Regulation of urea synthesis during the acute-phase response in rats

2013 ◽  
Vol 304 (7) ◽  
pp. G680-G686 ◽  
Author(s):  
Karen Louise Thomsen ◽  
Niels Jessen ◽  
Andreas Buch Møller ◽  
Niels Kristian Aagaard ◽  
Henning Grønbæk ◽  
...  
Keyword(s):  
Acute Phase ◽  
Acute Phase Response ◽  
Urea Cycle ◽  
Acute Phase Proteins ◽  
Phase Response ◽  
Mrna Levels ◽  
Urea Synthesis ◽  
Cycle Enzyme ◽  
Tnf Α ◽  
Urea Cycle Enzyme

The acute-phase response is a catabolic event involving increased waste of amino-nitrogen (N) via hepatic urea synthesis, despite an increased need for amino-N incorporation into acute-phase proteins. This study aimed to clarify the regulation of N elimination via urea during different phases of the tumor necrosis factor-α (TNF-α)-induced acute-phase response in rats. We used four methods to study the regulation of urea synthesis: We examined urea cycle enzyme mRNA levels in liver tissue, the hepatocyte urea cycle enzyme proteins, the in vivo capacity of urea-N synthesis (CUNS), and known humoral regulators of CUNS at 1, 3, 24, and 72 h after TNF-α injection (25 μg/kg iv rrTNF-α) in rats. Serum acute-phase proteins and their liver mRNA levels were also measured. The urea cycle enzyme mRNA levels acutely decreased and then gradually normalized, whereas the urea cycle enzyme proteins remained essentially unchanged over time. The CUNS rose after 3 h and then normalized. The acute-phase response was fully activated at 24 h with markedly increased serum levels of the acute-phase proteins. TNF-α acutely upregulated the CUNS. Later, despite the fully established 24-h acute-phase response and the decreased activity of the urea cycle enzyme genes, there was no change in the urea cycle enzyme proteins or the CUNS. Thus in no phase after the initiation of the acute-phase response was in vivo urea synthesis orchestrated in combination with acute-phase protein synthesis so as to limit N waste.

Immune Alterations, Lipid Peroxidation, and Muscle Damage Following a Hill Race

2005 ◽  
Vol 30 (2) ◽  
pp. 196-211 ◽  
Author(s):  
Richard J. Simpson ◽  
Martin R. Wilson ◽  
James R. Black ◽  
James A. Ross ◽  
Greg P. Whyte ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Lipid Peroxidation ◽  
Muscle Damage ◽  
Acute Phase ◽  
Acute Phase Response ◽  
Acute Phase Proteins ◽  
Venous Blood ◽  
Total Antioxidant Status ◽  
Phase Response ◽  
Tnf Α

Hill races usually include large downhill running sections, which can induce significant degrees of muscle damage in a field setting. This study examined the link between muscle damage, oxidative stress, and immune perturbations following a 7-km mountainous hill race with 457 m of ascent and 457 m of descent. Venous blood samples were taken from 7 club level runners before, immediately after, and 48 hrs postrace. Samples were analysed for total and differential leukocyte counts, markers of muscle damage (CK), lipid peroxidation (MDA), and acute phase proteins (CRP; fibrinogen; α-1-ACT). The total antioxidant status (TEAC) and plasma levels of the proinflammatory cytokines IL-6, IL-8, and TNF-α were also determined. Subjective pain reports, and plasma activities of CK, MDA, and circulatory monocytes reached peak values at 48 hrs postrace (p <  0.05). TEAC and the cytokine IL-8 increased immediately after the race (p <  0.05). Plasma TNF-α remained unchanged (p > 0.05). Despite the reports of muscle damage and soreness, no evidence of an acute phase response was observed (p > 0.05), which may be explained by the failure of the race to induce a plasma TNF-α response. Future studies should examine the link between muscle damage, oxidative stress, and the acute phase response following hill races of longer duration with larger eccentric components. Key words: acute phase response, cytokines, antioxidant capacity, creatine kinase, field study

