Phospholipase C activation by anesthetics decreases membrane-cytoskeleton adhesion.

Phospholipase C activation by anesthetics decreases membrane-cytoskeleton adhesion.
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麻醉剂激活磷脂酶 C 会降低膜-细胞骨架粘附。

DOI:
--
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发表时间:
2001
影响因子:
4
通讯作者:
Michael P. Sheetz
Michael P. Sheetz
中科院分区:
生物学2区
文献类型:
--
作者:
D. Raucher;Michael P. Sheetz

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许多不同的两亲性化合物引起细胞的液相内吞速率增加,同时膜-细胞骨架粘附减少。然而,这些化合物并不具有共同的化学结构,这使得机制甚至作用部位都是未知的。一种可能的作用机制是通过修饰质膜双层的细胞质表面来改变肌醇脂质代谢。通过比较可渗透的两亲性胺用作局部麻醉剂与其不可渗透的类似物,我们发现,进入细胞质表面是必要的,以增加内吞率和降低膜-细胞骨架粘附。与此同时,我们发现,只有渗透性胺才能降低质膜中磷脂酰肌醇4,5-二磷酸(PIP(2))的水平,增加细胞质Ca(2+)。细胞膜PIP(2)的降低和Ca(2+)的升高与细胞膜-细胞膜粘附力的降低相一致。肌醇标记显示,渗透性麻醉剂增加了磷脂酰肌醇-4-磷酸水平,表明脂质周转增加。与以前的观察结果一致,磷脂酶C(PLC)抑制剂阻断麻醉剂对PIP(2)和细胞质Ca(2+)水平的影响,以及粘附力的下降。因此,我们认为,PLC活性增加胺麻醉剂在质膜的细胞质表面,从而导致膜细胞骨架粘附减少。
Many different amphiphilic compounds cause an increase in the fluid-phase endocytosis rates of cells in parallel with a decrease in membrane-cytoskeleton adhesion. These compounds, however, do not share a common chemical structure, which leaves the mechanism and even site of action unknown. One possible mechanism of action is through an alteration of inositol lipid metabolism by modifying the cytoplasmic surface of the plasma membrane bilayer. By comparing permeable amphiphilic amines used as local anesthetics with their impermeable analogs, we find that access to the cytoplasmic surface is necessary to increase endocytosis rate and decrease membrane-cytoskeleton adhesion. In parallel, we find that the level of phosphatidylinositol 4,5-bisphosphate (PIP(2)) in the plasma membrane is decreased and cytoplasmic Ca(2+) is increased only by permeable amines. The time course of both the decrease in plasma membrane PIP(2) and the rise in Ca(2+) parallels the decrease in cytoskeleton-membrane adhesion. Inositol labeling shows that phosphatidylinositol-4-phosphate levels are increased by the permeable anesthetics, indicating that lipid turnover is increased. Consistent with previous observations, phospholipase C (PLC) inhibitors block anesthetic effects on the PIP(2) and cytoplasmic Ca(2+) levels, as well as the drop in adhesion. Therefore, we suggest that PLC activity is increased by amine anesthetics at the cytoplasmic surface of the plasma membrane, which results in a decrease in membrane-cytoskeleton adhesion.
DOI: 10.1091/mbc.11.12.4339
发表时间: 2000-12-01
影响因子: 3.3
作者:
Togo, T;Krasieva, TB;Steinhardt, RA
通讯作者: Steinhardt, RA
DOI: 10.1016/s0021-9258(19)49643-9
发表时间: 1992-07
期刊: The Journal of biological chemistry
影响因子: --
作者:
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通讯作者: D. Yule;J. Williams
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DOI: 10.1021/bi00166a006
发表时间: 1992
期刊: Biochemistry
影响因子: 2.9
作者:
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