scholarly journals Transcriptional regulation by glucocorticoids of mitochondrial oxidative enzyme genes in the developing rat kidney

1996 ◽  
Vol 315 (2) ◽  
pp. 555-562 ◽  
Author(s):  
Fatima DJOUADI ◽  
Jean BASTIN ◽  
Daniel P. KELLY ◽  
Claudie MERLET-BENICHOU
Keyword(s):  
Fatty Acid ◽  
Molecular Mechanisms ◽  
Tricarboxylic Acid Cycle ◽  
Rat Kidney ◽  
Kidney Cortex ◽  
Transcriptional Level ◽  
Mitochondrial Enzymes ◽  
Mrna Levels ◽  
Rat Kidney Cortex ◽  
Mitochondrial Fatty Acid

Mitochondrial fatty acid β-oxidation plays a major role in providing the ATP required for reabsorptive processes in the adult rat kidney. However, the molecular mechanisms and signals involved in induction of the enzymes of fatty acid oxidation during development in this and other organs are unknown. We therefore studied the changes in the steady-state levels of mRNA encoding medium-chain acyl-CoA dehydrogenase (MCAD), which catalyses the initial step in mitochondrial fatty acid β-oxidation, in the rat kidney cortex and medulla between postnatal days 10 and 30. Furthermore, we investigated whether the expression of MCAD and of mitochondrial malate dehydrogenase (mMDH), a key enzyme in the tricarboxylic acid cycle, might be co-ordinately regulated by circulating glucocorticoids in the immature kidney during development. In the cortex, the levels of MCAD mRNA rose 4-fold between day 10 and day 21, and then decreased from day 21 to day 30. In the medulla a postnatal increase in the concentration of MCAD mRNA (8-fold) was observed during the same period. Adrenalectomy prevented the 16–21-day developmental increases in MCAD and mMDH mRNA levels in the cortex and medulla; these could be restored by dexamethasone treatment. A single injection of dexamethasone into 10-day-old rats led to a rise in MCAD and mMDH mRNA levels in the renal cortex due to stimulation of gene transcription, as shown by nuclear run-on assays. Therefore MCAD and mMDH gene expression is tightly regulated at the transcriptional level by developmental changes in circulating glucocorticoid levels. These hormones might thus represent a good candidate as a co-ordinating factor in the expression of nuclear genes encoding mitochondrial enzymes in the kidney during postnatal development.

Changes in mRNAs for enzymes of glutamine metabolism in kidney and liver during ammonium chloride acidosis

1994 ◽  
Vol 267 (3) ◽  
pp. F400-F406 ◽  
Author(s):  
A. C. Schoolwerth ◽  
P. A. deBoer ◽  
A. F. Moorman ◽  
W. H. Lamers
Keyword(s):  
Phosphoenolpyruvate Carboxykinase ◽  
Rat Kidney ◽  
Glutamine Metabolism ◽  
Kidney Cortex ◽  
Mrna Levels ◽  
Rat Kidney Cortex ◽  
Physiological Conditions ◽  
Glutamine Synthase ◽  
Sustained Increase

Changes in protein and mRNAs for enzymes of glutamine metabolism were determined in rat kidney cortex at different times after induction of NH4Cl acidosis. After NH4Cl, phosphoenolpyruvate carboxykinase (PEPCK) mRNA increased 16-fold by 10 h (P < 0.05) and then returned to control levels by 30 h. In situ hybridization (ISH) showed that PEPCK mRNA was confined to medullary rays; after NH4Cl, expression of PEPCK expanded throughout the cortex, reaching a maximal intensity at 10 h. Phosphate-dependent glutaminase (PDG) and glutamate dehydrogenase (GDH) mRNAs increased 8- and 2.6-fold, respectively (both P < 0.05), by 10 h before decreasing; the increased expression was confirmed by ISH. Immunohistochemistry showed that increased PEPCK, PDG, and GDH protein occurred at variable times after the rise in mRNAs. The increase was confined to proximal tubules and was sustained, a finding noted also by Western blot analysis. In contrast, glutamine synthase protein and mRNA, confined to deep cortex and outer medullar, did not change after NH4Cl. These studies reveal striking changes in PEPCK and PDG mRNAs in rat renal cortex during acidosis. The ISH pattern suggested that increased amounts of PEPCK were synthesized in recruited cells which contained little enzyme under physiological conditions. mRNA levels for PEPCK, PDG, and GDH peaked at 10 h before returning to control levels. Despite the decrease in mRNAs, a sustained increase in proteins was noted.

