Primary response gene expression in renal hypertrophy and hyperplasia: evidence for different growth initiation processes

1991 ◽  
Vol 260 (6) ◽  
pp. F823-F827 ◽  
Author(s):  
D. A. Kujubu ◽  
J. T. Norman ◽  
H. R. Herschman ◽  
L. G. Fine
Keyword(s):  
Folic Acid ◽  
Cellular Response ◽  
Primary Response ◽  
Unilateral Nephrectomy ◽  
Transcriptional Level ◽  
Sham Operation ◽  
Mrna Levels ◽  
Renal Hypertrophy ◽  
Hypertrophic Response ◽  
Contralateral Kidney

Unilateral nephrectomy is followed by compensatory renal hypertrophy, a response in which the cells of the contralateral kidney increase in size and protein content without synthesizing DNA or dividing. To determine whether the earliest phase of the hypertrophic response has features similar to mitogenic or differentiation responses, we have characterized the expression of several primary-response genes, the 12-O-tetradecanoylphorbol-13-acetate (TPA)-inducible sequences (TIS) genes, which are rapidly and transiently induced in the absence of intervening protein synthesis, in a variety of mitogenic and differentiation cell systems. TIS gene induction was studied in the contralateral kidney of uninephrectomized and sham-operated mice, as well as in the kidneys of mice in which renal cell proliferation was induced by folic acid injection. Induction of TIS 1, TIS 8, and TIS 11 mRNA levels following folic acid administration peaked at 2 to 4 h and persisted up to 6 to 12 h after mitogenic stimulation. In contrast, a qualitatively different pattern was observed after both uninephrectomy and sham operation; a short-lived increase (up to 1 h) in mRNA levels occurred for the three TIS genes. This pattern was qualitatively similar to that observed in the sham-operated animals. We conclude that renal hypertrophy induced by unilateral nephrectomy is a distinct cellular response, distinguishable at the earliest transcriptional level from a mitogenic response and from the responses that characterize several pathways of cell differentiation.

Early increase in pulsatile growth hormone release after unilateral nephrectomy in adult rats

1994 ◽  
Vol 266 (4) ◽  
pp. F628-F632 ◽  
Author(s):  
A. Haramati ◽  
M. D. Lumpkin ◽  
S. E. Mulroney
Keyword(s):  
Growth Hormone ◽  
Early Time ◽  
Peak Level ◽  
Unilateral Nephrectomy ◽  
Sham Operation ◽  
Renal Growth ◽  
Adult Rats ◽  
Compensatory Renal Growth ◽  
Jugular Veins ◽  
Hypertrophic Response

Removal of one kidney results, within days, in accelerated growth of the remaining kidney. However, the mechanisms that underlie this compensatory renal hypertrophic response, particularly in the early time period following nephrectomy, are not understood. In this study we tested the hypothesis that removal of one kidney leads to a change in the pulsatile release of growth hormone (GH), which facilitates compensatory renal growth. Adult Wistar rats were implanted with Silastic cannulas in jugular veins and underwent either unilateral nephrectomy (UNX) or sham operation. Plasma levels of GH were determined 24 and 48 h after sham operation or UNX. Blood samples were taken every 20 min over a 6-h period from conscious, unrestrained animals. Pulsatile GH release was markedly elevated 24 h after UNX in both the amplitude of the surges as well as in the duration of release. Peak GH levels after 24 h were three- to fourfold higher in UNX rats compared with sham controls (417 +/- 75 vs. 119 +/- 23 ng/ml, P < 0.05). However, this enhanced release of GH appeared to be of short duration and began declining by 48 h post-UNX (peak level of 227 +/- 37 ng/ml, P < 0.05 vs. both 24 h UNX and sham controls). To examine whether this rise in GH release post-UNX contributed to the compensatory renal growth, rats underwent UNX and were immediately treated with an antagonist to GH-releasing factor (GRF-AN; i.e., [N-Ac-Tyr1,D-Arg2]GRF-(1-29) amide, 200 micrograms/kg twice daily), and the effects on GH release and renal growth were determined. Administration of GRF-AN significantly suppressed the increase in GH release post-UNX and was associated with a significant attenuation in renal growth 48 h post-UNX in GRF-AN-treated rats (8.7 +/- 2.6% vs. 22.7 +/- 3.0% in UNX controls, P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Syk Plays a Critical Role in the Expression and Activation of IRAK1 in LPS-Treated Macrophages

