Properties of the Pig Renal Mitochondrial Glutamine Transporter

2015 ◽  
pp. 7-12
Author(s):  
B. Roberg ◽  
I. Aa. Torgner ◽  
E. Kvamme
Keyword(s):  
Glutamine Transporter

Cellular and molecular basis of increased ammoniagenesis in potassium deprivation

2011 ◽  
Vol 301 (5) ◽  
pp. F969-F978 ◽  
Author(s):  
Shaikh Abu Hossain ◽  
Farrukh A. Chaudhry ◽  
Kamyar Zahedi ◽  
Faraaz Siddiqui ◽  
Hassane Amlal
Keyword(s):  
Phosphoenolpyruvate Carboxykinase ◽  
Molecular Mechanisms ◽  
Intracellular Acidosis ◽  
Deficient Diet ◽  
Proximal Tubule Cells ◽  
Glutamine Transporter ◽  
Additive Increase ◽  
Acid Base Status ◽  
Low K ◽  
Stimulation Of

Hypokalemia is associated with increased ammoniagenesis and stimulation of net acid excretion by the kidney in both humans and experimental animals. The molecular mechanisms underlying these effects remain unknown. Toward this end, rats were placed in metabolic cages and fed a control or K+-deficient diet (KD) for up to 6 days. Rats subjected to KD showed normal acid-base status and serum electrolytes composition. Interestingly, urinary NH4+ excretion increased significantly and correlated with a parallel decrease in urine K+ excretion in KD vs. control animals. Molecular studies showed a specific upregulation of the glutamine transporter SN1, which correlated with the upregulation of glutaminase (GA), glutamate dehydrogenase (GDH), and phosphoenolpyruvate carboxykinase. These effects occurred as early as day 2 of KD. Rats subjected to a combined KD and 280 mM NH4Cl loading (to induce metabolic acidosis) for 2 days showed an additive increase in NH4+ excretion along with an additive increment in the expression levels of ammoniagenic enzymes GA and GDH compared with KD or NH4Cl loading alone. The incubation of cultured proximal tubule cells NRK 52E or LLC-PK1 in low-K+ medium did not affect NH4+ production and did not alter the expression of SN1, GA, or GDH in NRK cells. These results demonstrate that K+ deprivation stimulates ammoniagenesis through a coordinated upregulation of glutamine transporter SN1 and ammoniagenesis enzymes. This effect is developed before the onset of hypokalemia. The signaling pathway mediating these events is likely independent of KD-induced intracellular acidosis. Finally, the correlation between increased NH4+ production and decreased K+ excretion indicate that NH4+ synthesis and transport likely play an important role in renal K+ conservation during hypokalemia.

Glutamine transporter in crypts compensates for loss of villus absorption in bovine cryptosporidiosis

2001 ◽  
Vol 281 (3) ◽  
pp. G645-G653 ◽  
Author(s):  
Anthony Blikslager ◽  
Elaine Hunt ◽  
Richard Guerrant ◽  
Marc Rhoads ◽  
Robert Argenzio
Keyword(s):  
Amino Acid ◽  
Villous Atrophy ◽  
Acid Transport ◽  
Synthesis Inhibitor ◽  
Amino Acid Transport System ◽  
Ussing Chambers ◽  
Nacl Absorption ◽  
Combined Use ◽  
Glutamine Transporter ◽  
Mucosal Surface Area

Cryptosporidium parvum infection represents a significant cause of diarrhea in humans and animals. We studied the effect of luminally applied glutamine and the PG synthesis inhibitor indomethacin on NaCl absorption from infected calf ileum in Ussing chambers. Infected ileum displayed a decrease in both mucosal surface area and NaCl absorption. Indomethacin and glutamine or its stable derivative alanyl-glutamine increased the net absorption of Na+in infected tissue in an additive manner and to a greater degree than in controls. Immunohistochemical and Western blot studies showed that in control animals neutral amino acid transport system ASC was present in villus and crypts, whereas in infected animals, ASC was strongly present only on the apical border of crypts. These results are consistent with PGs mediating the altered NaCl and water absorption in this infection. Our findings further illustrate that the combined use of a PG synthesis inhibitor and glutamine can fully stimulate Na+and Cl−absorption despite the severe villous atrophy, an effect associated with increased expression of a Na+-dependent amino acid transporter in infected crypts.

Hepatic glutamine transporter activation in burn injury: role of amino acids and phosphatidylinositol-3-kinase

2000 ◽  
Vol 278 (4) ◽  
pp. G532-G541 ◽  
Author(s):  
Timothy M. Pawlik ◽  
Rüdiger Lohmann ◽  
Wiley W. Souba ◽  
Barrie P. Bode
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Burn Injury ◽  
Cell Swelling ◽  
Phosphatidylinositol 3 Kinase ◽  
Pi3k Inhibitors ◽  
Glutamine Transporter ◽  
Hypermetabolic State ◽  
Phosphatidylinositol 3

Burn injury elicits a marked, sustained hypermetabolic state in patients characterized by accelerated hepatic amino acid metabolism and negative nitrogen balance. The transport of glutamine, a key substrate in gluconeogenesis and ureagenesis, was examined in hepatocytes isolated from the livers of rats after a 20% total burn surface area full-thickness scald injury. A latent and profound two- to threefold increase in glutamine transporter system N activity was first observed after 48 h in hepatocytes from injured rats compared with controls, persisted for 9 days, and waned toward control values after 18 days, corresponding with convalescence. Further studies showed that the profound increase was fully attributable to rapid posttranslational transporter activation by amino acid-induced cell swelling and that this form of regulation may be elicited in part by glucagon. The phosphatidylinositol-3-kinase (PI3K) inhibitors wortmannin and LY-294002 each significantly attenuated transporter stimulation by amino acids. The data suggest that PI3K-dependent system N activation by amino acids may play an important role in fueling accelerated hepatic nitrogen metabolism after burn injury.

