Reanalysis of the involvement of γ‐glutamyl transpeptidase in the cell activation process

Abstract

The inhibitor of Q Q-glutamyl transpeptidase (Q Q-GT) acivicin modulates cellular responses including growth, myeloid maturation and apoptosis. Whether these effects result from the inhibition of Q Q-GT enzyme activity remains unclear. We compared the cellular effects of acivicin against a more potent and specific inhibitor of Q Q-GT (L-2-amino-4-boronobutanoic acid (L-ABBA)) in Q Q-GT-negative (B lymphoblastoid Ramos) and Q Q-GT-positive (myelomonocytic HL-60, Q Q-GT-transfected Ramos) cell lines. Under non-oxidative stress conditions, acivicin-induced cell growth arrest, apoptosis and macrophage maturation occurred independent of Q Q-GT while L-ABBA did not influence any of these processes. Acivicin triggered tyrosine phosphorylation and increased nuclear factor U UB activity. Further insight into the role of Q Q-GT in cellular processes is needed. ß

Boron Containing Compounds as Protease Inhibitors

“…A study following this finding, where the cellular effects of acivicin, an inhibitor of γ-glutamyl transpeptidase (γ-GT) that modulates cellular responses including growth, myeloid maturation, and apoptosis, against the more potent and specific inhibitor of γ-GT ( l -2-amino-4-boronobutanoic acid, l -ABBA) in γ-GT-negative (B lymphoblastoid Ramos) and γ-GT-positive (myelomonocytic HL-60, γ-GT-transferred Ramos) cell lines were compared . Under nonoxidative stress conditions, acivicin-induced cell growth arrest, apoptosis, and macrophage maturation occurred independent of γ-GT, while l -ABBA did not influence any of these processes.…”

γ-Glutamyl transpeptidase expression in Ewing's sarcoma cells:up-regulation by interferons

“…Previous studies have implicated γ-GT in the regulation of cell growth and survival. Our recent observations however suggest a lack of participation of γ-GT in these cellular processes [50]. Interestingly, a molecular association between cell surface γ-GT and some members of the tetraspan 4 family, including CD53, CD81 and CD82 has been reported [24].…”

Employing Pancreatic Tumor γ-Glutamyltransferase for Therapeutic Delivery

“…On some occasions the γGT competitive inhibitor, l -2-amino-4-boronobutanoic acid (ABBA), was added. A concentration of 10 μM ABBA was employed, which is >100-fold the concentration of ABBA that results in half-maximal inhibition of purified or cell surface γGT activity . ABBA was provided by Dr. R. E. London (NIEHS, National Institutes of Health, Research Triangle Park, NC).…”

“…A concentration of 10 μM ABBA was employed, which is >100-fold the concentration of ABBA that results in half-maximal inhibition of purified or cell surface γGT activity. 14 ABBA was provided by Dr. R. E. London (NIEHS, National Institutes of Health, Research Triangle Park, NC). The culture supernatant was clarified using an Amicon Ultra-0.5 3K centrifugal filter (Millipore, Billerica, MA), and samples were resolved by HPLC (Thermo Fisher Scientific, Scoresby, VIC, Australia) on a Zorbax Eclipse XDB-C18 column (4.6 × 150 mm, 5 μm; Agilent Technologies, Mulgrave, VIC, Australia) using a mobile phase of acetonitrile−water (25:75 v/v), a flow rate of 0.5 mL/min, and detection by absorbance at 256 nm.…”