Effect of altered acid-base balance and of various agonists on levels of renal glutamate dehydrogenase mRNA

Kaiser, S.; Hwang, Jungho; Smith, Hillary M.; Banner, Carl; Welbourne, T. C.; Curthoys, Norman P.

doi:10.1152/ajprenal.1992.262.3.f507

Cited by 14 publications

(9 citation statements)

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“…Furthermore, identification of these regulatory elements should aid in understanding the GDH expression in other organs, e.g. the expression in kidney which is increased in metabolic acidosis [66] or the reduced expression that may be associated with certain neurodegenerative diseases [47,67]. The isolation and characterization of the GDH gene, as reported in this paper, is a first step in the study of the primary processes involved in GDH expression.…”

Section: Tata Box and Is Very G + C-richmentioning

confidence: 97%

Isolation and characterization of the rat gene encoding glutamate dehydrogenase

Das

Arnberg

Malingré

et al. 1993

European Journal of Biochemistry

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The concentration of glutamate dehydrogenase (GDH) varies strongly between different organs and between different regions within organs. To permit further studies on the regulation of GDH expression, we isolated and characterized the rat gene encoding the GDH protein. This gene contains 13 exons and spans approximately 34 kbp. The GDH gene is present as a single, autosomally located copy in the Wistar rat genome, but shows an extensive restriction-fragment-length polymorphism for several enzymes. Promoter activity of the 5'-flanking sequence is shown by transient transfection experiments. The 5'-flanking sequence contains a TTAAAA sequence at position -29, instead of a consensus TATA box and, like many other TATA-less promoters, is characterized by a very high G + C content. In addition, consensus sequences for the binding sites of the transcription factors Spl and Zif268 are present in the G + C-rich upstream region.Glutamate dehydrogenase (GDH), a mitochondria1 matrix enzyme, catalyzes the reversible oxidative deamination of L-glutamate to 2-oxoglutarate and ammonia, using NAD' or NADP' as cofactor [l]. GDH therefore plays an important role in ammonia and amino acid metabolism. Although GDH is an ubiquitous enzyme, its concentration in different organs varies markedly, the highest concentrations being found in liver, brain, kidney and pancreas [2, 31.In liver GDH is highly expressed only in the hepatocytes. In the adult rat [4-91 and human [lo] liver the GDH concentration depends on the position of the hepatocyte along the central-portal distance, the highest activity and protein concentration being found in hepatocytes around the central veins. In rat liver two mRNAs are present which differ in the length of their 3'-untranslated region [ l l , 121. As shown by in situ hybridization, these mRNAs are also heterogeneously distributed within the adult rat liver, both showing a gradient in cellular concentration decreasing along the central-portal distance [13]. The heterogeneous mRNA distribution in the liver lobule demonstrates the presence of regional differences in the rate of pretranslational processes involved in GDH

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Section: Tata Box and Is Very G + C-richmentioning

confidence: 97%

Isolation and characterization of the rat gene encoding glutamate dehydrogenase

Das

Arnberg

Malingré

et al. 1993

European Journal of Biochemistry

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“…This decrease in α-KG both accelerates GDH activity, by relieving α-KG-mediated competitive inhibition of the enzymatic reaction, and it inhibits the reverse reaction (136, 137). The increased mRNA expression appears related to increased mRNA stability, not transcription (75). Four AU-rich elements are present in the 3′-UTR, bind ζ-cystallin and appear to confer pH-responsive stabilization of GDH mRNA (138).…”

