Acetylleucine chloromethyl ketone, an inhibitor of acylpeptide hydrolase, induces apoptosis of U937 cells.
Acetylleucine chloromethyl ketone (ALCK), an inhibitor of acylpeptide hydrolase (ACPH), inhibited the growth of human monoblastic U937 cells in a dose- and time-dependent manner. Morphology of the ALCK-exposed cells showed typical apoptosis, judging from the nuclear condensation and segmentation. Chromosomal DNA of U937 cells treated with ALCK showed an internucleosomal ladder-like pattern on electrophoresis, being characteristic of apoptosis. Of the other leucine chloromethyl ketone analogues, butyloylleucine chloromethyl ketone (BLCK) induced a weak ladder-like formation but caploylleucine chloromethyl ketone (CLCK)barely did. On the other hand, intracellular ACPH activity of U937 cells was strongly inhibited by culturing with ALCK, moderately with BLCK, and not with CLCK. These findings indicate that the inhibition of ACPH activity leads to apoptosis and suggest that ACPH may play a vital role in eukaryotic cells.
Yamaguchi
M
M
Showa College of Pharmaceutical Sciences, Higashi-tamagawagakuen, Machida, Tokyo, 194-8543, Japan.
Kambayashi
D
D
Toda
J
J
Sano
T
T
Toyoshima
S
S
Hojo
H
H
D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D002455:Cell Division / Q000187:drug effects; D053938:DNA Fragmentation / Q000187:drug effects; D006801:Humans; D010447:Peptide Hydrolases / Q000378:metabolism*; D011480:Protease Inhibitors / Q000494:pharmacology*; D020298:U937 Cells
D000590:Amino Acid Chloromethyl Ketones; D011480:Protease Inhibitors; C121811:acetylleucine chloromethyl ketone; D010447:Peptide Hydrolases; C038220:acylaminoacyl-peptidase