Interaction of the macrolide azithromycin with phospholipids. I. Inhibition of lysosomal phospholipase A1 activity

European Journal of Pharmacology
F Van BambekeM P Mingeot-Leclercq

Abstract

Azithromycin, the first clinically developed dicationic macrolide antibiotic, displays an exceptional accumulation in lysosomes of cultured cells. In fibroblasts incubated with 50 mg/l (66.6 microM), it induces a distinct phospholipidosis as evidenced by biochemical and ultrastructural criteria, which strikingly resembles alterations described previously with gentamicin, a pentacationic aminoglycoside antibiotic which inhibits the lysosomal catabolism of phospholipids. We show that both drugs inhibit, in an equimolar manner, the activity of phospholipase A1 (assayed for phosphatidylcholine, included in negatively charged liposomes), in a way consistent with the model of 'charge neutralization' proposed already for gentamicin (Mingeot-Leclercq et al., 1988, Biochem. Pharmacol. 37, 591). Both drugs bind to negatively charged liposomes. Yet, in spite of this binding, azithromycin does not induce aggregation or fusion of negatively charged vesicles, under conditions in which gentamicin (or spermine, a fully hydrophilic polycation) causes a massive aggregation, and bis(beta-diethylaminoethylether)hexestrol (a dicationic amphiphile) causes fusion. The molecular interactions of azithromycin with acidic phospholipids are further examin...Continue Reading

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Citations

Feb 8, 2006·Cell Biology and Toxicology·J K MorelliP J Ciaccio
Oct 24, 1996·European Journal of Pharmacology·J P MontenezM P Mingeot-Leclercq
Sep 26, 2012·Respiratory Research·H Lennart PerssonJenny Persson
Jan 3, 2012·European Journal of Pharmacology·Krunoslav NujićVesna Eraković Haber
Jun 4, 2011·The International Journal of Biochemistry & Cell Biology·Loïc GuillotAnnick Clement
Mar 19, 2014·Pharmacology & Therapeutics·Michael J ParnhamRobin Vos
Jul 6, 2011·British Journal of Pharmacology·M VrančićV Eraković Haber
Sep 11, 2012·Biochimica Et Biophysica Acta·James A Shayman, Akira Abe
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Nov 2, 2006·The Journal of Toxicological Sciences·Kaori TomizawaIkuo Horii
Sep 19, 2006·FEBS Letters·Nora Anderson, Jürgen Borlak
Nov 25, 2014·The Journal of Antimicrobial Chemotherapy·Venkata Saran SolletiAbdelwahab Omri
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Aug 14, 2001·European Journal of Cell Biology·D TytecaM P Mingeot-Leclercq

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