scholarly journals The role of the glutamine transporter ASCT2 in antineoplastic therapy

2021 ◽  
Author(s):  
Estefânia Teixeira ◽  
Cláudia Silva ◽  
Fátima Martel
Keyword(s):  
Antineoplastic Therapy ◽  
Glutamine Transporter

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 The Role of Nrf2 Transcription Factor and Sp1-Nrf2 Protein Complex in Glutamine Transporter SN1 Regulation in Mouse Cortical Astrocytes Exposed to Ammonia

2021 ◽  
Vol 22 (20) ◽  
pp. 11233
Author(s):  
Katarzyna Dąbrowska ◽  
Katarzyna Skowrońska ◽  
Mariusz Popek ◽  
Jan Albrecht ◽  
Magdalena Zielińska
Keyword(s):  
Protein Level ◽  
Nuclear Translocation ◽  
Mapk Pathway ◽  
Ammonia Toxicity ◽  
Dependent Manner ◽  
Glutamine Transporter ◽  
The Brain ◽  
Nrf2 Protein ◽  
Glutamine Uptake

Ammonia toxicity in the brain primarily affects astrocytes via a mechanism in which oxidative stress (OS), is coupled to the imbalance between glutamatergic and GABAergic transmission. Ammonia also downregulates the astrocytic N system transporter SN1 that controls glutamine supply from astrocytes to neurons for the replenishment of both neurotransmitters. Here, we tested the hypothesis that activation of Nrf2 is the process that links ammonia-induced OS formation in astrocytes to downregulation and inactivation of SN1 and that it may involve the formation of a complex between Nrf2 and Sp1. Treatment of cultured cortical mouse astrocytes with ammonia (5 mM NH4Cl for 24 h) evoked Nrf2 nuclear translocation, increased its activity in a p38 MAPK pathway-dependent manner, and enhanced Nrf2 binding to Slc38a3 promoter. Nrf2 silencing increased SN1 mRNA and protein level without influencing astrocytic [3H]glutamine transport. Ammonia decreased SN1 expression in Nrf2 siRNA treated astrocytes and reduced [3H]glutamine uptake. In addition, while Nrf2 formed a complex with Sp1 in ammonia-treated astrocytes less efficiently than in control cells, treatment of astrocytes with hybrid-mode inactivated Sp1-Nrf2 complex (Nrf2 silencing + pharmacological inhibition of Sp1) did not affect SN1 protein level in ammonia-treated astrocytes. In summary, the results document that SN1 transporter dysregulation by ammonia in astrocytes involves activation of Nrf2 but does not require the formation of the Sp1-Nrf2 complex.

scholarly journals Relationships Between Slc1a5 and Osteoclastogenesis

2021 ◽  
Author(s):  
Hideki Tsumura ◽  
Miyuki Shindo ◽  
Morihiro Ito ◽  
Arisa Igarashi ◽  
Kazue Takeda ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Cells ◽  
Osteoclast Formation ◽  
Tartrate Resistant Acid Phosphatase ◽  
Glutamine Transporter ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Glutamine Uptake ◽  
Marrow Cells

Slc1a5 (ASCT2) encodes a small neutral amino-acid exchanger and is the most well-studied glutamine transporter in cancercells. To investigate the role of Slc1a5 in osteoclastogenesis, we developed Slc1a5-deficient mice by using a conventional gene-targeting approach. The Slc1a5−/− mice showed no obvious abnormalities in growth. Glutamine uptake was assessed in Slc1a5+/+ and Slc1a5−/− bone marrow cells stimulated with RANKL. The rate of glutamine uptake in Slc1a5−/− bone marrow cellswas reduced to 70% of that of cells from Slc1a5+/+ bone marrow. To confirm the involvement of Slc1a5 in osteoclast formation, bone marrow cells derived from Slc1a5+/+ or Slc1a5−/− mice were stimulated with RANKL and macrophage colony-stimulating factor and stained with tartrate-resistant acid phosphatase. The bone resorption activity and actin ring formation of stimulated cells were measured. The formation of multinucleated osteoclasts in bone marrow cells isolated from Slc1a5−/− mice was severely impaired compared with those from Slc1a5+/+ mice. RANKL-induced expression of ERK, NFκB, p70S6K, and NFATc1 was suppressed in Slc1a5−/− osteoclasts. These results show that Slc1a5 plays an important role in osteoclast formation.

