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Hyperactivity of cathepsin B and other lysosomal enzymes in fibroblasts exposed to azithromycin, a dicationic macrolide antibiotic with exceptional tissue accumulation
Author(s) -
Gerbaux Cécile,
Van Bambeke Françoise,
Montenez Jean-Pierre,
Piret Jocelyne,
Morlighem Grégory,
Tulkens Paul M.
Publication year - 1996
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(96)00975-1
Subject(s) - phospholipidosis , azithromycin , cycloheximide , cathepsin d , cathepsin b , enzyme , biochemistry , lysosome , chemistry , biology , microbiology and biotechnology , antibiotics , protein biosynthesis , phospholipid , membrane
Azithromycin accumulates in lysosomes where it causes phospholipidosis. In homogenates prepared by sonication of fibroblasts incubated for 3 days with azithromycin (66 μM), the activities of sulfatase A, phospholipase A 1 , N ‐acetyl‐ β ‐hexosaminidase and cathepsin B increased from 180 to 330%, but not those of 3 non‐lysosomal enzymes. The level of cathepsin B mRNA was unaffected. The hyperactivity induced by azithromycin is non‐reversible upon drug withdrawal, prevented by coincubation with cycloheximide, affects the V max but not the K m , and is not reproduced with gentamicin, another drug also causing lysosomal phospholipidosis. The data therefore suggest that azithromycin increases the level of lysosomal enzymes by a mechanism distinct from the stimulation of gene expression but requiring protein synthesis, and is not in direct relation to the lysosomal phospholipidosis.