HYPERACTIVITY OF CATHEPSIN-B AND OTHER LYSOSOMAL-ENZYMES IN FIBROBLASTS EXPOSED TO AZITHROMYCIN, A DICATIONIC MACROLIDE ANTIBIOTIC WITH EXCEPTIONAL TISSUE ACCUMULATION
C. Gerbaux et al., HYPERACTIVITY OF CATHEPSIN-B AND OTHER LYSOSOMAL-ENZYMES IN FIBROBLASTS EXPOSED TO AZITHROMYCIN, A DICATIONIC MACROLIDE ANTIBIOTIC WITH EXCEPTIONAL TISSUE ACCUMULATION, FEBS letters, 394(3), 1996, pp. 307-310
Azithromycin accumulates in lysosomes where it causes phospholipidosis
. In homogenates prepared by sonication of fibroblasts incubated for 3
days with azithromycin (66 mu M), the activities of sulfatase A, phos
pholipase A(1), 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 azit
hromycin is non-reversible upon drug withdrawal, prevented by coincuba
tion with cycloheximide, affects the V-max but not the K-m, and is not
reproduced with gentamicin, another drug also causing lysosomal phosp
holipidosis. The data therefore suggest that azithromycin increases th
e level of lysosomal enzymes by a mechanism distinct from the stimulat
ion of gene expression but requiring protein synthesis, and is not in
direct relation to the lysosomal phospholipidosis.