A selective cholesterol-dependent induction of H+/OH- currents in phospholipid vesicles by amphotericin B.

A selective cholesterol-dependent induction of H+/OH- currents in phospholipid vesicles by amphotericin B.
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两性霉素 B 选择性胆固醇依赖性诱导磷脂囊泡中的 H/OH-电流。

DOI:
10.1021/bi00408a004
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发表时间:
1988
期刊:
影响因子:
2.9
通讯作者:
Cafiso,DS
Cafiso,DS
中科院分区:
生物学3区
文献类型:
--
作者:
Hartsel,SC;Perkins,WR;McGarvey,GJ;Cafiso,DS

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S. C. Hartsel,1 W. R. Perkins,§ GJ McGarvey,and D. S. Cafiso ** Department of Chemistry,University of Virginia,Charlottesville,Virginia 22901 Received January 13,1988; Revised Mandarin pt Received February 23,1988摘要:通过使用电位依赖性顺磁探针研究了异甘草素B对小单层囊泡的质子/氢氧化物渗透性的影响。两性霉素B在1 - 10摩尔/囊泡时,使卵磷脂酰胆碱(卵PC)囊泡的背景H +/OH-渗透性适度增加4 - 8倍。然而,在胆固醇的存在下,阿朴霉素B促进H +/OH-渗透性的显著增加超过2个数量级。令人惊讶的是,这在含有麦角固醇的囊泡膜中没有观察到。在由5 - 15 mol %麦角固醇组成的膜中,阿替霉素B在促进H +/OH~电流方面甚至不如在纯卵PC囊泡中有效。在由鸡蛋PC和鸡蛋PC加胆固醇或麦角固醇形成的囊泡中,测量了由阿氏菌素B促进的K+电流。没有发现显着的甾醇依赖性的K+电流。这些结果有力地表明,不同的机制,或异黄酮B/甾醇复合物,负责诱导H +/OH-和K+电流。这些结果对于理解阿替霉素B的治疗和毒性作用具有重要意义。
S. C. Hartsel, 1 W. R. Perkins, § GJ McGarvey, and D. S. Cafiso** Department of Chemistry, University of Virginia, Charlottesville, Virginia 22901 Received January 13, 1988; Revised Manuscript Received February 23, 1988 abstract: The effect of amphotericin B on the proton/hydroxide permeability of small unilamellar vesicles has been investigated by using potential-dependent paramagnetic probes. Amphotericin B at 1-10 mole-cules/vesicle causes a modest 4-8-fold increase in the background H+/OH" permeability of egg phos-phatidylcholine (egg PC) vesicles. However, in the presence of cholesterol, amphotericin B promotes a dramatic increase in the H+/OH" permeability of more than 2 orders of magnitude. Surprisingly, this is not observed in vesicle membranes containing ergosterol. In membranes composed of 5-15 mol% ergosterol, amphotericin B is even less effective at promoting H+/OH~ currents than in pure egg PC vesicles. The K+ current promoted by amphotericin B in vesicles formed from egg PC and from egg PC plus cholesterol or ergosterol was measured. No significant sterol dependence was found for the K+ current. These results strongly suggest that different mechanisms, or amphotericin B/sterol complexes, are responsible for the induction of H+/OH" and K+ currents. These results have important implications for understandingthe therapeutic and toxic effects of amphotericin B.
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