Leupeptin and E-64, inhibitors of cysteine proteinases, prevent gentamicin-induced lysosomal phospholipidosis in cultured rat fibroblasts
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Drug-induced phospholipidosis
2006, FEBS LettersCocaine induces a mixed lysosomal lipidosis in cultured fibroblasts, by inactivation of acid sphingomyelinase and inhibition of phospholipase A1
2004, Toxicology and Applied PharmacologyCitation Excerpt :The rapid recovery of acid sphingomyelinase upon cocaine withdrawal points to a fast turnover of acid sphingomyelinase in the cells. Interestingly, in gentamicin-induced lipid storage disorders, sphingomyelinase activity was also decreased and inhibitors of cysteine proteinases exerted a protective effect (Montenez et al., 1994a,b). Similarly, cell treatment with the antidepressant, desipramine, induced a loss of sphingomyelinase activity that was prevented by leupeptin (Hurwitz et al., 1994).
Leupeptin protects cochlear and vestibular hair cells from gentamicin ototoxicity
2002, Hearing ResearchGentamicin causes endocytosis of Na/Pi cotransporter protein (NaPi-2)
2001, Kidney InternationalCitation Excerpt :Following treatment with a high Pi diet8, 21 and/or parathyroid hormone (PTH)25, 26, NaPi-2 is also endocytosed from the apical BBM and is eventually accumulated in the lysosomes where it is degraded. In the case of gentamicin, however, gentamicin is rapidly targeted to the lysosomes14,27-31 and is an inhibitor of lysosomal enzymes32-38, and therefore, the NaPi-2 protein is accumulated in the lysosomes without degradation. A similar picture is seen when rats are first pretreated with leupeptin, an inhibitor of lysosomal enzymes, and then the rats are fed a high Pi diet and/or infused with PTH, in which the internalized NaPi-2 protein is localized in the lysosomes21,26,39.
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