Dipeptidyl peptidase II and leukocyte cell death.
Dipeptidyl peptidase (DPP) II (E.C. 3.4.14.2) is an intracellular protease that releases, preferably at acidic pH, N-terminal dipeptides from oligopeptides with Pro or Ala in the penultimate position. The natural substrates and the physiological role of DPPII remain unclear. The aim of the present study was to investigate the involvement of DPPII activity in different forms of cell death (apoptosis, necrosis and autophagy) in human leukocytes. We determined specific DPP activities in leukocytes. Compared to other subpopulations of peripheral blood mononuclear cells (PBMC), we observed relatively high DPPII specific activity in monocytic cells, opening new perspectives for further investigation of the DPPII functions. A second intriguing finding was that DPPII specific activity increased during necrosis, whereas induction of apoptosis or autophagy did not affect any of the dipeptidyl peptidase activities. Finally, we showed that inhibition of DPPII (>90%) using the in vitro applicable, highly potent (K(i) of 0.082+/-0.048 nM) and selective DPPII inhibitor UAMC00039, did not induce any form of cell death in leukocytes. These data are of importance for a more precise interpretation of the in vitro and in vivo effects of other dipeptidyl peptidase inhibitors.
Maes
Marie-Berthe
MB
Laboratory of Medical Biochemistry, University of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Belgium.
Martinet
Wim
W
Schrijvers
Dorien M
DM
Van der Veken
Pieter
P
De Meyer
Guido R Y
GR
Augustyns
Koen
K
Lambeir
Anne-Marie
AM
Scharpé
Simon
S
De Meester
Ingrid
I
D017209:Apoptosis / Q000502:physiology*; D001343:Autophagy / Q000502:physiology*; D002460:Cell Line; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / Q000037:antagonists & inhibitors / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000201:enzymology*; D009336:Necrosis / Q000378:metabolism*; D020298:U937 Cells
D004791:Enzyme Inhibitors; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; C100151:dipeptidyl peptidase II