glutaminase and Pheochromocytoma

Glutamine metabolism is considered an important metabolic phenotype of proliferating tumor cells.. The objective of this study was to investigate the expression of glutamine metabolism-related and amino acid transporter proteins in adrenal cortical neoplasms (ACNs) and pheochromocytomas (PCCs) in the adrenal gland.. A tissue microarray was constructed for 132 cases of ACN (115 cases of adrenal cortical adenoma and 17 cases of adrenal cortical carcinoma) and 189 cases of PCC. Immunohistochemical staining for glutamine metabolism-related proteins GLS1 and GDH and amino acid transporter proteins SLC1A5, SLC7A5, and SLC7A11 as well as SDHB was performed and compared with clinicopathologic parameters.. The expression levels of GLS (. The expression of glutamine metabolism-related and amino acid transporter proteins in ACN and PCC is distinct and associated with prognosis.

Topics: Adrenal Gland Neoplasms; Adrenal Glands; Adult; Aged; Amino Acid Transport Systems, Basic; Biomarkers, Tumor; Female; Glutamate Dehydrogenase; Glutaminase; Humans; Male; Middle Aged; Pheochromocytoma

We investigated the effect of hypoxia on glutamate metabolism and uptake in rat pheochromocytoma (PC12) cells. Various key enzymes relevant to glutamate production, metabolism and transport were coordinately regulated by hypoxia. PC12 cells express two glutamate-metabolizing enzymes, glutamine synthetase (GS) and glutamate decarboxylase (GAD), as well as the glutamate-producing enzyme, phosphate-activated glutaminase (PAG). Exposure to hypoxia (1% O(2)) for 6 h or longer increased expression of GS mRNA and protein and enhanced GS enzymatic activity. In contrast, hypoxia caused a significant decrease in expression of PAG mRNA and protein, and also decreased PAG activity. In addition, hypoxia led to an increase in GAD65 and GAD67 protein levels and GAD enzymatic activity. PC12 cells express three Na(+)-dependent glutamate transporters; EAAC1, GLT-1 and GLAST. Hypoxia increased EAAC1 and GLT-1 protein levels, but had no effect on GLAST. Chronic hypoxia significantly enhanced the Na(+)-dependent component of glutamate transport. Furthermore, chronic hypoxia decreased cellular content of glutamate, but increased that of glutamine. Taken together, the hypoxia-induced changes in enzymes related to glutamate metabolism and transport are consistent with a decrease in the extracellular concentration of glutamate. This may have a role in protecting PC12 cells from the cytotoxic effects of glutamate during chronic hypoxia.

Topics: Adrenal Gland Neoplasms; Amino Acid Transport System X-AG; Animals; ATP-Binding Cassette Transporters; Biological Transport; Carrier Proteins; Cell Hypoxia; Cell Membrane; Excitatory Amino Acid Transporter 1; Excitatory Amino Acid Transporter 3; Gene Expression Regulation, Enzymologic; Gene Expression Regulation, Neoplastic; Glutamate Decarboxylase; Glutamate Plasma Membrane Transport Proteins; Glutamate-Ammonia Ligase; Glutamic Acid; Glutaminase; Isoenzymes; PC12 Cells; Pheochromocytoma; Rats; Reverse Transcriptase Polymerase Chain Reaction; Symporters