The effect of lysosomotropic detergents on the permeability properties of the lysosome membrane

• Published in: Biochimica et biophysica acta Vol. 924; no. 3; pp. 452 - 457
• Main Authors: Forster, Susan, Scarlett, Lynne, Lloyd, John B.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 22.06.1987; Elsevier; North-Holland
• Subjects: Ageing, cell death; alpha-Glucosidases - metabolism; Animals; Biological and medical sciences; Cell physiology; Cystine - metabolism; Cystinosis - metabolism; Detergents - pharmacology; Fibroblast, Lysosome; Fibroblasts - metabolism; Fundamental and applied biological sciences. Psychology; Humans; Imidazoles - pharmacology; In Vitro Techniques; Intracellular Membranes - drug effects; L-Lactate Dehydrogenase - metabolism; Liver - drug effects; Lysosomes - drug effects; Lysosomes - enzymology; Lysosomotropic detergent; Membrane permeability; Molecular and cellular biology; Morpholines - pharmacology; Permeability; Rats; Surface-Active Agents - pharmacology; Lysosomotropic detergent; Membrane permeability; Fibroblast, Lysosome; Cell culture; Detergent; Lysosome; Cytotoxicity; Membrane; Permeability; Fibroblast
• ISSN: 0304-4165; 0006-3002; 1872-8006
• DOI: 10.1016/0304-4165(87)90160-7

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 α-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 μg per ml) caused lactate dehydrogenase release from cystinotic fibroblasts, but marginally toxic concentrations failed to induced 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.