The acute phase response and C-reactive protein

2020 ◽  
pp. 2199-2207
Author(s):  
Mark B. Pepys
Keyword(s):  
Acute Phase ◽  
Acute Phase Response ◽  
Serum Amyloid A ◽  
Acute Phase Proteins ◽  
Phase Response ◽  
Serum Amyloid ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Amyloid A ◽  
Serum Amyloid A Protein

The acute phase response—trauma, tissue necrosis, infection, inflammation, and malignant neoplasia induce a complex series of nonspecific systemic, physiological, and metabolic responses including fever, leucocytosis, catabolism of muscle proteins, greatly increased de novo synthesis and secretion of a number of ‘acute phase’ plasma proteins, and decreased synthesis of albumin, transthyretin, and high- and low-density lipoproteins. The altered plasma protein concentration profile is called the acute phase response. Acute phase proteins—these are mostly synthesized by hepatocytes, in which transcription is controlled by cytokines including interleukin 1, interleukin 6, and tumour necrosis factor. The circulating concentrations of complement proteins and clotting factors increase by up to 50 to 100%; some of the proteinase inhibitors and α‎1-acid glycoprotein can increase three- to fivefold; but C-reactive protein (CRP) and serum amyloid A protein (an apolipoprotein of high-density lipoprotein particles) are unique in that their concentrations can change by more than 1000-fold. C-reactive protein—this consists of five identical, nonglycosylated, noncovalently associated polypeptide subunits. It binds to autologous and extrinsic materials which contain phosphocholine, including bacteria and their products. Ligand-bound CRP activates the classical complement pathway and triggers the inflammatory and opsonizing activities of the complement system, thereby contributing to innate host resistance to pneumococci and probably to recognition and safe ‘scavenging’ of cellular debris. Clinical features—(1) determination of CRP in serum or plasma is the most useful marker of the acute phase response in most inflammatory and tissue damaging conditions. (2) Acute phase proteins may be harmful in some circumstances. Sustained increased production of serum amyloid A protein can lead to the deposition of AA-type, reactive systemic amyloid.

Gene expression in regenerating and acute-phase rat liver

1990 ◽  
Vol 259 (3) ◽  
pp. G340-G347 ◽  
Author(s):  
J. Milland ◽  
A. Tsykin ◽  
T. Thomas ◽  
A. R. Aldred ◽  
T. Cole ◽  
...  
Keyword(s):  
Vitamin D ◽  
Rat Liver ◽  
Acute Phase ◽  
Acute Phase Response ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Binding Protein ◽  
Ornithine Transcarbamylase ◽  
Phase Response ◽  
Mrna Levels ◽  
Vitamin D Binding Protein

The integration of growth and the acute-phase response is investigated by comparing the mRNA levels in rat liver during acute inflammation with those after partial hepatectomy. Northern analysis is carried out for the mRNAs for thiostatin, alpha 2-macroglobulin, alpha 1-antitrypsin, inter-alpha-trypsin inhibitor subunit 1, haptoglobin, ceruloplasmin, transferrin, vitamin D-binding protein, alpha 1-acid glycoprotein, beta-fibrinogen, apolipoproteins A-IV and E, albumin, transthyretin, alpha 2-HS-glycoprotein, retinol-binding protein, beta-tubulin, c-myc protooncogene, glyceraldehyde-3-phosphate dehydrogenase, phosphoenolpyruvate carboxykinase, ornithine transcarbamylase, and alcohol dehydrogenase. The acute-phase response dominates during the first 18 h. Changes in mRNA levels related to growth of the liver become important thereafter, and the capacity for an acute-phase response of plasma protein synthesis becomes greatly reduced. The early increase in the level of ceruloplasmin mRNA observed during inflammation is abolished during regeneration, and that of vitamin D-binding protein mRNA is converted into a decrease. The mRNAs levels of glyceraldehyde-3-phosphate dehydrogenase increase, and those for phosphoenolpyruvate carboxykinase decrease during regeneration. Ornithine transcarbamylase mRNA levels are found to exhibit negative acute-phase regulation. The pattern of transcriptional regulation is similar during inflammation and regeneration.

