Disruptive Effect of Chloroquine on Lysosomes in Cultured Rat Hepatocytes(Biochemistry/Molecular Biology)
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概要
- 論文の詳細を見る
Chloroquine has been used as an anti-malarial drug and is known as a lysosomotropic amine as well. The effects of chloroquine on lysosomal integrity in cultured rat hepatocytes were studied by measuring lysosomal enzyme β-glucuronidase (β-G) or lysosomal membrane glycoprotein (lamp-1) in Percoll density gradient fractions, in the cytosolic fraction obtained from cells permeabilized by digitonin or in the cytosolic fraction obtained by conventional cell fractionation. The distribution of β-G on a Percoll density gradient in chloroquine-treated cells was approximately similar to that of a cytosolic protein, mevalonate pyrophosphate decarboxylase, in nontreated cells. Lamp-1 was decreased in the lysosomal fractions on a Percoll density gradient in chloroquine-treated cells, and was increased in the plasma membrane fraction, as compared with the levels in nontreated cells. Furthermore, after cells were cultured in the presence and absence of chloroquine, the proportions of β-G activity in the cytosolic fraction obtained from the digitonin-permeabilized cells were 19% and 4%, while those in the cytosolic fraction obtained by conventional cell fractionation were 54% and 26%, respectively. From these findings, we infer that chloroquine caused the disruption of lysosomes in the living cells, and that lysosomes treated with chloroquine were easily disrupted by homogenization or centrifugation during cell fractionation.
- 公益社団法人日本薬学会の論文
- 2005-06-01
著者
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MICHIHARA Akihiro
Faculty of Pharmacy and Pharmaceutical Sciences, Fukuyama University
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AKASAKI Kenji
Faculty of Pharmacy and Pharmaceutical Sciences, Fukuyama University
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TSUJI Hiroshi
Faculty of Pharmacy and Pharmaceutical Sciences, Fukuyama University
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MIURA AYAKO
WHO Collaborating Center for Research on Primary Prevention of Cardiovascular Diseases
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Miura Ayako
京都府立医科大学 法医学
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Akasaki K
Fac. Of Pharmacy And Pharmaceutical Sciences Fukuyama Univ.
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Akasaki Kenji
Faculty Of Pharmacy & Pharmaceutical Sciences Of Fukuyama University
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Tsuji H
Faculty Of Pharmacy And Pharmaceutical Sciences Fukuyama University
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Tsuji Hiroshi
Faculty Of Pharmacy And Pharmaceutical Sciences Fukuyama University
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Akasaki K
Faculty Of Pharmacy And Pharmaceutical Sciences Fukuyama University
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Toda Ken
Faculty of Pharmacy and Pharmaceutical Sciences, Fukuyama University
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Kubo Takuo
Faculty of Pharmacy and Pharmaceutical Sciences, Fukuyama University
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FUJIWARA Yoshiteru
Faculty of Pharmacy and Pharmaceutical Sciences, Fukuyama University
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Miura Ayako
Department Of Environmental Preservation And Development
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Toda Ken
Faculty Of Pharmacy And Pharmaceutical Sciences Fukuyama University
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Kubo Takuo
Faculty Of Pharmacy And Pharmaceutical Sciences Fukuyama University
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Fujiwara Yoshiteru
Faculty Of Pharmacy And Pharmaceutical Sciences Gakuencho Fukuyama University
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Tsuji Hiroshi
Faculty Of Pharmacy & Pharmaceutical Sciences Of Fukuyama University
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