scholarly journals Enhancement of Glutamine Utilization in Bacillus subtilis through the GlnK-GlnL Two-Component Regulatory System

2005 ◽  
Vol 187 (14) ◽  
pp. 4813-4821 ◽  
Author(s):  
Takenori Satomura ◽  
Daisuke Shimura ◽  
Kei Asai ◽  
Yoshito Sadaie ◽  
Kazutake Hirooka ◽  
...  
Keyword(s):  
Transcription Initiation ◽  
Culture Medium ◽  
Regulatory System ◽  
Direct Repeat ◽  
Northern Analysis ◽  
Two Component System ◽  
Dnase I Footprinting ◽  
Glutamine Transporter ◽  
Two Component ◽  
Extension Analysis

ABSTRACT During DNA microarray analysis, we discovered that the GlnK-GlnL (formerly YcbA-YcbB) two-component system positively regulates the expression of the glsA-glnT (formerly ybgJ-ybgH) operon in response to glutamine in the culture medium on Northern analysis. As a result of gel retardation and DNase I footprinting analyses, we found that the GlnL protein interacts with a region (bases −13 to −56; +1 is the transcription initiation base determined on primer extension analysis of glsA-glnT) in which a direct repeat, TTTTGTN4TTTTGT, is present. Furthermore, the glsA and glnT genes were biochemically verified to encode glutaminase and glutamine transporter, respectively.

scholarly journals Targeting of glutamine transporter ASCT2 and glutamine synthetase suppresses gastric cancer cell growth

2018 ◽  
Vol 144 (5) ◽  
pp. 821-833 ◽  
Author(s):  
Jianxin Ye ◽  
Qiang Huang ◽  
Jie Xu ◽  
Jinsheng Huang ◽  
Jinzhou Wang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Growth ◽  
Glutamine Synthetase ◽  
Cancer Cell ◽  
Gastric Cancer Cell ◽  
Cancer Cell Growth ◽  
Glutamine Transporter

Rat liver endothelial cell glutamine transporter and glutaminase expression contrast with parenchymal cells

1999 ◽  
Vol 276 (3) ◽  
pp. G743-G750 ◽  
Author(s):  
Rüdiger Lohmann ◽  
Wiley W. Souba ◽  
Barrie P. Bode
Keyword(s):  
Endothelial Cells ◽  
Amino Acid ◽  
Cell Types ◽  
Male Rats ◽  
Specific Cell ◽  
Liver Endothelial Cell ◽  
Glutamine Transporter ◽  
Health And Disease ◽  
Parenchymal Cells ◽  
Functional Analyses

Despite the central role of the liver in glutamine homeostasis in health and disease, little is known about the mechanism by which this amino acid is transported into sinusoidal endothelial cells, the second most abundant hepatic cell type. To address this issue, the transport ofl-glutamine was functionally characterized in hepatic endothelial cells isolated from male rats. On the basis of functional analyses, including kinetics, cation substitution, and amino acid inhibition, it was determined that a Na+-dependent carrier distinct from system N in parenchymal cells, with properties of system ASC or B0, mediated the majority of glutamine transport in hepatic endothelial cells. These results were supported by Northern blot analyses that showed expression of the ATB0 transporter gene in endothelial but not parenchymal cells. Concurrently, it was determined that, whereas both cell types express glutamine synthetase, hepatic endothelial cells express the kidney-type glutaminase isozyme in contrast to the liver-type isozyme in parenchymal cells. This represents the first report of ATB0 and kidney-type glutaminase isozyme expression in the liver, observations that have implications for roles of specific cell types in hepatic glutamine homeostasis in health and disease.

scholarly journals Myeloma Cells Deplete Bone Marrow Glutamine and Inhibit Osteoblast Differentiation Limiting Asparagine Availability

Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3267
Author(s):  
Martina Chiu ◽  
Denise Toscani ◽  
Valentina Marchica ◽  
Giuseppe Taurino ◽  
Federica Costa ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Amino Acid ◽  
Stromal Cells ◽  
Osteoblast Differentiation ◽  
Essential Amino Acids ◽  
Asparagine Synthetase ◽  
Osteolytic Lesions ◽  
Glutamine Transporter

Multiple myeloma (MM) cells consume huge amounts of glutamine and, as a consequence, the amino acid concentration is lower-than-normal in the bone marrow (BM) of MM patients. Here we show that MM-dependent glutamine depletion induces glutamine synthetase in stromal cells, as demonstrated in BM biopsies of MM patients, and reproduced in vitro by co-culturing human mesenchymal stromal cells (MSCs) with MM cells. Moreover, glutamine depletion hinders osteoblast differentiation of MSCs, which is also severely blunted by the spent, low-glutamine medium of MM cells, and rescued by glutamine restitution. Glutaminase and the concentrative glutamine transporter SNAT2 are induced during osteoblastogenesis in vivo and in vitro, and both needed for MSCs differentiation, pointing to enhanced the requirement for the amino acid. Osteoblastogenesis also triggers the induction of glutamine-dependent asparagine synthetase (ASNS), and, among non-essential amino acids, asparagine rescues differentiation of glutamine-starved MSCs, by restoring the transcriptional profiles of differentiating MSCs altered by glutamine starvation. Thus, reduced asparagine availability provides a mechanistic link between MM-dependent Gln depletion in BM and impairment of osteoblast differentiation. Inhibition of Gln metabolism in MM cells and supplementation of asparagine to stromal cells may, therefore, constitute novel approaches to prevent osteolytic lesions in MM.

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