PROTEASE INHIBITORS GENERATE CYTOTOXIC FRAGMENTS FROM ALZHEIMER AMYLOID PROTEIN-PRECURSOR IN CDNA-TRANSFECTED GLIOMA-CELLS

被引：38

作者：

HAYASHI, Y ^{[1
]}

KASHIWAGI, K ^{[1
]}

YOSHIKAWA, K ^{[1
]}

机构：

[1] TOKYO METROPOLITAN INST NEUROSCI, DEPT MOLEC NEUROBIOL, FUCHU, TOKYO 183, JAPAN

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 1992年 / 187卷 / 03期

关键词：

D O I：

10.1016/0006-291X(92)90437-P

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

A human glioma cell line (Bu-17) was stably transfected with full-length cDNA encoding β A4 amyloid protein precursor (APP). When the transfectants were treated with protease inhibitors (leupeptin, E-64, and antipain) and the lysosomotropic agent chloroquine, aberrantly processed fragments of APP having molecular sizes of 8-30kDa were detected with an antibody against the carboxyl-terminal sequence of APP. Immunocytochemistry revealed that these fragments were localized in the lysosome-like organelles. Treatment of the APP cDNA transfectants with chloroquine for 3 days caused cellular degeneration, and leupeptin and E-64 enhanced chloroquine-induced cytotoxicity. These results suggest that inhibition of lysosomal hydrolases impairs intracellular APP metabolism to generate aberrantly processed fragments that induce cytotoxicity. © 1992.

引用

页码：1249 / 1255

页数：7

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