[Effect of the segregation and accumulation of chloroquine and daunorubicin by L cells (LSM subline) on the activity of lysosomal hydrolases].
Kinetics of chloroquine and daunorubicin (DNR) uptake by cultured L cells (subline LSM) has been studied. With their constant concentrations in the medium the uptake of both chloroquine and DNR was characterized as a two phase process. Within 1.5-2 hours, these cells accumulated as much as 90 per cent of the total chloroquine and DNR amounts taken up during the whole incubation period. The segregation and accumulation of these substances took place in lysosomes. Chloroquine and DNR concentrations within lysosomes exceed those in the medium by 1100 and 5000 times, respectively. The chloroquine and DNR accumulation in lysosomes inhibited activities of some lysosomal hydrolases tested: cathepsins B and D, N-acetyl-beta, D-glucosaminidase and acid phosphatase. Unlike, the activity of acid lipase was not affected by chloroquine, and was sufficiently stimulated (by 55%) by DNR. The mechanism of inhibition of lysosomal enzymes by chloroquine and DNR is not yet known, although some suggestions are made. Possible consequences of lysosomal activity inhibition for cell metabolism are discussed in addition to a possible role of lysosomotropic agents as regulators of lysosomal functional activity.
Bulychev
A G
AG
Semenova
E G
EG
Assinovskaia
O A
OA
Prozorovskaia
M P
MP
D000818:Animals; D002460:Cell Line; D002738:Chloroquine / Q000032:analysis / Q000493:pharmacokinetics*; D003592:Cytophotometry; D003630:Daunorubicin / Q000032:analysis / Q000493:pharmacokinetics*; D006867:Hydrolases / Q000032:analysis / Q000037:antagonists & inhibitors / Q000378:metabolism*; D007739:L Cells / Q000201:enzymology*; D008247:Lysosomes / Q000201:enzymology*; D051379:Mice; D013050:Spectrometry, Fluorescence; D013997:Time Factors
D002738:Chloroquine; D006867:Hydrolases; D003630:Daunorubicin
Vliianie segregatsii i akkumuliatsii khlorokhina i daunorubitsina kletkami L (sublinii LSM) na aktivnost' lizosomnykh gidrolaz.