Corpus ID: 35393886

Secretion of gamma-glutamyl hydrolase in vitro.

  title={Secretion of gamma-glutamyl hydrolase in vitro.},
  author={B. O'Connor and R. Rotundo and Z. Nimec and J. McGuire and J. Galivan},
  journal={Cancer research},
  volume={51 15},
gamma-Glutamyl hydrolase (also known as conjugase) is a ubiquitous enzyme that has the capacity to cleave folyl- and antifolylpolyglutamates. This study has revealed that the enzyme is secreted by primary cultures of rat hepatocytes and by H35 hepatoma cells. H35 cells have lower cellular levels of gamma-glutamyl hydrolase than do hepatocytes but secrete a greater proportion of gamma-glutamyl hydrolase. More than 99% of the total enzyme from H35 cells accumulated in the medium after 48 h. The… Expand
gamma-Glutamyl hydrolase from human sarcoma HT-1080 cells: characterization and inhibition by glutamine antagonists.
Using the human HT-1080 sarcoma line, the secretion of GGH activity into media during culture and an acidic pH optimum for in vitro catalytic activity of the enzyme are observed, consistent with a lysosomal location for the enzyme. Expand
Multiple mechanisms of resistance to polyglutamatable and lipophilic antifolates in mammalian cells: role of increased folylpolyglutamylation, expanded folate pools, and intralysosomal drug sequestration.
These multiple resistance factors collectively result in a prominent increase in folate accumulation, an expansion of the intracellular folylpolyglutamate pool, and abolishment of the cytotoxic activity of polyglutamatable and lipophilic antifolates. Expand
The Reduced Folate Carrier (RFC) Is Cytotoxic to Cells under Conditions of Severe Folate Deprivation
Down-regulation of RFC and GGH may serve as a novel adaptive response to severe folate deficiency as upon severe short term folate deprivation RFC transport activity becomes detrimental as RFC, but not ATP-driven folate exporters, efficiently extrudes folate monoglutamates out of cells. Expand
Enzymes involved in folate metabolism and its implication for cancer treatment
  • Sung-Eun Kim
  • Chemistry, Medicine
  • Nutrition research and practice
  • 2020
This review discusses the effects of FPGS and GGH on chemosensitivity to cancer chemotherapeutic agents such as antifolates, such as methotrexate, and 5-fluorouracil and concludes that polyglutamylated (anti)folates are better substrates for intracellular folate-dependent enzymes and retained for longer within cells. Expand
High levels of γ-glutamyl hydrolase (GGH) are associated with poor prognosis and unfavorable clinical outcomes in invasive breast cancer
It is suggested that GGH serve as a potential biomarker of unfavorable clinical outcomes over short-term follow-up in breast cancer, and cytoplasmic GGH might play a relevant role in the development and progression of invasive breast cancer. Expand
Decreased folylpolyglutamate synthetase activity in tumors resistant to fluorouracil-folinic acid treatment: clinical data.
The link between clinical response to FU therapy for liver metastases of colorectal carcinoma and tumoral TS and FPGS activities is analyzed to establish for the first time the potential importance of tumoral FPGs activity for assessing FU-folinic acid responsiveness in the clinical setting. Expand
Disparate mechanisms of antifolate resistance provoked by methotrexate and its metabolite 7-hydroxymethotrexate in leukemia cells: implications for efficacy of methotrexate therapy.
This is the first demonstration that 7-OHMTX can provoke distinct modalities of antifolate resistance compared with the parent drug MTX, and the implications for MTX efficacy and strategies to circumvent MTX resistance are discussed. Expand
Classification Of Ex Vivo Methotrexate Resistance In Acute Lymphoblastic and Myeloid Leukaemia
Improved survival rate suggests that cellular drug resistance can be partially overcome by dose intensification, and clinically relevant mechanisms of MTX resistance, as observed in samples of acute leukaemia patients are described. Expand
Attributable to Enhanced Energy-dependent Drug Efflux Multidrug-resistant MCF 7 Breast Cancer Cell Line Is Methotrexate Cross-Resistance in a Mitoxantrone-selected Updated
Cellular resistance to the antifolate methotrexate (MTX) is often caused by target amplification, uptake defects, or alterations in polyglutamylation. Here we have examined MTX cross-resistance in aExpand
Methotrexate cross-resistance in a mitoxantrone-selected multidrug-resistant MCF7 breast cancer cell line is attributable to enhanced energy-dependent drug efflux.
The data suggest that a novel MTX-specific efflux pump may be involved in this unusual cross-resistance phenotype, and members of the MRP protein family of transport proteins, which had previously been implicated in MTX resistance, were not found to be overexpressed in the MCF7/MX cells. Expand