Reanalysis of the involvement of gamma-glutamyl transpeptidase in the cell activation process.
The inhibitor of gamma-glutamyl transpeptidase (gamma-GT) acivicin modulates cellular responses including growth, myeloid maturation and apoptosis. Whether these effects result from the inhibition of gamma-GT enzyme activity remains unclear. We compared the cellular effects of acivicin against a more potent and specific inhibitor of gamma-GT (L-2-amino-4-boronobutanoic acid (L-ABBA)) in gamma-GT-negative (B lymphoblastoid Ramos) and gamma-GT-positive (myelomonocytic HL-60, gamma-GT-transfected Ramos) cell lines. Under non-oxidative stress conditions, acivicin-induced cell growth arrest, apoptosis and macrophage maturation occurred independent of gamma-GT while L-ABBA did not influence any of these processes. Acivicin triggered tyrosine phosphorylation and increased nuclear factor kappaB activity. Further insight into the role of gamma-GT in cellular processes is needed.
Antczak
C
C
Institut Curie, Section de Recherche, INSERM U365, Paris, France.
Karp
D R
DR
London
R E
RE
Bauvois
B
B
D017209:Apoptosis / Q000187:drug effects*; D001896:Boron Compounds / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D019833:Genistein / Q000494:pharmacology; D018922:HL-60 Cells; D006801:Humans; D007555:Isoxazoles / Q000494:pharmacology*; D008264:Macrophages / Q000166:cytology / Q000187:drug effects*; D016328:NF-kappa B / Q000378:metabolism; D013050:Spectrometry, Fluorescence; D014162:Transfection; D020032:Tyrphostins / Q000494:pharmacology; D005723:gamma-Glutamyltransferase / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*
C426904:2-amino-4-boronobutanoic acid; D001896:Boron Compounds; D007555:Isoxazoles; D016328:NF-kappa B; D020032:Tyrphostins; D019833:Genistein; D005723:gamma-Glutamyltransferase; C006303:acivicin