scholarly journals Unfavorable Reduction in the Ratio of Endothelin B to A Receptors in Experimental 5/6 Nephrectomy and Adenine Models of Chronic Renal Insufficiency

2020 ◽  
Vol 21 (3) ◽  
pp. 936
Author(s):  
Suvi Törmänen ◽  
Päivi Lakkisto ◽  
Arttu Eräranta ◽  
Peeter Kööbi ◽  
Ilkka Tikkanen ◽  
...  
Keyword(s):  
Renal Insufficiency ◽  
Chronic Renal Insufficiency ◽  
Rat Kidney ◽  
Kidney Cortex ◽  
Mrna Levels ◽  
Endothelin Receptor ◽  
Protein Ratio ◽  
Protein Levels ◽  
Mrna Ratio ◽  
Endothelin B

Chronic renal insufficiency (CRI) is characterized by increased endothelin 1 (ET-1) synthesis. We studied rat kidney endothelin receptor A (ETA) and receptor B (ETB) expressions after 12 and 27 weeks of 5/6 nephrectomy, and after 12 weeks of 0.3% adenine diet, representing proteinuric and interstitial inflammation models of CRI, respectively. Uric acid and calcium-phosphate metabolism were modulated after 5/6 nephrectomy, while ETA blocker and calcimimetic were given with adenine. Endothelin receptor mRNA levels were measured using RT-qPCR and protein levels using autoradiography (5/6 nephrectomy) or ELISA (adenine model). Both 12 and 27 weeks after 5/6 nephrectomy, kidney cortex ETA protein was increased by ~60% without changes in ETB protein, and the ETB:ETA ratio was reduced. However, the ETB:ETA mRNA ratio did not change. In the adenine model, kidney ETA protein was reduced by ~70%, while ETB protein was suppressed by ~95%, and the ETB:ETA ratio was reduced by ~85%, both at the protein and mRNA levels. The additional interventions did not influence the observed reductions in the ETB:ETA ratio. To conclude, unfavorable reduction in the ETB:ETA protein ratio was observed in two different models of CRI. Therefore, ETA blockade may be beneficial in a range of diseases that cause impaired kidney function.

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 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.

scholarly journals Aldosterone rapidly activates p-PKC delta and GPR30 but suppresses p-PKC epsilon protein levels in rat kidney

2019 ◽  
Vol 53 (3) ◽  
pp. 154-164 ◽  
Author(s):  
Somchit Eiam-Ong ◽  
Mookda Chaipipat ◽  
Krissanapong Manotham ◽  
Somchai Eiam-Ong
Keyword(s):  
Rat Kidney ◽  
Kidney Cortex ◽  
Protein Abundance ◽  
Protein Levels ◽  
Pkc Delta ◽  
Pkc Epsilon ◽  
Male Wistar Rats ◽  
Pkc Alpha

AbstractObjectives. Aldosterone rapidly enhances protein kinase C (PKC) alpha and beta1 proteins in the rat kidney. The G protein-coupled receptor 30 (GPR30)-mediated PKC pathway is involved in the inhibition of the potassium channel in HEK-239 cells. GPR30 mediates rapid actions of aldosterone in vitro. There are no reports available regarding the aldosterone action on other PKC isoforms and GPR30 proteins in vivo. The aim of the present study was to examine rapid actions of aldosterone on protein levels of phosphorylated PKC (p-PKC) delta, p-PKC epsilon, and GPR30 simultaneously in the rat kidney.Methods. Male Wistar rats were intraperitoneally injected with normal saline solution or aldosterone (150 µg/kg body weight). After 30 minutes, abundance and immunoreactivity of p-PKC delta, p-PKC epsilon, and GPR30 were determined by Western blot analysis and immunohisto-chemistry, respectively.Results. Aldosterone administration significantly increased the renal protein abundance of p-PKC delta by 80% (p<0.01) and decreased p-PKC epsilon protein by 50% (p<0.05). Aldosterone injection enhanced protein immunoreactivity of p-PKC delta but suppressed p-PKC epsilon protein intensity in both kidney cortex and medulla. Protein abundance of GPR30 was elevated by aldosterone treatment (p<0.05), whereas the immunoreactivity was obviously changed in the kidney cortex and inner medulla. Aldosterone translocated p-PKC delta and GPR30 proteins to the brush border membrane of proximal convoluted tubules.Conclusions. This is the first in vivo study simultaneously demonstrating that aldosterone administration rapidly elevates protein abundance of p-PKC delta and GPR30, while p-PKC epsilon protein is suppressed in rat kidney. The stimulation of p-PKC delta protein levels by aldosterone may be involved in the activation of GPR30.

