Secondary mutation resistant to 7-ketocholesterol rescues a sterol metabolic defect in amphotericin B-resistant Chinese hamster cell line.

M Kuwano, A Masuda, K Hidaka, S I Akiyama
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引用次数: 5

Abstract

Amphotericin B-resistant mutants isolated from Chinese hamster V79 cells (1) are defective in cholesterol synthesis and more sensitive to an oxygenated sterol analog, 7-ketocholesterol, than their parental cell line. We isolated 7-ketocholesterol-resistant mutants from an amphotericin B-resistant mutant, AMBR-1. The 7-ketocholesterol-resistant mutants had regained increased level of free cholesterol, and they showed somewhat similar dose-response curves to amphotericin B as that of V79. Sterol synthesis from acetate, but not from mevalonate, in 7-ketocholesterol-resistant clones was threefold higher than that of AMBR-1. 7-Ketocholesterol-resistant clone, unlike AMBR-1, could form colonies in the presence of lipoprotein-depleted serum. The results are discussed in terms of probable change in the sterol biosynthetic pathway by the different lesions.

7-酮胆固醇抗性继发突变修复了两性霉素b抗性中国仓鼠细胞系的一种固醇代谢缺陷。
从中国仓鼠V79细胞中分离出的两性霉素b抗性突变体(1)在胆固醇合成方面存在缺陷,并且比亲代细胞系对含氧固醇类似物7-酮胆固醇更敏感。我们从两性霉素b抗性突变体AMBR-1中分离出7-酮胆固醇抗性突变体。7-酮胆固醇抗性突变体恢复了增加的游离胆固醇水平,并且它们对两性霉素B的剂量-反应曲线与V79相似。在7-酮胆固醇抗性无性系中,由醋酸酯合成甾醇比AMBR-1高3倍,而不是由甲羟戊酸合成。7-酮胆固醇抵抗克隆,不像AMBR-1,可以在脂蛋白耗尽的血清中形成菌落。结果讨论了可能的变化在甾醇生物合成途径由不同的病变。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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