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Hydrogen peroxide produced during γ‐glutamyl transpeptidase activity is involved in prevention of apoptosis and maintainance of proliferation in U937 cells
Author(s) -
DEL BELLO BARBARA,
PAOLICCHI ALDO,
COMPORTI MARIO,
POMPELLA ALFONSO,
MAELLARO EMILIA
Publication year - 1999
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.13.1.69
Subject(s) - apoptosis , catalase , reactive oxygen species , chemistry , programmed cell death , dna fragmentation , hydrogen peroxide , cell growth , trolox , apoptotic dna fragmentation , biochemistry , superoxide , u937 cell , oxidative stress , dna damage , microbiology and biotechnology , biology , enzyme , dna , antioxidant capacity
It has been reported in several cell lines that exposure to low levels of reactive oxygen species can exert a stimulatory effect on their proliferation. We have previously shown that mild oxidative conditions can also counteract apoptotic stimuli. A constitutive cellular production of low levels of superoxide and hydrogen peroxide originates from various sources; among these, γ‐glutamyl transpeptidase (GGT), the plasma membrane‐bound activity in charge of metabolizing extracellular reduced glutathione, has recently been included. Since the inhibition of GGT is a sufficient stimulus for the induction of apoptosis in selected cell lines, we investigated whether this effect might result from the suppression of the mentioned GGT‐dependent prooxidant reactions, on the theory that the latter may represent a basal antiapoptotic and proliferative signal for the cell. Experiments showed that: 1 ) GGT activity in U937 monoblastoid cells is associated with the production of low levels of hydrogen peroxide, and two independent GGT inhibitors cause a dose‐dependent decrease of such GGT‐dependent production of H 2 O 2 ; 2 ) GGT inhibition with acivicin results in cell growth arrest, and induces cell death and DNA fragmentation with the ladder appearance of apoptosis; 3) treatment of cells with catalase—and even more with Trolox C—is able to decrease their proliferative rate; 4 ) GGT inhibition (with suppression of H 2 O 2 production) results in a down‐regulation of poly(ADP‐ribose) polimerase (PARP) activity, which precedes the proteolytic cleavage of PARP molecule, such as that typically induced by caspases. The reported data suggest that the low H 2 O 2 levels originating as a by‐product during GGT activity are able to act as sort of a ‘life signal’ in U937 cells, insofar as they can maintain cell proliferation and protect against apoptosis, possibly through an up‐regulation of PARP activity. —Del Bello, B., Paolicchi, A., Comporti, M., Pompella, A., Maellaro, E. Hydrogen peroxide produced during γ‐glutamyl transpeptidase activity is involved in prevention of apoptosis andmaintainance of proliferation in U937 cells. FASEB J. 13, 69–79 (1999)