Effects of acidotropic compounds on the secretory pathway: inhibition of secretion and processing of the third and fourth components of complement.
Acidotropic compounds (also termed lysosomotropic) such as chloroquine and amantadine interfered with processing of the single-chain precursors to the third and fourth components of complement (C3 and C4) by the human hepatoma-derived cell line HepG2. When these compounds were added to culture medium, the precursors of C3 and C4 became the major secretory forms in contrast to the normal secretion of C3 and C4 as their mature forms. In addition, secretion of C3, C4, and total protein was inhibited by these compounds. Our results indicate that lysosomotropic agents, in addition to their well recognized effects on lysosomes and endosomes, inhibit functions of the secretory pathway.
D000547:Amantadine / Q000494:pharmacology; D001550:Benzamidines / Q000494:pharmacology; D006528:Carcinoma, Hepatocellular / Q000378:metabolism; D002460:Cell Line; D002738:Chloroquine / Q000494:pharmacology; D003176:Complement C3 / Q000378:metabolism*; D003181:Complement C4 / Q000378:metabolism*; D003514:Cyclohexylamines / Q000494:pharmacology; D004591:Electrophoresis, Polyacrylamide Gel; D005021:Ethylamines / Q000494:pharmacology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008113:Liver Neoplasms / Q000378:metabolism; D008247:Lysosomes / Q000187:drug effects; D011498:Protein Precursors / Q000378:metabolism; D011499:Protein Processing, Post-Translational / Q000187:drug effects
D001550:Benzamidines; D003176:Complement C3; D003181:Complement C4; D003514:Cyclohexylamines; D005021:Ethylamines; D011498:Protein Precursors; D002738:Chloroquine; D000547:Amantadine; C032157:benzamidine; C016162:triethylamine