Fatty acid inducible cytochrome P-454 of rat kidney cortex microsomes

1970 ◽  
Vol 39 (6) ◽  
pp. 1073-1080 ◽  
Author(s):  
Sten Jakobsson ◽  
Hjördis Thor ◽  
Sten Orrenius
Keyword(s):  
Fatty Acid ◽  
Rat Kidney ◽  
Kidney Cortex ◽  
Rat Kidney Cortex

Effect of bicarbonate on glutamine and glutamate metabolism by rat kidney cortex mitochondria

1985 ◽  
Vol 249 (4) ◽  
pp. F573-F581
Author(s):  
R. C. Scaduto ◽  
A. C. Schoolwerth
Keyword(s):  
Rat Kidney ◽  
Competitive Inhibitor ◽  
Kidney Cortex ◽  
Mitochondrial Enzymes ◽  
Glutamate Metabolism ◽  
Bicarbonate Buffer ◽  
Rat Kidney Cortex ◽  
Glutamate Oxalacetate Transaminase ◽  
Stimulation Of

Isolated rat kidney cortex mitochondria were incubated at pH 7.4 in the presence or absence of a CO2/bicarbonate buffer (28 mM) to investigate the pH-independent role of bicarbonate on glutamine and glutamate metabolism. Changes in the concentration of key intermediates and products during the incubations were used to calculate metabolite flux rates through specific mitochondrial enzymes. With 1 mM glutamine and 2 mM glutamate as substrates, bicarbonate caused an inhibition of glutamate oxalacetate transaminase flux and a stimulation of glutamate deamination. The same effects were also produced with addition of either aminooxyacetate or malonate. These effects of bicarbonate were prevented when 0.2 mM malate was included as an additional substrate. Bicarbonate ion was identified as a potent competitive inhibitor of rat kidney cortex succinate dehydrogenase. These results indicate that aminooxyacetate, malonate, and bicarbonate all act to stimulate glutamate deamination through a suppression of glutamate transamination, and that the control by transamination of glutamate deamination is due to alterations in alpha-ketoglutarate metabolism. In contrast, in mitochondria incubated with glutamine in the absence of glutamate, bicarbonate was found to inhibit glutamate dehydrogenase flux. This effect was found to be due in part to the lower intramitochondrial pH observed in incubations with bicarbonate. These findings indicate that bicarbonate ion, independent of pH, may have an important regulatory role in renal glutamine and glutamate metabolism.

scholarly journals PPARα Gene Expression in the Developing Rat Kidney: Role of Glucocorticoids

2001 ◽  
Vol 12 (6) ◽  
pp. 1197-1203
Author(s):  
FATIMA DJOUADI ◽  
JEAN BASTIN
Keyword(s):  
Gene Expression ◽  
Fatty Acids ◽  
Fatty Acid ◽  
Culture Media ◽  
Rat Kidney ◽  
Fold Increase ◽  
Kidney Cortex ◽  
Peroxisome Proliferator ◽  
Rat Kidney Cortex

