Stimulatory, permeabilizing, and toxic effects of amphotericin B on L cells.
Stimulatory, permeabilizing, and toxic effects of amphotericin B on L cells.
复制标题
两性霉素 B 对 L 细胞的刺激、透化和毒性作用。
DOI：
10.1128/aac.26.6.892
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发表时间：
1984
影响因子：
4.9
通讯作者：
Medoff,G
中科院分区：
文献类型：
--
作者：
Brajtburg,J;Elberg,S;Medoff,J;Kobayashi,GS;Schlessinger,D;Medoff,G
高浓度的两性霉素B(Amb)可杀死小鼠L细胞，但低浓度的Amb可提高细胞的培养效率，并刺激标记的前体进入DNA和RNA。因此，AMB对L细胞有两种不同的作用，刺激作用和毒性作用，并且它们发生在不同的剂量相关阶段。AMB还影响L细胞的通透性。在剂量效应研究中，随着[~3H]尿苷掺入RNA的刺激，细胞膜通透性增加，测量为K+离子的损失。相反，只有在AMB诱导的通透性改变的恢复期细胞才能观察到[~3H]胸腺嘧啶核苷掺入DNA的刺激作用。当培养液中的K+浓度从4.5 mM降至0.5，或在培养液中加入1 mM哇巴因时，细胞杀伤作用增强，但亚毒浓度的AMB的刺激和通透作用不受影响。此外，没有任何渗透作用的多烯类抗生素etruscomycin仍能提高平台率，并使[~3H]尿苷掺入RNA和[~H]胸腺嘧啶核苷掺入DNA。我们的结果表明，AMB的剂量相关的刺激、渗透和毒性作用很可能有不同的作用机制，并且可能相互独立。
High concentrations of amphotericin B (AmB) killed mouse L cells, but low concentrations increased plating efficiency and stimulated the incorporation of labeled precursors into DNA and RNA. Thus, there were two disparate effects of AmB on L cells, stimulatory and toxic, and they occurred in distinct dose-related stages. AmB also affected the permeability of L cells. In dose-response studies, increases in cell membrane permeability, measured as the loss of K+ ions, occurred along with the stimulation of [3H]uridine incorporation into RNA. In contrast, stimulation of [3H]thymidine incorporation into DNA was only observed in cells recuperating from AmB-induced permeability changes. When the K+ concentration in the medium was lowered to 0.5 from 4.5 mM, or when 1 mM ouabain was added to the cultures, cell killing was potentiated, but the stimulatory and permeabilizing effects of subtoxic concentrations of AmB were unaffected. Furthermore, etruscomycin, a polyene antibiotic without any permeabilizing effects, nevertheless induced an enhancement of plating efficiency and of incorporation of [3H]uridine into RNA and [3H]thymidine into DNA. Our results suggest that the dose-related stimulatory, permeabilizing, and toxic effects of AmB most probably have distinct mechanisms of action and may be independent of one another.