Section: Specific Proteins Involved In Renal Ammonia Metabolismmentioning

confidence: 99%

Renal Ammonia Metabolism and Transport

Weiner

Verlander

2013

Comprehensive Physiology

156

136

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Renal ammonia metabolism and transport mediates a central role in acid-base homeostasis. In contrast to most renal solutes, the majority of renal ammonia excretion derives from intrarenal production, not from glomerular filtration. Renal ammoniagenesis predominantly results from glutamine metabolism, which produces 2 NH4+ and 2 HCO3− for each glutamine metabolized. The proximal tubule is the primary site for ammoniagenesis, but there is evidence for ammoniagenesis by most renal epithelial cells. Ammonia produced in the kidney is either excreted into the urine or returned to the systemic circulation through the renal veins. Ammonia excreted in the urine promotes acid excretion; ammonia returned to the systemic circulation is metabolized in the liver in a HCO3−-consuming process, resulting in no net benefit to acid-base homeostasis. Highly regulated ammonia transport by renal epithelial cells determines the proportion of ammonia excreted in the urine versus returned to the systemic circulation. The traditional paradigm of ammonia transport involving passive NH3 diffusion, protonation in the lumen and NH4+ trapping due to an inability to cross plasma membranes is being replaced by the recognition of limited plasma membrane NH3 permeability in combination with the presence of specific NH3-transporting and NH4+-transporting proteins in specific renal epithelial cells. Ammonia production and transport are regulated by a variety of factors, including extracellular pH and K+, and by several hormones, such as mineralocorticoids, glucocorticoids and angiotensin II. This coordinated process of regulated ammonia production and transport is critical for the effective maintenance of acid-base homeostasis.

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“…The mechanism (the stimulation of the rate of transcription or stabilization of the mRNAs) responsible for the increased glutamate dehydrogenase and glucose-6-phosphatase mRNA levels that we observed merits further study. In this respect, it should be mentioned that experiments performed in rats in i o, and with LLC-PK-F + cells, indicates that changes in renal glutamate dehydrogenase mRNA levels in response to metabolic acidosis result from stabilization of these mRNAs [28].…”

Section: Regulatory Steps Of Glutamine Metabolism and Adaptation To Smentioning

confidence: 99%

Effect of starvation on glutamine ammoniagenesis and gluconeogenesis in isolated mouse kidney tubules

Conjard

Brun

Martin

et al. 2002

Biochemical Journal

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It has been shown recently that glutamine is taken up by the mouse kidney in vivo. However, knowledge about the fate of this amino acid and the regulation of its metabolism in the mouse kidney remains poor. Given the physiological and pathophysiological importance of renal glutamine metabolism and the increasing use of genetically modified mice in biological research, we have conducted a study to characterize glutamine metabolism in the mouse kidney. Proximal tubules isolated from fed and 48 h-starved mice and then incubated with a physiological concentration of glutamine, removed this amino acid and produced ammonium ions at similar rates. In agreement with this observation, activities of the ammoniagenic enzymes, glutaminase and glutamate dehydrogenase, were not different in the renal cortex of fed and starved mice, but the glutamate dehydrogenase mRNA level was elevated 4.5-fold in the renal cortex from starved mice. In contrast, glucose production from glutamine was greatly stimulated whereas the glutamine carbon removed, that was presumably completely oxidized in tubules from fed mice, was virtually suppressed in tubules from starved animals. In accordance with the starvation-induced stimulation of glutamine gluconeogenesis, the activities and mRNA levels of glucose-6-phosphatase, and especially of phosphoenolpyruvate carboxykinase, but not of fructose-1,6-bisphosphatase, were increased in the renal cortex of starved mice. On the basis of our in vitro results, the elevated urinary excretion of ammonium ions observed in starved mice probably reflected an increased transport of these ions into the urine at the expense of those released into the renal veins rather than a stimulation of renal ammoniagenesis.

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Effect of altered acid-base balance and of various agonists on levels of renal glutamate dehydrogenase mRNA

Cited by 14 publications

References 0 publications

Isolation and characterization of the rat gene encoding glutamate dehydrogenase

Isolation and characterization of the rat gene encoding glutamate dehydrogenase

Renal Ammonia Metabolism and Transport

Effect of starvation on glutamine ammoniagenesis and gluconeogenesis in isolated mouse kidney tubules

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