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Jae Gwang Park ◽  
Young-Jin Son ◽  
Byong Chul Yoo ◽  
Woo Seok Yang ◽  
Ji Hye Kim ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Protein Tyrosine Kinase ◽  
Interleukin 1 ◽  
Mrna Level ◽  
Critical Role ◽  
Primary Response ◽  
Transcriptional Level ◽  
Mrna Levels ◽  
Treatment Conditions ◽  
Lps Treatment

To address how interleukin-1 receptor-associated kinase 1 (IRAK1) is controlled by other enzymes activated by toll-like receptor (TLR) 4, we investigated the possibility that spleen tyrosine kinase (Syk), a protein tyrosine kinase that is activated at an earlier stage during TLR4 activation, plays a central role in regulating the functional activation of IRAK1. Indeed, we found that overexpression of myeloid differentiation primary response gene 88 (MyD88), an adaptor molecule that drives TLR signaling, induced IRAK1 expression and that piceatannol, a Syk inhibitor, successfully suppressed the MyD88-dependent upregulation of IRAK1 under LPS treatment conditions. Interestingly, in Syk-knockout RAW264.7 cells, IRAK1 activity was almost completely blocked after LPS treatment, while providing a Syk-recovery gene to the knockout cells successfully restored IRAK1 expression. According to our measurements of IRAK1 mRNA levels, the transcriptional upregulation of IRAK1 was induced by LPS treatment between 4 and 60 min, and this can be suppressed in Syk knockout cells, providing an effect similar that that seen under piceatannol treatment. The overexpression of Syk reverses this effect and leads to a significantly higher IRAK1 mRNA level. Collectively, our results strongly suggest that Syk plays a critical role in regulating both the activity and transcriptional level of IRAK1.

scholarly journals Primary and secondary genetic responses after folic acid-induced acute renal injury in the mouse.

1994 ◽  
Vol 5 (6) ◽  
pp. 1324-1332
Author(s):  
J P Calvet ◽  
L J Chadwick
Keyword(s):  
Protein Synthesis ◽  
Folic Acid ◽  
Ornithine Decarboxylase ◽  
Renal Injury ◽  
Primary Response ◽  
Protein Synthesis Inhibitor ◽  
Mrna Levels ◽  
Acute Renal Injury ◽  
Primary Response Genes ◽  
Initial Injury

Folic acid-induced acute renal injury results in dramatic changes in gene expression. Among the genes affected by folic acid treatment are the primary response genes, c-fos and c-myc, which are thought to function to initiate cell cycle events. In this report, changes in the expression of three other genes in response to folic acid injury have been investigated: ornithine decarboxylase, epidermal growth factor (EGF), and sulfated glycoprotein-2 (SGP-2). Renal injury was found to cause a rapid decrease in EGF mRNA, which remained absent for several days after the initial injury, gradually returning to normal levels over an approximately 3-wk regeneration and recovery period. Ornithine decarboxylase mRNA showed a similar decrease. In contrast, folic acid caused a rapid increase in SGP-2 mRNA, which peaked several days after treatment, decreasing to normal levels over the 3-wk period. The mRNAs for the primary response genes were superinduced in the injured kidneys in the presence of the protein synthesis inhibitor cycloheximide. In contrast, the changes in EGF and SGP-2 mRNA levels were blocked by cycloheximide, indicating that these responses required new protein synthesis during the first few hours after folic acid injury. The opposite but parallel responses in the expression of the EGF and SGP-2 genes suggest that their regulation is coupled to the initial injury-induced dedifferentiation and subsequent return to the fully differentiated state.

