Gerbaux C, Van Bambeke F, Montenez JP, Piret J, Morlighem G, Tulkens PM
Unite de Pharmacologie Cellulaire et Moleculaire, Universite Catholique de Louvain, Bruxelles, Belgium. gerbaux@facm.ucl.ac.be
Azithromycin accumulates in lysosomes where it causes phospholipidosis.
In homogenates prepared by sonication of fibroblasts incubated for 3 days
with azithromycin (66 microM), the activities of sulfatase A, phospholipase
A1, N-acetyl-beta-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 Vmax but not the Km, 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 indirect relation to the lysosomal phospholipidosis.
PMID: 8830663, UI: 96427276