Induction of apoptosis in primary culture of rat hepatocytes by protease inhibitors.
There is growing evidence that suggests the involvement of intracellular proteases in the process of apoptosis or programmed cell death. In this study, we have demonstrated that leupeptin, a cysteine protease inhibitor, can significantly increase the incidence of both apoptotic nuclear morphology change and internucleosomal DNA fragmentation in primary cultured hepatocytes in the absence of known apoptotic stimuli for hepatocytes. On the other hand, aspartic and serine protease inhibitors showed little or no effects on the apoptotic changes. In addition, we found that the apoptotic changes could be induced by chloroquine, an inhibitor of lysosomal proteolysis, but could not be induced by calpain inhibitors. These data suggest that inhibition of lysosomal cysteine proteases may induce apoptosis in primary cultured hepatocytes.
Maeda
S
S
Department of Chemistry, National Industrial Research Institute of Nagoya, Japan.
Lin
K H
KH
Inagaki
H
H
Saito
T
T
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone / Q000494:pharmacology; D002403:Cathepsins / Q000494:pharmacology; D002467:Cell Nucleus / Q000187:drug effects; D002478:Cells, Cultured; D002738:Chloroquine / Q000494:pharmacology; D003546:Cysteine Endopeptidases / Q000494:pharmacology; D004587:Electrophoresis, Agar Gel; D005260:Female; D006023:Glycoproteins / Q000494:pharmacology; D007976:Leupeptins / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008247:Lysosomes / Q000378:metabolism; D008856:Microscopy, Fluorescence; D011480:Protease Inhibitors / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D016212:Transforming Growth Factor beta / Q000494:pharmacology
D006023:Glycoproteins; D007976:Leupeptins; D011480:Protease Inhibitors; D016212:Transforming Growth Factor beta; C039304:calpain inhibitors; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone; D002738:Chloroquine; D002403:Cathepsins; D003546:Cysteine Endopeptidases; C032854:leupeptin