Follistatin concentrations in male sheep increase following sham castration/castration or injection of interleukin-1β

1996 ◽  
Vol 151 (1) ◽  
pp. 119-124 ◽  
Author(s):  
D J Phillips ◽  
M P Hedger ◽  
J R McFarlane ◽  
R Klein ◽  
I J Clarke ◽  
...  
Keyword(s):  
Acute Phase ◽  
Acute Phase Response ◽  
Interleukin 2 ◽  
Inhibitory Effect ◽  
Phase Response ◽  
Interleukin 1Β ◽  
Tnf Α ◽  
Recombinant Interleukin 2 ◽  
Factor Α ◽  
Male Sheep

Abstract Plasma follistatin (FS) concentrations were determined after castration (n=5) or sham castration (n=4) of mature rams. Both treatments resulted in a prolonged increase in FS between 7 and 19 h after surgery, which returned to pretreatment concentrations by 24 h. Tumour necrosis factor-α (TNF-α), a sensitive marker of an acute-phase response, was undetectable in plasma, indicating that the FS response was not induced by trauma due to surgery. In a second experiment, injection of castrated rams (n=4) with ovine recombinant interleukin-1β, an acute-phase mediator, resulted in a sustained rise in FS concentrations within 4 h of injection. Plasma TNF-α concentrations increased transiently within 1 h of interleukin-1β injection, indicating that an acute-phase response had been initiated. Plasma follicle-stimulating hormone (FSH) concentrations were significantly decreased at 8 and 24 h after interleukin-1β injection, strongly suggestive of an inhibitory effect of increased FS concentrations on the secretion of FSH. Injection of castrated rams (n=2) with a control preparation of recombinant interleukin-2 did not induce an acute-phase response, and plasma FS and FSH concentrations were unaffected. These data show that the testis is not a major source of circulating FS, that the increase in circulating FS following sham castration/castration is not due to an acute-phase response, but that conversely FS concentrations are modulated by the acute-phase mediator, interleukin-1β. Journal of Endocrinology (1996) 151, 119–124

Unchanged capacity of urea synthesis during acute phase response in rats

2010 ◽  
Vol 41 (1) ◽  
pp. 16-22 ◽  
Author(s):  
Karen L. Thomsen ◽  
Niels K. Aagaard ◽  
Susanne S. Nielsen ◽  
Henning Grønbaek ◽  
Niels Jessen ◽  
...  
Keyword(s):  
Acute Phase ◽  
Acute Phase Response ◽  
Phase Response ◽  
Urea Synthesis

scholarly journals Monokines regulate glycosylation of acute-phase proteins.

1987 ◽  
Vol 166 (1) ◽  
pp. 253-258 ◽  
Author(s):  
A Mackiewicz ◽  
M K Ganapathi ◽  
D Schultz ◽  
I Kushner
Keyword(s):  
Cell Line ◽  
Acute Phase ◽  
Acute Phase Response ◽  
Acute Phase Proteins ◽  
Hepatoma Cell ◽  
Phase Response ◽  
Hepatoma Cell Line ◽  
Human Hepatoma Cell ◽  
Inflammatory Stimuli ◽  
Necrosis Factor

The acute-phase response to inflammatory stimuli, characterized by increased synthesis of acute-phase proteins (APP), is often accompanied by changes in the glycosylation patterns of some of these proteins. While expression of APP genes in hepatocytes is regulated by monokines, mechanisms governing changes in glycosylation are not known. Exposure of human hepatoma cell line Hep 3B to conditioned medium from LPS-activated human monocytes and to medium from the keratocarcinoma cell line COLO-16 led to increased synthesis of alpha 1 proteinase-inhibitor and ceruloplasmin and to alterations of their glycosylation patterns similar to those seen in human serum in various inflammatory states. IL-1, tumor necrosis factor, and hepatocyte stimulating factor I increased synthesis of ceruloplasmin without alterations in the pattern of its glycosylation. These findings demonstrate that altered glycosylation seen in plasma in some inflammatory states can be explained by the effects of monokines on glycosylation in hepatocytes and that gene expression and glycosylation of some APP during the acute-phase response may be regulated by different mechanisms.