Abstract P117: Does Mammalian Target of Rapamycin Complex-2 Regulate Protein Degradation Pathways in the Heart?

2011 ◽  
Vol 109 (suppl_1) ◽  
Author(s):  
Pankaj S Shende ◽  
Christian Morandi ◽  
Marijke Brink
Keyword(s):  
Gene Expression ◽  
Protein Degradation ◽  
Mammalian Target Of Rapamycin ◽  
Proteasomal Degradation ◽  
Degradation Pathway ◽  
Target Of Rapamycin ◽  
Transcriptional Level ◽  
Mrna Levels ◽  
Hypertrophic Response ◽  
Akt Phosphorylation

Background: Mammalian target of rapamycin (mTOR) occurs in the cell in two distinct multiprotein complexes called mTOR complex 1 (mTORC1) and mTORC2, which contain raptor and rictor, respectively. We have recently demonstrated that mTORC1 activity is required for the hypertrophic response to aortic constriction and for the normal cardiac homeostasis. Moreover, we showed that raptor deletion causes Akt hyperphosphorylation and lower gene expression of Atrogin-1 and MuRF1, two muscle specific E3 enzymes part of the proteasomal degradation pathway. These results suggested that, as a counter-regulatory response to mTORC1 inactivation, mTORC2 reduces protein degradation via phosphorylation of Akt at Ser473. It has previously been shown that the phosphorylation state of Akt regulates Atrogin-1 and MuRF1 gene expression at the transcriptional level via FoxO. In the present study, we have tested whether mTORC2 inactivation induces the ubiquitin-proteasomal degradation pathway. Methods and results: In 10 week-old male mice, transgenic for MerCreMer driven by the α-MHC promoter and homozygous for floxed rictor, deletion of the rictor gene was induced by tamoxifen. Protein and RNA extracts were analyzed at three weeks after tamoxifen by Western blotting and qPCR, respectively. The rictor gene was efficiently ablated from the heart as its protein levels were reduced. Phosphorylation of Akt and PKC-α, direct targets of mTORC2, was abolished, identifying these signaling molecules as downstream targets of mTORC2 in the heart. However, the reduced Akt phosphorylation was not associated with any changes in the mRNA levels of Atrogin-1, MuRF1, and MuRF3. Conclusion: Our study suggests that mTORC2-induced phosphorylation of Akt is not required for the maintenance of low expression levels of these genes. Further studies are ongoing to identify the factors that modulate Atrogin-1 and MuRF1 gene transcription in the heart.

scholarly journals Concentration of phosphoribosyl pyrophosphate in renal hypertrophy. Contrasting effects of early diabetes and unilateral nephrectomy

1986 ◽  
Vol 239 (1) ◽  
pp. 241-244 ◽  
Author(s):  
S Kunjara ◽  
M Sochor ◽  
A L Greenbaum ◽  
P McLean
Keyword(s):  
Nucleic Acid ◽  
Unilateral Nephrectomy ◽  
Phosphoribosyl Pyrophosphate ◽  
Renal Hypertrophy ◽  
Early Diabetes ◽  
Nucleotide Synthesis ◽  
Contralateral Kidney ◽  
Increment Of Growth ◽  
Renal Enlargement

Studies were made of the renal phosphoribosyl pyrophosphate (PPRibP) content and PPRibP synthetase (EC 2.7.6.1) activity in rats diabetic for 5, 14 or 20 days, or unilaterally nephrectomized (UN) for 5 days, and in doubly lesioned animals. Approximately equal degrees of renal enlargement were found after 5 days diabetes or 5 days UN. In the doubly lesioned animals the increment of growth was additive. Unilateral nephrectomy of 5 days duration, in contrast with diabetes, had no effect on the PPRibP content of the contralateral kidney, nor did it modify the renal PPRibP content when performed on animals diabetic for 5, 14 or 20 days. The activity of PPRibP synthetase was unaffected by diabetes, UN or diabetes +UN. The results pinpoint a stage of nucleotide synthesis which is differentially affected by the two stimuli, in line with evidence for differences in regulation of nucleic acid turnover in the two conditions.

