Endocytosis by liver cells during suppression of intralysosomal proteolysis.
The lysosomotropic agent chloroquine is widely used as a specific inhibitor of intralysosomal proteolysis in isolated hepatocytes. It was shown that in vitro chloroquine reversibly inhibited purified cathepsins H, B, L in concentrations less than those observed inside lysosomes in vivo. However, administration of high doses of chloroquine to rats (30-50 mg/kg i.p. as a single or repeated injections) was followed by increased cathepsin D and cysteine proteinase activities, as well as other lysosomal enzymes. Chloroquine administration did not induce any changes of carbon particles phagocytosis by liver cells (macrophages); modifications of fluid-phase (125I-PVP uptake) and receptor-mediated endocytosis (125I-asialo-fetuin uptake) were noted. Chloroquine administered in vivo reproduced some symptoms of lysosomal storage diseases (especially during repeated drug administration).
Korolenko
T A
TA
Institute of Physiology, Academy of Medical Sciences of USSR, Novosibirsk.
Rukavishnikova
E V
EV
Safina
A F
AF
Dushkin
M I
MI
Mynkina
G I
GI
D000818:Animals; D002401:Cathepsin B / Q000378:metabolism; D056655:Cathepsin H; D056668:Cathepsin L; D002403:Cathepsins / Q000378:metabolism; D002738:Chloroquine / Q000494:pharmacology; D003546:Cysteine Endopeptidases; D004705:Endocytosis / Q000187:drug effects / Q000502:physiology*; D010450:Endopeptidases; D006868:Hydrolysis; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008247:Lysosomes / Q000187:drug effects / Q000502:physiology*; D008264:Macrophages / Q000187:drug effects; D008297:Male; D010587:Phagocytosis / Q000187:drug effects; D011092:Polyethylene Glycols / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D011092:Polyethylene Glycols; D002738:Chloroquine; D002403:Cathepsins; D010450:Endopeptidases; D003546:Cysteine Endopeptidases; D002401:Cathepsin B; D056668:Cathepsin L; C534280:Ctsl protein, rat; D056655:Cathepsin H; C534128:Ctsh protein, rat; C016811:tyloxapol