氨基糖苷类抗生素对神经磷脂酶D活性的抑制作用。
Inhibition of neural phospholipase D activity by aminoglycoside antibiotics.
作者信息
Liscovitch M, Chalifa V, Danin M, Eli Y
机构信息
Department of Hormone Research, Weizmann Institute of Science, Rehovot, Israel.
出版信息
Biochem J. 1991 Oct 1;279 ( Pt 1)(Pt 1):319-21. doi: 10.1042/bj2790319.
Abstract
The effects of aminoglycoside antibiotics on phospholipase D (PLD) activity were investigated in permeabilized NG108-15 cells and in isolated rat brain membranes. Neomycin inhibited guanosine 5'-[gamma-thio]triphosphate-stimulated PLD activity in digitonin-permeabilized NG108-15 cells in a concentration-dependent manner (50% inhibition at 100 microM). Neomycin similarly inhibited PLD activity present in rat brain membranes and assayed in vitro with [3H]phosphatidylcholine as substrate (50% inhibition at 65 microM). Other aminoglycosides tested (kanamycin, geneticin and streptomycin) were nearly equipotent inhibitors of rat brain PLD. These results indicate that aminoglycoside antibiotics inhibit phosphatidylcholine-PLD activity with comparable and sometimes greater potency than their well known inhibition of phosphoinositide-phospholipase C. The possibility that PLD inhibition could mediate some of the toxic side effects of aminoglycosides is suggested.
摘要
在透化的NG108-15细胞和分离的大鼠脑膜中研究了氨基糖苷类抗生素对磷脂酶D（PLD）活性的影响。新霉素以浓度依赖的方式抑制洋地黄皂苷透化的NG108-15细胞中鸟苷5'-[γ-硫代]三磷酸刺激的PLD活性（100μM时抑制50%）。新霉素同样抑制大鼠脑膜中存在的PLD活性，并以[3H]磷脂酰胆碱为底物进行体外测定（65μM时抑制50%）。测试的其他氨基糖苷类抗生素（卡那霉素、庆大霉素和链霉素）对大鼠脑PLD的抑制作用几乎相当。这些结果表明，氨基糖苷类抗生素抑制磷脂酰胆碱-PLD活性的效力与其对磷酸肌醇-磷脂酶C的抑制作用相当，有时甚至更强。这提示PLD抑制可能介导了氨基糖苷类抗生素的一些毒副作用。
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