INACTIVATION OF LYSOSOMAL FUNCTION IN NORMAL CULTURED HUMAN FIBROBLASTS BY CHLOROQUINE
INACTIVATION OF LYSOSOMAL FUNCTION IN NORMAL CULTURED HUMAN FIBROBLASTS BY CHLOROQUINE
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DOI：
10.1016/0006-2952(73)90197-4
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发表时间：
1973-01-01
影响因子：
5.8
通讯作者：
SCHOFIELD, B
中科院分区：
文献类型：
--
作者：
LIE, SO;SCHOFIELD, B
在正常培养的活的人成纤维细胞中，粘多糖降解的溶酶体功能可以被特异性抑制，而不影响整体细胞活力或生长。在早期的报告中，我们已经表明，介质pH值的增加将逐渐抑制这一功能。本论文证明，浓度约为1-2 × 10− 5 M的氯喹强烈干扰活细胞中的粘多糖降解。电子显微镜显示，在暴露于药物不到2天后，这些细胞中出现类似溶酶体贮积病的形态学图片。我们认为，氯喹的抗疟作用（初步结果将包括奎纳克林和奎宁）和至少一些主要的副作用的药物是由于相同的基本机制：抑制正常的溶酶体活动在寄生虫以及在人类细胞。
The lysosomal function of mucopolysaccharide degradation in normal cultured, living human fibroblasts can specifically be inhibited without affecting over-all cell viability or growth. In an earlier report we have shown that an increase in medium pH will progressively inhibit this function. The present paper demonstrates that chloroquine in concentrations around 1–2 × 10−5M strongly interferes with mucopolysaccharide degradation in the living cell. Electron microscopy shows that a morphological picture resembling a lysosomal storage disease develops in these cells after less than 2 days exposure to the drug. We propose that the antimalarial effect of chloroquine (and preliminary results would include quinacrine and quinine) and at least some of the major side effects of the drug are due to the same basic mechanism: an inhibition of normal lysosomal activities in the parasite as well as in the human cell.