Acivicin Induces Apoptosis Independently of γ-Glutamyltranspeptidase Activity

Aberkane, Hayet; Frank, Patricia; Galteau, Marie‐Madeleine; Wellman, Maria

doi:10.1006/bbrc.2001.5297

Cited by 9 publications

(10 citation statements)

References 28 publications

(18 reference statements)

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“…Therefore only a qualitative assessment of viability can be made. Acivicin has been shown to induce apoptosis in γ-GT deficient cells (Aberkane et al, 2001), but in the present study the viability of acivicin treated acini appeared no different from untreated acini. Lactose secretion over the 0to 4-h period of incubation in the presence of acivicin decreased by 32% (P < 0.05).…”

Section: Incubation Timecontrasting

confidence: 76%

γ-Glutamyl Transpeptidase Inhibition Suppresses Milk Protein Synthesis in Isolated Ovine Mammary Cells

Johnston

Kitson

Tweedie

et al. 2004

Journal of Dairy Science

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The membrane spanning enzyme gamma-glutamyl transpeptidase (gamma-GT; EC 2.3.2.2) catalyses the breakdown of the tripeptide glutathione and uses free amino acids (AA) to form gamma-glutamyl transpeptidase (GT) AA that become transported into cells and converted back into free AA. gamma-Glutamyl transpeptidase activity has been shown to be important for mammary AA uptake in rodent systems, and while gamma-GT activity is high in lactating bovine mammary tissue, the role of this enzyme in milk protein synthesis of the ruminant has not been defined. The present study shows that gamma-GT activity in the ovine mammary gland, like that of rodents, increases during pregnancy and peaks early in lactation. Acivicin, a well-known inhibitor of gamma-GT, decreased gamma-GT activity in acini isolated from the ovine mammary gland and did not have secondary toxicity effects on cell viability or the uptake of radiolabeled amino-isobutyric acid. Isolated ovine acini were incubated in the presence of radiolabeled leucine, and incorporation of label into secreted protein increased during incubation. Incubation of acini with acivicin decreased milk protein secretion by 75%, indicating that gamma-GT plays an important role in milk protein production in the ruminant. Acivicin did not inhibit secretion of specific caseins but caused a global decrease in individual proteins suggesting that gamma-GT may be responsible for providing a complement of AA for milk protein synthesis.

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Section: Incubation Timecontrasting

confidence: 76%

γ-Glutamyl Transpeptidase Inhibition Suppresses Milk Protein Synthesis in Isolated Ovine Mammary Cells

Johnston

Kitson

Tweedie

et al. 2004

Journal of Dairy Science

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“…Other glutamine dependent amido-transferases, mainly those involved in nucleotide biosynthesis, are also inhibited, which leads to changes in cell proliferation and apoptosis. [284,285] The use of donor-site directed compounds in vivo is therefore limited. As alternative gGT inhibitors, monoclonal antibodies were recently developed that specifically inhibited the formation of the tetrahedral complex between the enzyme and its substrate.…”

Section: G-glutamyl Transpeptidasementioning

confidence: 99%

Glutathione Conjugates and Their Synthetic Derivatives as Inhibitors of Glutathione-Dependent Enzymes Involved in Cancer and Drug Resistance

Burg

Mulder

2002

Drug Metabolism Reviews

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Alterations in levels of glutathione (GSH) and glutathione-dependent enzymes have been implicated in cancer and multidrug resistance of tumor cells. The activity of a number of these, the multidrug resistance-associated protein 1, glutathione S-transferase, DNA-dependent protein kinase, glyoxalase I, and gamma-glutamyl transpeptidase, can be inhibited by GSH-conjugates and synthetic analogs thereof. In this review we focus on the function of these enzymes and carriers in cancer and anti-cancer drug resistance, in relation to their inhibition by GSH-conjugate analogs.

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“…Comparative experiments with L ‐ABBA showed that, in addition to cell proliferation, acivicin also affected myeloid differentiation and apoptosis independently of its inhibition of γ‐GT. The γ‐GT‐independent effect of acivicin on apoptosis has recently been observed in V79 Chinese hamster cells transfected with human γ‐GT [15]. The molecular mechanisms behind all forms of acivicin‐induced growth arrest/apoptosis are not known.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2001

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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

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Acivicin Induces Apoptosis Independently of γ-Glutamyltranspeptidase Activity

Cited by 9 publications

References 28 publications

γ-Glutamyl Transpeptidase Inhibition Suppresses Milk Protein Synthesis in Isolated Ovine Mammary Cells

γ-Glutamyl Transpeptidase Inhibition Suppresses Milk Protein Synthesis in Isolated Ovine Mammary Cells

Glutathione Conjugates and Their Synthetic Derivatives as Inhibitors of Glutathione-Dependent Enzymes Involved in Cancer and Drug Resistance

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

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