Significance of changes in TNF-α and IL-10 levels in the progression of heart failure subsequent to myocardial infarction

2006 ◽  
Vol 291 (1) ◽  
pp. H106-H113 ◽  
Author(s):  
K. Kaur ◽  
A. K. Sharma ◽  
P. K. Singal
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Coronary Artery ◽  
Cardiac Function ◽  
Interleukin 10 ◽  
Mrna Levels ◽  
Protein Ratio ◽  
Protein Levels ◽  
Tnf Α ◽  
Membrane Bound

We tested whether a decrease in the ratio of interleukin-10 (IL-10) to tumor necrosis factor-α (TNF-α) correlates with the decrease in cardiac function in heart failure. It has been suggested that TNF-α plays a role in the progression of heart failure, and the effect of TNF-α in many tissues is modulated by IL-10. Any relation of these two cytokines to heart failure has never been examined. Cardiac function was assessed by echocardiographic and hemodynamic techniques in coronary artery-ligated rats at 1, 4, 8, and 16 wk after myocardial infarction (MI). Membrane-bound and soluble fractions of TNF-α and IL-10 proteins, the ratio of TNF-α to IL-10, and TNF-α and IL-10 mRNA levels were analyzed. Losartan was used to modify cardiac function in rats 4 wk after MI to further validate the relation between the IL-10-to-TNF-α ratio and cardiac function. Cardiac function deteriorated with time in all coronary artery-ligated groups, with severe failure at 16 wk after MI. Membrane-bound and soluble TNF-α protein fractions were increased 1 and 4 wk after MI, whereas TNF -α mRNA was increased 4 and 8 wk after MI. Membrane-bound IL-10 protein and mRNA levels were decreased 4, 8, and 16 wk after MI. The decrease in the IL-10-to-TNF-α protein ratio in all coronary artery-ligated groups correlated with the depressed cardiac function. Losartan improved cardiac function, membrane-bound and soluble TNF-α and IL-10 protein levels, the ratio of IL-10 to TNF-α, and IL-10 mRNA. This study suggests that a decrease in IL-10 and IL-10-to-TNF-α ratio correlates with depressed cardiac function.

Parathyroid gland calcium receptor mRNA levels are unaffected by chronic renal insufficiency or low dietary calcium in rats

Endocrine ◽  
1995 ◽  
Vol 3 (11) ◽  
pp. 769-774 ◽  
Author(s):  
Kimberly V. Rogers ◽  
Rebecca L. Conklin ◽  
Stacey H. Lowe ◽  
Barbara A. Petty
Keyword(s):  
Renal Insufficiency ◽  
Parathyroid Gland ◽  
Chronic Renal Insufficiency ◽  
Dietary Calcium ◽  
Mrna Levels ◽  
Calcium Receptor ◽  
Receptor Mrna

Impairment of Phenylalanine Hydroxylation in Chronic Renal Insufficiency

1973 ◽  
Vol 45 (1) ◽  
pp. 89-97 ◽  
Author(s):  
G. A. Young ◽  
F. M. Parsons
Keyword(s):  
Renal Insufficiency ◽  
Chronic Renal Insufficiency ◽  
Phenylalanine Hydroxylase ◽  
Rat Kidney ◽  
Kidney Tissue ◽  
Amino Nitrogen ◽  
Normal Subjects ◽  
The Individual ◽  
Plasma Tyrosine ◽  
Low Activity

1. Plasma tyrosine and phenylalanine were measured in patients with chronic renal failure and in normal subjects. Plasma tyrosine to phenylalanine ratio was greatly decreased in patients with creatinine clearance less than 16 ml/min, suggesting an impairment of phenylalanine hydroxylation. This ratio correlated with the percentage of essential to total amino nitrogen in the plasma. 2. Phenylalanine hydroxylase from rat liver was inhibited or inactivated (15%) by uraemic plasma but this could not be attributed to the individual effects of urea, creatinine, uric acid, oxalic acid, phenylpyruvic acid, glycine or phosphate. It is unlikely that the degree of inhibition was sufficient to account for the impairment of phenylalanine hydroxylation in chronic renal insufficiency. 3. Phenylalanine hydroxylase was present in rat kidney but at a very low activity relative to that present in liver; consequently, the loss of functional kidney tissue associated with chronic renal insufficiency is unlikely to impair phenylalanine hydroxylation. 4. Plasma tyrosine and liver phenylalanine hydroxylase activity were significantly decreased in partially nephrectomized rats when protein intake was inadequate.

