Chloroquine-induced phospholipid fatty liver. Measurement of drug and lipid concentrations in rat liver lysosomes.
Chloroquine-induced phospholipid fatty liver. Measurement of drug and lipid concentrations in rat liver lysosomes.
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氯喹诱导的磷脂脂肪肝。
DOI：
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发表时间：
1985
影响因子：
4.8
通讯作者：
P. Yazaki
中科院分区：
文献类型：
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作者：
K. Hostetler;M. Reasor;P. Yazaki
建立了一种测定大鼠肝溶酶体中氯喹浓度的方法。它采用3 H2O和[U-14 C]蔗糖测定通过自由流电泳获得的纯化溶酶体的溶酶体内水体积。单次给药后12 h，溶酶体中氯喹的浓度为6.3 mM，24 h时升至16.5 mM。继续给药后，48 h和72 h时溶酶体中氯喹的浓度分别为61和74 mM。达到的氯喹的溶酶体浓度足以阻断溶酶体内磷脂酶A1的活性。在12和24小时，磷脂的溶酶体含量分别比对照增加1.7倍和2.6倍。在72小时，溶酶体磷脂是对照的3.7倍。氯喹给药后溶酶体表面负电荷增加，部分原因是溶酶体膜中酸性磷脂与中性磷脂的比例增加。磷脂酰肌醇含量的溶酶体迅速上升与氯喹治疗，并解释了早期增加的比例。双（单酰基甘油）磷酸，一种酸性磷脂只在溶酶体中合成，增加后在氯喹治疗过程中，并占酸性磷脂的持续增加。
A method has been developed to measure the concentration of chloroquine in lysosomes isolated from the liver of rats. It employs 3H2O and [U-14C]sucrose to determine the intralysosomal water volume of purified lysosomes obtained by free flow electrophoresis. Twelve h after a single dose, the concentration of chloroquine in lysosomes was 6.3 mM and at 24 h it rose to 16.5 mM. With continued treatment, lysosomal chloroquine concentrations were 61 and 74 mM at 48 and 72 h. The lysosomal concentrations of chloroquine attained were sufficient to block intralysosomal phospholipase A1 activity. The lysosomal content of phospholipid rises 1.7-fold and 2.6-fold over that of control at 12 and 24 h, respectively. At 72 h, lysosomal phospholipid was 3.7-fold greater than that of control. Lysosomes show an increased negative surface charge with chloroquine administration which is due in part to an increased ratio of acidic to neutral phospholipids in the lysosomal membrane. The phosphatidylinositol content of lysosomes rose rapidly with chloroquine treatment and accounted for the early increase in the ratio. Bis(monoacylglycero)phosphate, an acidic phospholipid synthesized only in lysosomes, increased later in the course of chloroquine treatment and accounted for the continued increase in acidic phospholipids.