Cytotoxicity and effect of glycyl-D-phenylalanine-2-naphthylamide on lysosomes

Michel Jadot, Véronique Biélande, Véronique Beauloye, Simone Wattiaux-De Coninck, Robert Wattiaux

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Glycyl-D-phenylalanine-2-naphthylamide (Gly-D-Phe-2-NNap) is a cytotoxic agent as exemplified by its effect on Vero cells in culture. This effect is inhibited to some extent by nigericin. On the other hand, Gly-D-Phe-2-NNap induces an increase of free activity of N-acetylglucosaminidase when incubated with a mitochondrial fraction of rat liver at pH 7.5. The phenomenom is inhibited by chloroquine, NH4Cl and nigericin, substances that are known to increase the intralysosomal pH. The latency of enzymes located in other subcellular structures - mitochondria, peroxisomes and endoplasmic reticulum - is not affected by Gly-D-Phe-2-NNap. Moreover, that compound does not cause a release of FITC-Dextran present in endosomes. Apparently Gly-D-Phe-2-NNap is a specific lytic agent for lysosomes. It is proposed that the molecule behaves like a lysosomotropic substance that is able to attack the lysosomal membrane from the interior of the organelle. Its cytotoxic properties could be explained by its effect on lysosomes.

Original languageEnglish
Pages (from-to)205-209
Number of pages5
JournalBiochimica et Biophysica Acta - Biomembranes
Issue number2
Publication statusPublished - 1 Dec 1990


  • Cytotoxicity
  • Glycyl-D-phenylalanine-2-naphthylamide
  • Lysosome


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