Increased ecto-metallopeptidase activity in cells undergoing apoptosis.
Release from the cell surface of a variety of growth factors, cytokines, and proteases follows exposure to genetically stressful agents capable of inducing apoptosis and necrosis. Increased ectoprotease activity is responsible for their release. We show that increased activity of several metalloproteases on the HeLa cell surface occurs after stresses due to UVC, actinomycin D, cycloheximide, and cisplatinum, which induce the release of transforming growth factor-alpha (TGFalpha) and other bioactive molecules. The ectoprotease activities increase preferentially on apoptotic cells, while little change occurs in viable cells. Gross decreases, except for the putative TGFalphaase activity, accompany necrosis. These changes may contribute to tissue repair and the absence of an inflammatory reaction to apoptotic cell death. They appear to be due to preferential enzyme activation or to retention by cells undergoing significant categorical decreases in protein content.
Piva
T J
TJ
QCF Cancer Research Unit, Queensland Institute of Medical Research and Joint Experimental Oncology Program, University of Queensland, Brisbane, Queensland 4702, Australia. t.piva@cqu.edu.au
Davern
C M
CM
Francis
K G
KG
Chojnowski
G M
GM
Hall
P M
PM
Ellem
K A
KA
D000626:Aminopeptidases / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects*; D002462:Cell Membrane / Q000201:enzymology*; D002945:Cisplatin / Q000494:pharmacology; D003513:Cycloheximide / Q000494:pharmacology; D053938:DNA Fragmentation; D003609:Dactinomycin / Q000494:pharmacology; D005434:Flow Cytometry; D006367:HeLa Cells; D006801:Humans; D007930:Leucine / Q000031:analogs & derivatives / Q000494:pharmacology; D008666:Metalloendopeptidases / Q000378:metabolism*; D009153:Mutagens / Q000494:pharmacology; D010455:Peptides / Q000378:metabolism; D011480:Protease Inhibitors / Q000494:pharmacology; D016211:Transforming Growth Factor alpha / Q000378:metabolism; D014466:Ultraviolet Rays
D009153:Mutagens; D010455:Peptides; D011480:Protease Inhibitors; D016211:Transforming Growth Factor alpha; D003609:Dactinomycin; D003513:Cycloheximide; D000626:Aminopeptidases; D008666:Metalloendopeptidases; D007930:Leucine; C012211:ubenimex; D002945:Cisplatin