scholarly journals Gene-Specific Predictability of Protein Levels from mRNA Data in Humans

2018 ◽  
Author(s):  
Alief Moulana ◽  
Adriana Scanteianu ◽  
DeAnalisa Jones ◽  
Alan D. Stern ◽  
Mehdi Bouhaddou ◽  
...  
Keyword(s):  
Predictive Power ◽  
Protein Abundance ◽  
Mrna Levels ◽  
Protein Expression Profile ◽  
Protein Ratio ◽  
Transcriptomic Data ◽  
Protein Levels ◽  
Profile Changes ◽  
Specific Tissue ◽  
Transmembrane Transporter

AbstractTranscriptomic data are widely available, and the extent to which they are predictive of protein abundances remains debated. Using multiple public databases, we calculate mRNA and mRNA-to-protein ratio variability across human tissues to quantify and classify genes for protein abundance predictability confidence. We propose that such predictability is best understood as a spectrum. A gene-specific, tissue-independent mRNA-to-protein ratio plus mRNA levels explains ∼80% of protein abundance variance for more predictable genes, as compared to ∼55% for less predictable genes. Protein abundance predictability is consistent with independent mRNA and protein data from two disparate cell lines, and mRNA-to-protein ratios estimated from publicly-available databases have predictive power in these independent datasets. Genes with higher predictability are enriched for metabolic function, tissue development/cell differentiation roles, and transmembrane transporter activity. Genes with lower predictability are associated with cell adhesion, motility and organization, the immune system, and the cytoskeleton. Surprisingly, many genes that regulate mRNA-to-protein ratios are constitutively expressed but also exhibit ratio variability, suggesting a general autoregulation mechanism whereby protein expression profile changes can be implemented quickly, or homeostatic sensing stabilizes protein abundances under fluctuating conditions. Gene classifications and their mRNA-to-protein ratios are provided as a resource to facilitate protein abundance predictions by others.

Abstract 121: Hyperglycemia-induced Prorenin Receptor Abundance on Plasma Membrane of Kidney Collecting Duct Cells: is a Novel Mechanism to Explain Diabetic Nephropathy?

2015 ◽  
Vol 117 (suppl_1) ◽  
Author(s):  
Venkateswara R Gogulamudi ◽  
Danielle Y Arita ◽  
Camille RT Bourgeois ◽  
Ryosuke Satou ◽  
Minolfa C Prieto
Keyword(s):  
Diabetic Nephropathy ◽  
Plasma Membrane ◽  
Collecting Duct ◽  
Rat Kidney ◽  
Mrna Levels ◽  
Protein Levels ◽  
Duct Cells ◽  
Prorenin Receptor ◽  
Membrane Bound ◽  
Collecting Duct Cells

Activation of the renin-angiotensin system (RAS) leads to nephropathy during Diabetes Mellitus (DM). Prorenin levels are increased in the circulation of DM patients and predict microvascular damage. In streptozotocin (STZ)-induced type 1 DM rats, the collecting duct is the major source of prorenin in the kidney. The prorenin receptor (PRR), a new RAS component, elicits intracellular signals linked to fibrosis upon binding of prorenin at the cell plasma membrane (PM). We propose that PRR may contribute to the development of tubulointerstitial fibrosis by being locally activated by prorenin. To support this concept, we tested the hypothesis that hyperglycemia increases membrane bound PRR to collecting duct cells. To address this hypothesis, we used T1DM rats (N=10) induced with a single STZ injection (ip; 200ng/kg x 7 d) as well as mouse collecting duct M-1 cells, treated at different time intervals 0, 5 min, 1, 12, and 24 h with normal glucose (NG; 5mM glucose+20mM mannitol) and high glucose (HG; 25mM) to assess PRR trafficking alterations induced by glucose. After 7-days induction, STZ-rats showed plasma glucose as 428±13 vs.138±9 gr/dl and plasma insulin as 0.07±0.02 vs 2.42 ng/ml; compared to controls. By immunofluorescence (IF) in rat kidney sections, PRR was mainly localized on the apical aspect of collecting duct cells in STZ-rats, while in controls most of PRR signal was observed intracellularly. Although PRR mRNA levels did not differ in the collecting ducts between groups; its protein levels were augmented in STZ-rats. Importantly, compared with NG-treated cells, PRR protein levels (membrane bound) were significantly higher in PM extracts from M-1 cells treated with HG, and a maximum peak was observed at 1 h. Interestingly, in de-convoluted IF images of M-1 cells, PRR was localized mainly in the perinuclear areas during NG conditions; however, in HG-treated cells, PRR was found toward the cell surface. These data suggest that hyperglycemia induces PRR trafficking alterations of PRR. The present results suggest that hyperglycemia-induced PRR abundance on the PM in the collecting duct might be a novel mechanism underlying the development of diabetic nephropathy, particularly tissue fibrosis in DM. Grant support by the NIH-NIDDK (DK104375-01)

scholarly journals p52(PAI-1) and actin expression in butyrate-induced flat revertants of v-ras-transformed rat kidney cells