Abstract. The α isoform of peroxisome proliferator-activated receptor (PPARα), which is highly expressed in the kidney, can stimulate the expression of genes that are involved in fatty acid catabolism and therefore might be involved in the control of renal fatty acid β-oxidation. PPARα expression and its regulation in the immature kidney are not well documented. This study delineated the developmental pattern of PPARα expression in the rat kidney cortex and the medulla between postnatal days 10 and 30 and investigated the role of glucocorticoids in regulating PPARα expression. In the cortex, PPARα mRNA and protein increased 2- and 1.8-fold, respectively, from 10 to 21 d and then decreased 1.5- and 2.4-fold from 21 to 30 d. In the medulla, PPARα mRNA and protein increased continuously 3.3- and 2.4-fold, respectively. It is shown here that acute treatment by dexamethasone of 10-d-old rats precociously induced a 4- to 6-fold increase in PPARα mRNA and a 1.8-fold increase in protein within 6 h in each part of the kidney. Chronic injection of dexamethasone for 3 d also increased PPARα mRNA 3.8- and 2.2-fold in the cortex and the medulla, respectively, with a 1.5- and 2-fold increase in protein. Furthermore, adrenalectomy prevented the increases in PPARα mRNA and protein in both the cortex and the medulla between postnatal days 16 and 21, and these could be restored by dexamethasone treatment. Finally, with the use of an established renal cell line, it was shown that glucocorticoids stimulate gene expression of PPARα and of medium chain acyl-CoA dehydrogenase (MCAD, a PPARα target gene) 2- to 4-fold and 1.5-fold, respectively, and that addition of fatty acids in the culture media led to a 2.2-fold increase in MCAD mRNA. Altogether, these results demonstrated that glucocorticoids are potent regulators of PPARα development in the immature kidney and that these hormones act in concert with fatty acids to regulate MCAD gene expression in renal cells.

Cytochrome P450K of rat kidney cortex microsomes: Its Involvement in fatty acid ω- and (ω-1)-hydroxylation

1972 ◽  
Vol 150 (1) ◽  
pp. 64-71 ◽  
Author(s):  
Åke Ellin ◽  
Sten V. Jakobsson ◽  
John B. Schenkman ◽  
Sten Orrenius
Keyword(s):  
Fatty Acid ◽  
Rat Kidney ◽  
Kidney Cortex ◽  
Rat Kidney Cortex

Effect of metal ions on in vitro gluconeogenesis in rat kidney cortex slices

1965 ◽  
Vol 208 (5) ◽  
pp. 841-846 ◽  
Author(s):  
Julia Z. Rutman ◽  
Lawrence E. Meltzer ◽  
J. Roderick Kitchell ◽  
Robert J. Rutman ◽  
Philip George
Keyword(s):  
Amino Acids ◽  
Metal Ions ◽  
Tricarboxylic Acid Cycle ◽  
Rat Kidney ◽  
Kidney Cortex ◽  
Rat Kidney Cortex ◽  
In Vitro Systems ◽  
Cortex Slices ◽  
Kidney Cortex Slices

The effect of metal ions on glucose formation from amino acids and glycolytic and tricarboxylic acid cycle intermediates has been examined in rat kidney cortex slices in vitro. Of the metals tested, only Mn++ and Ca++ have been shown to be stimulatory, while Zn++, Cu++, and Cd++ are inhibitory. The case of Mn++ activation is of particular interest because Mg++ ions are inactive in this system, despite the similarities usually observed in the in vitro systems. The stimulation of gluconeogenesis from α-keto acids is comparable for both Ca++ and Mn++, in contrast to the lack of a Mn++ effect with the homologous l-α-amino acids. Evidence is presented as to the possible significance of metal ions in regulating carbohydrate metabolism.

scholarly journals Gluconeogenesis in the kidney cortex. Effects of d-malate and amino-oxyacetate

1970 ◽  
Vol 116 (3) ◽  
pp. 483-491 ◽  
Author(s):  
R. Rognstad ◽  
J. Katz
Keyword(s):  
Malate Dehydrogenase ◽  
High Speed ◽  
Tricarboxylic Acid Cycle ◽  
Rat Kidney ◽  
Supernatant Fraction ◽  
Kidney Cortex ◽  
Rat Kidney Cortex ◽  
High Concentrations ◽  
Cortex Slices ◽  
Kidney Cortex Slices

