Regulation of mitochondrial glutamine/glutamate metabolism by glutamate transport: studies with 15N

2001 ◽  
Vol 280 (5) ◽  
pp. C1151-C1159 ◽  
Author(s):  
Tomas Welbourne ◽  
Itzhak Nissim

We focused on the role of plasma membrane glutamate uptake in modulating the intracellular glutaminase (GA) and glutamate dehydrogenase (GDH) flux and in determining the fate of the intracellular glutamate in the proximal tubule-like LLC-PK1-F+ cell line. We used high-affinity glutamate transport inhibitors d-aspartate (d-Asp) and dl-threo-β-hydroxyaspartate (THA) to block extracellular uptake and then used [15N]glutamate or [2-15N]glutamine to follow the metabolic fate and distribution of glutamine and glutamate. In monolayers incubated with [2-15N]glutamine (99 atom %excess), glutamine and glutamate equilibrated throughout the intra- and extracellular compartments. In the presence of 5 mMd-Asp and 0.5 mM THA, glutamine distribution remained unchanged, but the intracellular glutamate enrichment decreased by 33% ( P < 0.05) as the extracellular enrichment increased by 39% ( P < 0.005). With glutamate uptake blocked, intracellular glutamate concentration decreased by 37% ( P < 0.0001), in contrast to intracellular glutamine concentration, which remained unchanged. Both glutamine disappearance from the media and the estimated intracellular GA flux increased with the fall in the intracellular glutamate concentration. The labeled glutamate and NH[Formula: see text] formed from [2-15N]glutamine and recovered in the media increased 12- and 3-fold, respectively, consistent with accelerated GA and GDH flux. However, labeled alanine formation was reduced by 37%, indicating inhibition of transamination. Although both d-Asp and THA alone accelerated the GA and GDH flux, only THA inhibited transamination. These results are consistent with glutamate transport both regulating and being regulated by glutamine and glutamate metabolism in epithelial cells.

2006 ◽  
Vol 291 (4) ◽  
pp. C618-C626 ◽  
Author(s):  
Fabrice Porcheray ◽  
Cathie Léone ◽  
Boubekeur Samah ◽  
Anne-Cécile Rimaniol ◽  
Nathalie Dereuddre-Bosquet ◽  
...  

Central nervous system disorders are still a common complication of human immunodeficiency virus (HIV) infection and can lead to dementia and death. They are mostly the consequences of an inflammatory macrophagic activation and relate to glutamate-mediated excitotoxicity. However, recent studies also suggest neuroprotective aspects of macrophage activation through the expression of glutamate transporters and glutamine synthetase. We thus aimed to study whether HIV infection or activation of macrophages could modulate glutamate metabolism in these cells. We assessed the effect of HIV infection on glutamate transporter expression as well as on glutamate uptake by macrophages and showed that glutamate transport was partially decreased in the course of virus replication, whereas excitatory amino acid transporter-2 (EAAT-2) gene expression was dramatically increased. The consequences of HIV infection on glutamine synthetase were also measured and for the first time we show the functional expression of this key enzyme in macrophages. This expression was repressed during virus production. We then quantified EAAT-1 and EAAT-2 gene expression as well as glutamate uptake in differentially activated macrophages and show that the effects of HIV are not directly related to pro- or anti-inflammatory mediators. Finally, this study shows that glutamate transport by macrophages is less affected than what has been described in astrocytes. Macrophages may thus play a role in neuroprotection against glutamate in the infected brain, through their expression of both EAATs and glutamine synthetase. Because glutamate metabolism by activated macrophages is sensitive to both HIV infection and inflammation, it may thus be of potential interest as a therapeutic target in HIV encephalitis.


2021 ◽  
pp. 1-22
Author(s):  
Jiayi Song ◽  
Xuehan Yang ◽  
Ming Zhang ◽  
Chunyan Wang ◽  
Li Chen

Glutamate is the main excitatory neurotransmitter in the brain, and its excitatory neurotoxicity is closely related to the occurrence and development of Alzheimer’s disease. However, increasing evidence shows that in the process of Alzheimer’s disease, glutamate is not only limited to its excitotoxicity as a neurotransmitter but also related to the disorder of its metabolic balance. The balance of glutamate metabolism in the brain is an important determinant of central nervous system health, and the maintenance of this balance is closely related to glutamate uptake, glutamate circulation, intracellular mitochondrial transport, and mitochondrial metabolism. In this paper, we intend to elaborate the key role of mitochondrial glutamate metabolism in the pathogenesis of Alzheimer’s disease and review glutamate metabolism in mitochondria as a potential target in the treatment of Alzheimer’s disease.


2002 ◽  
Vol 87 (6) ◽  
pp. 3165-3168 ◽  
Author(s):  
Jeannie Chin ◽  
John A. Burdohan ◽  
Arnold Eskin ◽  
John H. Byrne

Aplysia sensory neurons possess high-affinity glutamate uptake activity that is regulated by serotonin. To gain insight into the physiological role of glutamate uptake in sensory neurons, we examined whether blockade of glutamate transport altered synaptic transmission. We also examined whether glutamate transport affected homosynaptic depression and posttetanic potentiation (PTP). In the presence of dl-threo-β-hydroxyaspartic acid (THA), previously shown to block glutamate uptake in Aplysia, the duration of unitary excitatory postsynaptic potentials (EPSPs) was significantly increased and their amplitude was significantly reduced. Similar effects were observed in the properties of summated EPSPs. However, no effect on the induction of homosynaptic depression or PTP was observed. Although it is unclear whether THA exerted its effect by modulating neuronal and/or glial mechanisms, at least one target of THA was neuronal, as the duration of unitary EPSPs measured in cultured sensorimotor synapses was also increased in the presence of THA. These results support the hypotheses that glutamate is the transmitter released by the sensory neurons and that glutamate transport plays an important role in regulating features of synaptic transmission in Aplysia.


