Hyperactivity of cathepsin B and other lysosomal enzymes in fibroblasts exposed to azithromycin, a dicationic macrolide antibiotic with exceptional tissue accumulation

FEBS Letters

Montenez, Jean-Pierre²  Piret, Jocelyne²  Morlighem, Grégory¹  Van Bambeke, Françoise²  Gerbaux, Cécile²  Tulkens, Paul M.² 

[1] Unité de Génétique Cellulaire, Université Catholique de Louvain, avenue Hippocrate 74, B-1200 Bruxelles, Belgium;Unité de Pharmacologie Cellulaire et Moléculaire, Université Catholique de Louvain, avenue E. Mounier 73.70, B-1200 Bruxelles, Belgium

关键词: Cathepsin B;    Lysosomal phospholipidosis;    Azithromycin;    Gentamicin;    Lysosomal enzyme hyperactivity;   

DOI  :  10.1016/0014-5793(96)00975-1

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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 A₁, 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.

【 授权许可】

Unknown