scholarly journals THE PATHOGENESIS OF HYPERTENSION INDUCED BY RENAL CONSTRICTION

1950 ◽  
Vol 92 (1) ◽  
pp. 59-76 ◽  
Author(s):  
L. J. Rather
Keyword(s):  
Blood Pressure ◽  
Young Male ◽  
The Other ◽  
Unilateral Nephrectomy ◽  
Albino Rats ◽  
Renal Hypertrophy ◽  
Ether Anesthesia ◽  
Frequency Distributions ◽  
Contralateral Kidney ◽  
Blood Pressures

Blood pressures were determined on forty-two young male albino rats and a basal level established. The rats were then divided into four groups and subjected to one of the following operations: (a) unilateral nephrectomy with exposure and handling of the opposite kidney; (b) unilateral nephrectomy and constriction of the remaining kidney with a silk figure-of-eight ligature; (c) unilateral renal constriction with a silk figure-of-eight ligature, the other kidney being left intact after exposure and handling; (d) unilateral nephrectomy and removal of the poles of the contralateral kidney (three-quarters nephrectomy). The animals were followed for 50 days, during which blood pressures were measured on twenty occasions, then killed by exsanguination under ether anesthesia. The organs were weighed according to a standardized procedure and studied histologically. Individual determinations of serum creatinine and of the hematocrit levels were made. Mean lines and frequency distributions of blood pressure were subjected to statistical analysis. A definitely significant increase in blood pressure developed in the group subjected to operation (b) within 4 days postoperative. In none of the other groups did hypertension develop. Analysis of the individual renal weights and creatinine levels indicates the independence of the development of hypertension from the total mass of functioning renal tissue. Nor is it dependent on the prevention of renal hypertrophy or the presence of fibrous perinephritis. The effect is probably due to the production of a disturbance of hemodynamics or tissue tension with the liberation of a pressor substance by the injured kidney.

The Morphology of the Rat Kidney Following Folic Acid Administration

1970 ◽  
Vol 28 ◽  
pp. 200-201
Author(s):  
Aline Byrnes ◽  
Elsa E. Ramos ◽  
Minoru Suzuki ◽  
E.D. Mayfield
Keyword(s):  
Folic Acid ◽  
De Novo ◽  
Specific Activity ◽  
Rat Kidney ◽  
Present Report ◽  
Intracellular Localization ◽  
Male Rats ◽  
Renal Hypertrophy ◽  
Electron Microscopic ◽  
Biochemical Alterations

Renal hypertrophy was induced in 100 g male rats by the injection of 250 mg folic acid (FA) dissolved in 0.3 M NaHCO3/kg body weight (i.v.). Preliminary studies of the biochemical alterations in ribonucleic acid (RNA) metabolism of the renal tissue have been reported recently (1). They are: RNA content and concentration, orotic acid-c14 incorporation into RNA and acid soluble nucleotide pool, intracellular localization of the newly synthesized RNA, and the specific activity of enzymes of the de novo pyrimidine biosynthesis pathway. The present report describes the light and electron microscopic observations in these animals. For light microscopy, kidney slices were fixed in formalin, embedded, sectioned, and stained with H & E and PAS.

Endotoxin-Induced Tissue Factor in Human Monocytes is Dependent upon Protein Kinase C Activation

1993 ◽  
Vol 70 (05) ◽  
pp. 800-806 ◽  
Author(s):  
C Ternisien ◽  
M Ramani ◽  
V Ollivier ◽  
F Khechai ◽  
T Vu ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Tissue Factor ◽  
Factor Ix ◽  
Transcriptional Level ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Human Monocytes ◽  
Kinase C ◽  
Pkc Activation