2021 ◽  
pp. 104-109
Author(s):  
Chernysh O.O.

The urgency of the researched problem is connected with the growing role of mass media in modern conditions leads to change of values and transformation of identity of the person. The active growth of the role of the media, their influence on the formation and development of personality leads to the concept of “media socialization” and immutation in the media. The aim of the study is to outline the possibilities of the process of media socialization in the context of immutation in the media. The methods of our research are: analysis of pedagogical, psychological, literature, synthesis, comparison, generalization. The article analyzes the views of domestic and foreign scientists on the problem of immutation in the media and the transformation of the information space. In the context of the mass nature of the immutation of society, the concept of “media socialization” becomes relevant, which is the basis for reducing the negative impact of the media on the individual.The author identifies the lack of a thorough study of the concept of “media socialization” in modern scientific thought. Thus, media socialization is associated with the transformation of traditional means of socialization, and is to assimilate and reproduce the social experience of mankind with the help of new media.The article analyzes the essence of the concepts “media space”, “mass media” and “immutation”. The influence of mass media on the formation and development of the modern personality is described in detail.The study concluded that it is necessary to form a media culture of the individual, to establish safe and effective interaction of young people with the modern media system, the formation of media awareness, media literacy and media competence in accordance with age and individual characteristics for successful media socialization. The role of state bodies in solving the problem of media socialization of the individual was also determined. It is determined that the process of formation of media culture in youth should take place at the level of traditional institutions of socialization of the individual.The author sees the prospect of further research in a detailed analysis and study of the potential of educational institutions as an institution and a means of counteracting the mass nature of the immutation of society.Key words: immutation, media socialization, mass media, media space, information.


2012 ◽  
Vol 21 (2) ◽  
pp. 223-243
Author(s):  
Irit Degani-Raz

The idea that Beckett investigates in his works the limits of the media he uses has been widely discussed. In this article I examine the fiction Imagination Dead Imagine as a limiting case in Beckett's exploration of limits at large and the limits of the media he uses in particular. Imagination Dead Imagine is shown to be the self-reflexive act of an artist who imaginatively explores the limits of that ultimate medium – the artist's imagination itself. My central aim is to show that various types of structural homologies (at several levels of abstraction) can be discerned between this poetic exploration of the limits of imagination and Cartesian thought. The homologies indicated here transcend what might be termed as ‘Cartesian typical topics’ (such as the mind-body dualism, the cogito, rationalism versus empiricism, etc.). The most important homologies that are indicated here are those existing between the role of imagination in Descartes' thought - an issue that until only a few decades ago was quite neglected, even by Cartesian scholars - and Beckett's perception of imagination. I suggest the use of these homologies as a tool for tracing possible sources of inspiration for Beckett's Imagination Dead Imagine.


Author(s):  
Erwin Erwin ◽  
Nasarudin Nasarudin ◽  
Husnan Husnan

The purpose of this research is to explain the importance of the student organizations and describe their efforts to improve the speaking skills of students at the Mahad Khalid Bin Al Waleed at the University of Muhammadiyah Mataram. This research uses the qualitative approach with the descriptive type. The result shows the student organizations play an important role based on their objectives and functions. The objectives are to help the foundation and all parties in the Ma'had develop the students’ potential and qualification, and to be the place for the students to share their problems and complaints, while the functions are as one of the media to develop students’ quality, both the members of the non-member, and as the good examples and pioneers of any good deeds. The efforts done by student organizations in improving speaking skills are such as by making activities that lead to improving students' speaking skills like sticking vocabularies in each class and Friday activities such as language game, Arabic debate and short lecture.


2020 ◽  
pp. 97-110
Author(s):  
E. N. Mikhailova ◽  
V. A. Telegina

The article is devoted to the study of evaluative tools used in modern French media in order to form the media image of a representative of the political elite. The techniques used in the creation of a memorial media portrait of Jacques Chirac (1932—2019), President of France from 1995 to 2007 are considered. The research material was the most prestigious French print media of various political orientations, published in late September — early October 2019 in connection with the death of the ex-President of the French Republic. The relevance of the research topic is dictated by the close attention of modern linguistics to axiological phenomena, differently presented in different types of discursive practices. The novelty of the study is due to the appeal to the analysis of the complex of evaluation tools used in the French print media when characterizing the former leader of the state during the nation’s farewell period. The estimated potential of the title of the article and its influence on the formation of the estimated vector of the entire text of the publication are shown. A systematic analysis of the assessment expression means, reflected in the memorial media portrait of the politician, is given. The factors that influenced the peculiarities of their use in this type of media portrait are revealed.


2016 ◽  
Vol 2 (2) ◽  
pp. 40
Author(s):  
Miriam Aparicio

This study tests some hypotheses included in the psycho-social-communicational paradigm, which emphasizes the cognitive effects of the media and the role of the psychosocial subject as the recipient


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