The effect of lysosomotropic detergents on the permeability properties of the lysosome membrane.
Compounds such as N-dodecylimidazole and N-dodecylmorpholine kill cells in culture. Their cytotoxicity has been attributed to accumulation in lysosomes where protonation confers detergent properties resulting in membrane destabilization. This hypothesis has been tested by examining the ability of N-dodecylimidazole and N-dodecylmorpholine to decrease the latency of alpha-glucosidase in isolated rat liver lysosomes. No effect was observed. Nor was N-dodecylimidazole apparently able to increase the permeability of isolated rat liver lysosomes to L-alanine, as no diminution of the disruptive effect of L-alanine methyl ester was seen. N-Dodecylimidazole (10-20 micrograms per ml) caused lactate dehydrogenase release from cystinotic fibroblasts, but marginally toxic concentrations failed to induce cystine release, as might have been expected if lysosome membrane damage had occurred. It is concluded that the cytotoxic effects of lysosomotropic detergents may be mediated by a non-lysosomal mechanism.
Forster
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S
Scarlett
L
L
Lloyd
J B
JB
D000818:Animals; D003553:Cystine / Q000378:metabolism; D003554:Cystinosis / Q000378:metabolism; D003902:Detergents / Q000494:pharmacology*; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D066298:In Vitro Techniques; D007425:Intracellular Membranes / Q000187:drug effects; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008099:Liver / Q000187:drug effects; D008247:Lysosomes / Q000187:drug effects* / Q000201:enzymology; D009025:Morpholines / Q000494:pharmacology*; D010539:Permeability; D051381:Rats; D013501:Surface-Active Agents / Q000494:pharmacology*; D000520:alpha-Glucosidases / Q000378:metabolism
D003902:Detergents; D007093:Imidazoles; D009025:Morpholines; D013501:Surface-Active Agents; D003553:Cystine; D007770:L-Lactate Dehydrogenase; C034251:4-nitrophenyl-alpha-glucosidase; D000520:alpha-Glucosidases; C002822:1-dodecylimidazole; C052796:N-dodecylmorpholine