1. Rat kidney-cortex slices incubated with d-malate alone formed very little glucose. d-Malate, however, augmented gluconeogenesis from l-lactate and inhibited gluconeogenesis from pyruvate and l-malate. 2. d-Malate had little effect on the rate of the tricarboxylic acid cycle with or without other substrates added. 3. d-Malate inhibited the activity of the l-malate dehydrogenase in a high-speed-supernatant fraction from kidney cortex. 4. It was concluded that d-malate inhibited either the operation of the cytoplasmic l-malate dehydrogenase or malate outflow from the mitochondria in the intact kidney-cortex cell. This supports the hypothesis of Lardy, Paetkau & Walter (1965) and Krebs, Gascoyne & Notton (1967) on the role of malate as carrier for carbon and reducing equivalents in gluconeogenesis. 5. Gluconeogenesis from l-lactate in kidney-cortex slices was strongly inhibited by a low concentration (0.1mm) of amino-oxyacetate, whereas glucose formation from pyruvate, malate, aspartate and several other compounds was only slightly affected. 6. High concentrations of l-aspartate largely reversed the inhibition of gluconeogenesis from l-lactate caused by amino-oxyacetate. 7. Amino-oxyacetate inhibited strongly the glutamate–oxaloacetate transaminase in the 30000g supernatant fraction of a kidney-cortex homogenate. The presence of l-aspartate decreased the inhibition of the transaminase by amino-oxyacetate. 8. Detritiation of l-[2-3H]aspartate was inhibited by 90% during an incubation of kidney-cortex slices with l-lactate and amino-oxyacetate. 9. Low concentrations (10μm) of artificial electron acceptors such as Methylene Blue and phenazine methosulphate abolished most of the inhibition of gluconeogenesis from l-lactate by amino-oxyacetate. This is interpreted as an activation of net malate outflow from the mitochondria by-passing the inhibited transfer of oxaloacetate. 10. These findings support the concept that transamination to aspartate is involved in the transfer of oxaloacetate from mitochondria to cytosol required in gluconeogenesis from l-lactate.

scholarly journals Adipokines and Metabolic Regulators in Human and Experimental Pulmonary Arterial Hypertension

2021 ◽  
Vol 22 (3) ◽  
pp. 1435
Author(s):  
Aimilia Papathanasiou ◽  
Fotios Spyropoulos ◽  
Zoe Michael ◽  
Kyoung Joung ◽  
Despina Briana ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Adipose Tissue ◽  
Fatty Acid ◽  
Tricarboxylic Acid Cycle ◽  
Fibroblast Growth Factor 21 ◽  
Mrna Levels ◽  
Rodent Models ◽  
Fatty Acid Binding ◽  
Metabolic Regulators ◽  
Circulating Levels

Pulmonary hypertension (PH) is associated with meta-inflammation related to obesity but the role of adipose tissue in PH pathogenesis is unknown. We hypothesized that adipose tissue-derived metabolic regulators are altered in human and experimental PH. We measured circulating levels of fatty acid binding protein 4 (FABP-4), fibroblast growth factor -21 (FGF-21), adiponectin, and the mRNA levels of FABP-4, FGF-21, and peroxisome proliferator-activated receptor γ (PPARγ) in lung tissue of patients with idiopathic PH and healthy controls. We also evaluated lung and adipose tissue expression of these mediators in the three most commonly used experimental rodent models of pulmonary hypertension. Circulating levels of FABP-4, FGF-21, and adiponectin were significantly elevated in PH patients compared to controls and the mRNA levels of these regulators and PPARγ were also significantly increased in human PH lungs and in the lungs of rats with experimental PH compared to controls. These findings were coupled with increased levels of adipose tissue mRNA of genes related to glucose uptake, glycolysis, tricarboxylic acid cycle, and fatty acid oxidation in experimental PH. Our results support that metabolic alterations in human PH are recapitulated in rodent models of the disease and suggest that adipose tissue may contribute to PH pathogenesis.

scholarly journals Increase of Na/Pi-cotransport encoding mRNA in response to low Pi diet in rat kidney cortex.

1994 ◽  
Vol 269 (9) ◽  
pp. 6637-6639
Author(s):  
A. Werner ◽  
S.A. Kempson ◽  
J. Biber ◽  
H. Murer
Keyword(s):  
Rat Kidney ◽  
Kidney Cortex ◽  
Rat Kidney Cortex
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