SummaryTissue factor (TF) is a transmembrane receptor which, in association with factors VII and Vila, activates factor IX and X, thereby activating the coagulation protease cascades. In response to bacterial lipopolysaccharide (LPS) monocytes transcribe, synthesize and express TF on their surface. We investigated whether LPS-induced TF in human monocytes is mediated by protein kinase C (PKC) activation. The PKC agonists phorbol 12- myristate 13-acetate (PMA) and phorbol 12, 13 dibutyrate (PdBu) were both potent inducers of TF in human monocytes, whereas 4 alpha-12, 13 didecanoate (4 a-Pdd) had no such effect. Both LPS- and PMA-induced TF activity were inhibited, in a concentration dependent manner, by three different PKC inhibitors: H7, staurosporine and calphostin C. TF antigen determination confirmed that LPS-induced cell-surface TF protein levels decreased in parallel to TF functional activity under staurosporine treatment. Moreover, Northern blot analysis of total RNA from LPS- or PMA-stimulated monocytes showed a concentration-dependent decrease in TF mRNA levels in response to H7 and staurosporine. The decay rate of LPS-induced TF mRNA evaluated after the arrest of transcription by actinomycin D was not affected by the addition of staurosporine, suggesting that its inhibitory effect occurred at a transcriptional level. We conclude that LPS-induced production of TF and its mRNA by human monocytes are dependent on PKC activation.

scholarly journals Methylobacterium oryzae Influences Isoepoxydon Dehydrogenase Gene Expression and Patulin Production by Penicillium expansum

Water ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 1427
Author(s):  
Tiago Barros Afonso ◽  
Lúcia Chaves Simões ◽  
Nelson Lima
Keyword(s):  
Gene Expression ◽  
Distribution Systems ◽  
Water Distribution ◽  
Penicillium Expansum ◽  
Transcriptional Level ◽  
Positive Trend ◽  
Mrna Levels ◽  
Expression Levels ◽  
Production Values ◽  
Methylobacterium Oryzae

Biofilms can be considered the main source of microorganisms in drinking water distribution systems (DWDS). The ecology of a biofilm is dependent on a variety of factors, including the presence of microbial metabolites excreted by its inhabitants. This study reports the effect of the Gram-negative bacteria Methylobacterium oryzae on the idh gene expression levels and patulin production of Penicillium expansum mature biofilms. For this purpose, a RT-qPCR method to quantify idh mRNA levels was applied. In addition, the idh expression levels were compared with the patulin production. The results obtained revealed that the effect of the bacterium on pre-established P. expansum biofilms is dependent on the time of interaction. More mature P. expansum biofilms appear to be more resistant to the inhibitory effect that M. oryzae causes towards idh gene expression and patulin production. A positive trend was observed between the idh expression and patulin production values. The results indicate that M. oryzae affects patulin production by acting at the transcriptional level of the idh gene.

Cyclic AMP analogs and retinoic acid influence the expression of retinoic acid receptor alpha, beta, and gamma mRNAs in F9 teratocarcinoma cells

1990 ◽  
Vol 10 (1) ◽  
pp. 391-396
Author(s):  
L Hu ◽  
L J Gudas
Keyword(s):  
Retinoic Acid ◽  
Steady State ◽  
Cyclic Amp ◽  
Cellular Response ◽  
Retinoic Acid Receptor ◽  
Mrna Level ◽  
Mrna Levels ◽  
Protein Synthesis Inhibitors ◽  
Receptor Alpha ◽  
F9 Teratocarcinoma

Retinoic acid (RA) receptor alpha (RAR alpha) and RAR gamma steady-state mRNA levels remained relatively constant over time after the addition of RA to F9 teratocarcinoma stem cells. In contrast, the steady-state RAR beta mRNA level started to increase within 12 h after the addition of RA and reached a 20-fold-higher level by 48 h. This RA-associated RAR beta mRNA increase was not prevented by protein synthesis inhibitors but was prevented by the addition of cyclic AMP analogs. In the presence of RA, cyclic AMP analogs also greatly reduced the RAR alpha and RAR gamma mRNA levels, even though cyclic AMP analogs alone did not alter these mRNA levels. The addition of either RA or RA plus cyclic AMP analogs did not result in changes in the three RAR mRNA half-lives. These results suggest that agents which elevate the internal cyclic AMP concentration may also affect the cellular response to RA by altering the expression of the RARs.

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