DDT-Induced Stimulation of Key Gluconeogenic Enzymes In Rat Kidney Cortex

1972 ◽  
Vol 50 (2) ◽  
pp. 225-229 ◽  
Author(s):  
S. Kacew ◽  
R. L. Singhal ◽  
G. M. Ling
Keyword(s):  
Pyruvate Carboxylase ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Rat Kidney ◽  
Kidney Cortex ◽  
Glucocorticoid Hormones ◽  
Rat Kidney Cortex ◽  
Gluconeogenic Enzymes ◽  
Maximal Stimulation ◽  
Adrenalectomized Rats ◽  
Stimulation Of

Administration of technical DDT or o,p′-DDT produced marked increases in pyruvate carboxylase, phosphoenolpyruvate carboxykinase, fructose-1,6-diphosphatase, and glueose-6-phospfaatase activities in rat kidney cortex. Significant increases in these key gluconeogenic enzymes occurred at 2–3 days and maximal stimulation was seen 5–7 days after the beginning of o,p′-DDT treatment. This DDT isomer, when given to adrenalectomized rats, produced increases in renal enzymes similar to those observed in intact animals. Furthermore, since administration of triamcinolone to o,p′-DDT-treated rats failed to potentiate the action of this insecticide on various enzymes, evidence indicates that the stimulation of kidney cortex gluconeogenesis by DDT is not mediated through a release of glucocorticoid hormones from the adrenal cortex.

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.

scholarly journals Proteomic profiling and pathway analysis of the response of rat renal proximal convoluted tubules to metabolic acidosis

2013 ◽  
Vol 305 (5) ◽  
pp. F628-F640 ◽  
Author(s):  
Kevin L. Schauer ◽  
Dana M. Freund ◽  
Jessica E. Prenni ◽  
Norman P. Curthoys
Keyword(s):  
Metabolic Acidosis ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Pathological Condition ◽  
Rat Kidney ◽  
Proximal Convoluted Tubule ◽  
Kidney Cortex ◽  
Combined Processes ◽  
Proteomic Profiling ◽  
Rat Kidney Cortex ◽  
Cytosolic Proteins

Metabolic acidosis is a relatively common pathological condition that is defined as a decrease in blood pH and bicarbonate concentration. The renal proximal convoluted tubule responds to this condition by increasing the extraction of plasma glutamine and activating ammoniagenesis and gluconeogenesis. The combined processes increase the excretion of acid and produce bicarbonate ions that are added to the blood to partially restore acid-base homeostasis. Only a few cytosolic proteins, such as phosphoenolpyruvate carboxykinase, have been determined to play a role in the renal response to metabolic acidosis. Therefore, further analysis was performed to better characterize the response of the cytosolic proteome. Proximal convoluted tubule cells were isolated from rat kidney cortex at various times after onset of acidosis and fractionated to separate the soluble cytosolic proteins from the remainder of the cellular components. The cytosolic proteins were analyzed using two-dimensional liquid chromatography and tandem mass spectrometry (MS/MS). Spectral counting along with average MS/MS total ion current were used to quantify temporal changes in relative protein abundance. In all, 461 proteins were confidently identified, of which 24 exhibited statistically significant changes in abundance. To validate these techniques, several of the observed abundance changes were confirmed by Western blotting. Data from the cytosolic fractions were then combined with previous proteomic data, and pathway analyses were performed to identify the primary pathways that are activated or inhibited in the proximal convoluted tubule during the onset of metabolic acidosis.

scholarly journals Inositol lipid signalling occurs in brush-border membranes during initiation of compensatory renal growth in the rat

1993 ◽  
Vol 295 (2) ◽  
pp. 599-605 ◽  
Author(s):  
H Banfić ◽  
M Vuica ◽  
M Knotek ◽  
S Moslavac ◽  
N Divecha
Keyword(s):  
Brush Border ◽  
Plasma Membranes ◽  
Rat Kidney ◽  
Unilateral Nephrectomy ◽  
Kidney Cortex ◽  
Compensatory Renal Growth ◽  
Rat Kidney Cortex ◽  
Contralateral Kidney ◽  
Inositol Lipids ◽  
Stimulation Of