scholarly journals Acute phase proteins and their use in the diagnosis of diseases in ruminants: a review

2014 ◽  
Vol 59 (No. 4) ◽  
pp. 163-180 ◽  
Author(s):  
C. Tothova ◽  
O. Nagy ◽  
G. Kovac
Keyword(s):  
Clinical Application ◽  
Acute Phase ◽  
Acute Phase Response ◽  
Acute Phase Proteins ◽  
Phase Response ◽  
Farm Animals ◽  
Wide Range ◽  
New Biomarkers ◽  
Treatment Prognosis ◽  
Hepatic Synthesis

The acute phase response is a complex systemic early-defence system of reactions activated by trauma, infection, tissue damage, inflammation, stress or neoplasia. One of the most important elements of this response is the increased hepatic synthesis of some plasma proteins, collectively known as acute phase proteins. The discovery of these new biomarkers has allowed the clinical monitoring of different diseases; therefore, their clinical application has been studied widely in human medicine in order to improve the diagnosis, evaluation, treatment, prognosis and therapeutics of many diseases. Although a wide range of studies have been carried out to determine the usefulness of acute phase proteins in several diseases also in animals, they are still relatively under-utilised in veterinary medicine, predominantly in farm animals. The acute phase response and clinical application of acute phase proteins in ruminants are reviewed in this article, including their diagnostic use in clinical practice and application in the monitoring of treatment, which is one of the most promising practical uses of these proteins. &nbsp;

scholarly journals Suppression of DHEA sulfotransferase (Sult2A1) during the acute-phase response

2004 ◽  
Vol 287 (4) ◽  
pp. E731-E738 ◽  
Author(s):  
Min Sun Kim ◽  
Judy Shigenaga ◽  
Art Moser ◽  
Carl Grunfeld ◽  
Kenneth R. Feingold
Keyword(s):  
Acute Phase ◽  
Acute Phase Response ◽  
Hormone Receptors ◽  
Mrna Level ◽  
Pregnane X Receptor ◽  
Phase Response ◽  
Farnesoid X Receptor ◽  
Bile Acid Metabolism ◽  
Mrna Levels ◽  
Dependent Manner

The acute-phase response (APR) induces alterations in lipid metabolism, and our data suggest that this is associated with suppression of type II nuclear hormone receptors that are key regulators of fatty acid, cholesterol, and bile acid metabolism. Recently, the farnesoid X receptor (FXR), constitutive androstane receptor (CAR), and pregnane X receptor (PXR) were found to regulate DHEA sulfotransferase (Sult2A1), which plays an important role in DHEA sulfation and detoxification of bile acids. Because FXR, PXR, and CAR are suppressed during the APR, we hypothesized that Sult2A1 is downregulated during the APR. To induce the APR, mice were treated with LPS, which will then trigger the release of various cytokines, and the mRNA levels of Sult2A1 and the sulfate donor 3′-phosphoadenosine 5′-phosphosulfate synthase 2 (PAPSS2), as well as the enzyme activity of Sult2A1, were determined in the liver. We found that mRNA levels of Sult2A1 decrease in a time- and dose-dependent manner during the LPS-induced APR. Similar changes were observed in the mRNA levels of PAPSS2, the major synthase of PAPS in the liver. Moreover, hepatic Sult2A1 activity and serum levels of DHEA-sulfate (DHEA-S) were significantly decreased in LPS-treated animals. These results suggest that decreased levels or activities of FXR, PXR, and CAR during the APR could contribute to decreases in Sult2A1, resulting in decreased sulfation of DHEA and lower circulating level of DHEA-S. Finally, we found that both TNF and IL-1 caused a significant decrease in the mRNA level of Sult2A1 in Hep3B human hepatoma cells, suggesting that the proinflammatory cytokines TNF and IL-1 mediate the inhibitory effect of LPS on Sult2A1 mRNA level. Our study provides a possible mechanism by which infection and inflammation are associated with altered steroid metabolism and cholestasis.

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