1991 ◽  
Vol 279 (3) ◽  
pp. 883-890 ◽  
Author(s):  
P J Higgins ◽  
M P Ryan
Keyword(s):  
Rat Kidney ◽  
Plasminogen Activator Inhibitor ◽  
Cytoskeletal Proteins ◽  
Kidney Cells ◽  
Mrna Levels ◽  
Focal Contact ◽  
Protein Levels ◽  
Associated Proteins ◽  
Activator Inhibitor Type ◽  
Pai 1

Flat revertants of v-ras-transformed (KNRK) rat kidney cells, which express elevated levels of p21ras protein, were generated to high efficiencies with sodium butyrate (NaB). Overall protein synthesis in revertants was not different from parental cells, although changes were evident in expression and distribution of specific microfilament-associated cytoskeletal proteins. Quantitative two-dimensional electrophoresis revealed revertant-associated 3-4-fold increases in cytoskeletal deposition of the microfilament-associated proteins gelsolin and vinculin correlating with microfilament reorganization and focal-contact formation respectively. Similar increases in actin content were evident at both the total-cellular- and cytoskeletal-associated-protein levels. In contrast, intermediate-filament family elements (vimentin, lamins) remained unaltered. The only unique protein resolved in flat revertants was p52, a 52 kDa extracellular-matrix-associated protein previously identified as plasminogen-activator inhibitor type 1 (PAI-1). p52(PAI-1) expression was induced early during generation of the revertant phenotype and preceded development of focal-contact structures. NaB-induced p52(PAI-1) synthesis and generation of early morphological reversion in KNRK cells required ongoing RNA synthesis, since exposure to actinomycin D before addition of NaB inhibited both events. p52(PAI-1) induction by NaB was regulated at the level of mRNA abundance; in contrast, actin mRNA levels were the same in parental and revertant cells, suggesting that the increased actin content which typified the revertant phenotype was due to augmented actin microfilament stability.

scholarly journals Parallel regulation of procollagen I and colligin, a collagen-binding protein and a member of the serine protease inhibitor family.

1993 ◽  
Vol 121 (1) ◽  
pp. 193-199 ◽  
Author(s):  
E P Clarke ◽  
N Jain ◽  
A Brickenden ◽  
I A Lorimer ◽  
B D Sanwal
Keyword(s):  
Cell Lines ◽  
Binding Protein ◽  
Rat Kidney ◽  
Mrna Levels ◽  
Experimental Conditions ◽  
Collagen Binding ◽  
Protein Levels ◽  
Short Period ◽  
Normal Rat ◽  
Steady State Levels

A potential regulatory linkage between the biosynthesis of colligin, a collagen-binding protein of the ER, and procollagen I was examined under a variety of experimental conditions. Cell lines which did not produce a significant amount of procollagen I mRNA also lacked the capacity to produce colligin mRNA. Anchorage-dependent cell lines like L6 myoblasts and normal rat kidney fibroblasts produced both colligin and procollagen I mRNA, but the level of both was concurrently reduced considerably in their ras-transformed counterparts. Similarly, during the differentiation of L6 myoblasts, levels of both colligin and procollagen declined together. Treatment of myoblasts by dexamethasone or EGF led to a decrease in the steady-state levels of procollagen I mRNA, and this was, again, accompanied by a decrease in colligin mRNA synthesis. On the other hand, when the rate of procollagen I synthesis was stimulated by treatment of myoblasts with TGF beta, it led to the concurrent augmentation of both the mRNA and protein levels of colligin. A linkage between the regulation of synthesis of procollagen I and colligin thus seems to exist. The only exception to this generalization is provided by the heat induction behavior of the two proteins. Treatment of myoblasts for a very short period leads to an increase in the synthesis of both the mRNA and protein levels of colligin. This, however, is not accompanied by a change in the mRNA levels of procollagen I. These studies establish that colligin and procollagen are generally tightly co-regulated except after heat shock, suggesting an important functional linkage.

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