Using highly specific mass assays, concentrations of inositol lipids and 1,2-diacylglycerol (DAG) were determined in plasma membranes isolated from rat kidney cortex. Significantly higher concentrations of inositol lipids were determined in brush-border (BBM) than in basal-lateral (BLM) plasma membranes, although DAG concentrations were similar in both. After unilateral nephrectomy, a decrease in PtdIns(4,5)P2 and PtdIns4P, with a concomitant increase in DAG and translocation of protein kinase C (PKC), were observed in BBM but not in BLM isolated from the remaining kidney. On the other hand, stimulation of renal cortical slices with insulin-like growth factor II (IGF-II) or phenylephrine caused similar effects in BLM but not in BBM. Stimulation of phospholipase C activity with translocation of PKC only to BBM in one kidney was also induced by occlusion of blood flow through the contralateral kidney for 15 min. At 30 min after the occlusion was removed and reflow established, DAG concentration and the amount of PKC in BBM returned to control values. These results suggest that an early signal after unilateral nephrectomy is transmitted to cells through BBM and can be switched on and off by blood occlusion and reflow through the contralateral kidney, while hormonal signals caused by IGF-II and phenylephrine are transmitted to cells through BLM.

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.

Stimulation of ouabain-sensitive86Rb+uptake and Na+,K+-ATPase α-subunit phosphorylation by a cAMP-dependent signalling pathway in intact cells from rat kidney cortex

FEBS Letters ◽  
1996 ◽  
Vol 396 (2-3) ◽  
pp. 309-314 ◽  
Author(s):  
Maria Luisa Carranza ◽  
Eric Féraille ◽  
Militza Kiroytcheva ◽  
Martine Rousselot ◽  
Hervé Favre
Keyword(s):  
Rat Kidney ◽  
Signalling Pathway ◽  
Kidney Cortex ◽  
Intact Cells ◽  
Α Subunit ◽  
Rat Kidney Cortex ◽  
Stimulation Of

scholarly journals Stimulation by glucose of gluconeogenesis in hepatocytes isolated from starved rats

1987 ◽  
Vol 245 (3) ◽  
pp. 661-668 ◽  
Author(s):  
M Rigoulet ◽  
X M Leverve ◽  
P J A M Plomp ◽  
A J Meijer
Keyword(s):  
Steady State ◽  
Production Rate ◽  
Pyruvate Carboxylase ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Glucose Production ◽  
Carboxylase Activity ◽  
Maximal Stimulation ◽  
Intracellular Concentrations ◽  
Effect Of Glucose ◽  
Stimulation Of

Control properties of the gluconeogenic pathway in hepatocytes isolated from starved rats were studied in the presence of glucose. The following observations were made. (1) Glucose stimulated the rate of glucose production from 20 mM-glycerol, from a mixture of 20 mM-lactate and 2 mM-pyruvate, or from pyruvate alone; no stimulation was observed with 20 mM-alanine or 20 mM-dihydroxyacetone. Maximal stimulation was obtained between 2 and 5 mM-glucose, depending on the conditions. At concentrations above 6 mM, gluconeogenesis declined again, so that at 10 mM-glucose the glucose production rate became equal to that in its absence. (2) With glycerol, stimulation of gluconeogenesis by glucose was accompanied by oxidation of cytosolic NADH and reduction of mitochondrial NAD+ and was insensitive to the transaminase inhibitor amino-oxyacetate; this indicated that glucose accelerated the rate of transport of cytosolic reducing equivalents to the mitochondria via the glycerol 1-phosphate shuttle. (3) With lactate plus pyruvate (10:1) as substrates, stimulation of gluconeogenesis by glucose was almost additive to that obtained with glucagon. From an analysis of the effect of glucose on the curves relating gluconeogenic flux and the steady-state intracellular concentrations of gluconeogenic intermediates under various conditions, in the absence and presence of glucagon, it was concluded that addition of glucose stimulated both phosphoenolpyruvate carboxykinase and pyruvate carboxylase activity.

Sign in / Sign up

Export Citation Format

Share Document