanthine (purine base), or DMSO. These results indicate that differences in peripheral, neuraminidase-accessible sialic acids are important determinants of the gel electrophoretic mobility of the SMGs of the HL-60 line and sublines but are not likely related to the differentiation-resistance mechanism. Further studies are required to determine if hyposialylation of cryptic, neuraminidase-inaccessible sites has functional significance.

摘要

维甲酸(RA)耐药或6-硫鸟嘌呤(6TG)耐药的HL-60细胞的总唾液酸浓度比亲代野生型(wt)HL-60细胞低十余倍,而二甲基亚砜(DMSO)耐药的HL-60细胞的总唾液酸浓度比亲代细胞低约两倍。神经氨酸酶不可接近的,即神经氨酸酶处理后残留的细胞相关唾液酸,在这三个分化诱导剂耐药亚系中比亲代细胞低4至12倍。用神经氨酸酶处理wt HL-60细胞的125I标记表面膜糖蛋白(SMG),可将二维凝胶电泳图谱转变为具有与RA和6TG耐药细胞共同特征的图谱。然而,神经氨酸酶处理并未改变wt HL-60细胞对RA、次黄嘌呤(嘌呤碱)或DMSO诱导分化的敏感性。这些结果表明,外周神经氨酸酶可接近的唾液酸差异是HL-60细胞系及其亚系SMG凝胶电泳迁移率的重要决定因素,但不太可能与分化耐药机制相关。需要进一步研究以确定隐蔽的、神经氨酸酶不可接近位点的低唾液酸化是否具有功能意义。

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