Hormonal and Na+ effect on renal glutamine uptake

1989 ◽  
Vol 256 (6) ◽  
pp. F1027-F1033
Author(s):  
T. C. Welbourne
Keyword(s):  
Acid Base Balance ◽  
Extracellular Compartment ◽  
Glutamine Transporter ◽  
Base Balance ◽  
Flow Through ◽  
Na Effect ◽  
Glutamine Uptake ◽  
Rat Kidneys

The flux of glutamine through cellular PDG or extracellular gamma-glutamyltransferase may reflect competition between the membrane glutamine transporter and extracellular hydrolysis. To test this model, kidneys from nonacidotic (NA) and chronically acidotic rats were isolated and perfused with glutamine in a Na+ media and then with a media in which choline replaced Na+. Replacing Na+ abolished the Na+ gradient and completely eliminated the transport of filtered glutamine back into the perfusate. Nevertheless NH4+ production and glutamine utilization remained intact while glutamate accumulated in the extracellular compartments. In the Na+ media, acidotic rat kidneys produced 2.6 times more NH4+ and utilized 1.5-fold more glutamine than their NA counterparts. In the choline media, acidotic rat kidneys had a large drop in NH4+ production but not in glutamine utilization; associated with this was a large glutamate accumulation in the extracellular compartments consistent with flow through the extracellular pathway. To demonstrate the applicability of this model, the role of the adrenals and glucocorticoids in modulating fluxes over these pathways was studied. Kidneys from adrenalectomized acidotic rats exhibited a diminished transport of glutamine, reduced utilization and decreased ammoniagenesis; glutamate accumulation in the extracellular compartment rose consistent with greater flux via the extracellular glutaminase. Supplementing these animals with triamcinolone restored flow into the cellular pathway. The results confirm the in situ activity of two renal glutaminases whose relative contributions to renal ammoniagenesis are dependent on the acid base balance, glucocorticoids, and the existing Na+ gradient.

Role of dactinomycin in the improved survival of children with Wilms' tumor

JAMA ◽  
1966 ◽  
Vol 195 (12) ◽  
pp. 1005-1009 ◽  
Author(s):  
D. J. Fernbach
Keyword(s):  
Wilms Tumor

Role of the allergist in diagnosis and management of patients with uveitis

JAMA ◽  
1966 ◽  
Vol 195 (3) ◽  
pp. 167-172 ◽  
Author(s):  
T. E. Van Metre
Keyword(s):  
Diagnosis And Management

The power of norms to sway fused group members

2018 ◽  
Vol 41 ◽  
Author(s):  
Winnifred R. Louis ◽  
Craig McGarty ◽  
Emma F. Thomas ◽  
Catherine E. Amiot ◽  
Fathali M. Moghaddam
Keyword(s):  
Evolutionary Anthropology ◽  
Normative Systems ◽  
Violent Extremism ◽  
Identity Fusion ◽  
Group Members

AbstractWhitehouse adapts insights from evolutionary anthropology to interpret extreme self-sacrifice through the concept of identity fusion. The model neglects the role of normative systems in shaping behaviors, especially in relation to violent extremism. In peaceful groups, increasing fusion will actually decrease extremism. Groups collectively appraise threats and opportunities, actively debate action options, and rarely choose violence toward self or others.

Elaborating the role of reflection and individual differences in the study of folk-economic beliefs

2018 ◽  
Vol 41 ◽  
Author(s):  
Kevin Arceneaux
Keyword(s):  
Decision Making ◽  
Individual Differences ◽  
Cognitive Processes ◽  
Evolutionary History ◽  
Behavioral Responses ◽  
History Of ◽  
Economic Beliefs

AbstractIntuitions guide decision-making, and looking to the evolutionary history of humans illuminates why some behavioral responses are more intuitive than others. Yet a place remains for cognitive processes to second-guess intuitive responses – that is, to be reflective – and individual differences abound in automatic, intuitive processing as well.

The role of affect in feelings of obligation

2020 ◽  
Vol 43 ◽  
Author(s):  
Stefen Beeler-Duden ◽  
Meltem Yucel ◽  
Amrisha Vaish
Keyword(s):  
Positive Emotions ◽  
The Creation ◽  
Sense Of Obligation

Abstract Tomasello offers a compelling account of the emergence of humans’ sense of obligation. We suggest that more needs to be said about the role of affect in the creation of obligations. We also argue that positive emotions such as gratitude evolved to encourage individuals to fulfill cooperative obligations without the negative quality that Tomasello proposes is inherent in obligations.

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