Altered glomerular steady-state levels of tumour necrosis factor-α mRNA during nephrotic and sclerotic phases of puromycin aminonucleoside nephrosis in rats

1993 ◽  
Vol 84 (3) ◽  
pp. 349-356 ◽  
Author(s):  
Tsukasa Nakamura ◽  
Isao Ebihara ◽  
Mitsumine Fukui ◽  
Toshimasa Takahashi ◽  
Yasuhiko Tomino ◽  
...  
Keyword(s):  
Tumour Necrosis Factor ◽  
Tumour Necrosis ◽  
Glomerular Sclerosis ◽  
Mrna Levels ◽  
Tumour Necrosis Factor Α ◽  
Puromycin Aminonucleoside ◽  
Factor Α ◽  
Aminonucleoside Nephrosis ◽  
Necrosis Factor ◽  
Puromycin Aminonucleoside Nephrosis

1. We determined glomerular and medullary tumour necrosis factor-α mRNA levels in acute puromycin aminonucleoside nephrosis on days 0, 8 and 20. 2. Tumour necrosis factor-α mRNA levels were increased fourfold in glomeruli and twofold in the medulla during the nephrotic stage of acute puromycin aminonucleoside nephrosis (day 8). 3. The high tumour necrosis factor-α mRNA levels in both glomeruli and the medulla were ameliorated significantly by methylprednisolone administration. 4. Focal glomerular sclerosis was induced in rats by injection of puromycin aminonucleoside on days 0, 27, 34 and 41 and by unilateral nephrectomy on day 22. 5. The percentage of sclerosing glomeruli was 16.6% on day 48 and had increased significantly to 72.8% on day 80. 6. During the sclerotic phase of puromycin amino-nucleoside nephrosis, glomerular tumour necrosis factor-α mRNA levels increased as glomerular sclerosis progressed. On day 80, glomerular tumour necrosis factor-α mRNA levels were 13-fold higher than levels in control rats. 7. These data suggest that glomerular tumour necrosis factor-α mRNA expression is associated with the development of puromycin aminonucleoside-induced glomerular sclerosis.

Cardiac Muscle Protein Gene Expression in the Endotoxin-Treated Rat

1994 ◽  
Vol 87 (5) ◽  
pp. 539-546 ◽  
Author(s):  
D. C. Macallan ◽  
G. E. Griffin
Keyword(s):  
Cardiac Muscle ◽  
Myosin Heavy Chain ◽  
Tumour Necrosis Factor ◽  
Heavy Chain ◽  
Tumour Necrosis ◽  
Muscle Protein ◽  
Mrna Levels ◽  
Tumour Necrosis Factor Α ◽  
Factor Α ◽  
Necrosis Factor

1. Sepsis is associated with marked changes in cardiac muscle protein synthesis. Such changes may be the result of altered transcription of specific myofibrillar protein mRNAs. 2. In order to investigate myofibrillar protein gene expression, a rat model of sepsis was used. Adult rats were given a single sub-lethal dose of lipopolysaccharide by the intraperitoneal route. At various times thereafter, rats were killed and ventricular muscle was removed. RNA was extracted and transferred to nylon membranes. Changes in expression of mRNA for α- and β-myosin heavy chain, α-actin, cardiac troponin C and carbonic anhydrase III were detected by Northern hybridization. 3. After treatment with lipopolysaccharide, mRNA for β-myosin heavy chain increased to 260% of control values at 24 h and reached a maximum of 310% at 48 h. α-Myosin heavy chain mRNA levels fell to 72% of control values at 24 h. mRNA levels for α-actin, cardiac troponin C and carbonic anhydrase III remained unchanged. 4. In order to investigate the role of tumour necrosis factor-α in this process, some rats were pretreated with monoclonal antibody against tumour necrosis factor-α before receiving lipopolysaccharide. Such animals showed an absence of tumour necrosis factor-α bioactivity in plasma, but changes in myocardial protein mRNA levels were no different from those seen in animals receiving lipopolysaccharide alone. 5. The reduction in protein synthesis in cardiac muscle in sepsis does not appear to be the result of reduced expression of genes for structural or soluble muscle protein. Rather there is a paradoxical increase in β-myosin heavy chain expression, which may represent a protective mechanism. Tumour necrosis factor-α does not appear to be involved in the mediation of these changes.

scholarly journals Downregulation of zinc-α2-glycoprotein in adipose tissue and liver of obese ob/ob mice and by tumour necrosis factor-α in adipocytes

2009 ◽  
Vol 204 (2) ◽  
pp. 165-172 ◽  
Author(s):  
T Mracek ◽  
D Gao ◽  
T Tzanavari ◽  
Y Bao ◽  
X Xiao ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Protein Content ◽  
Tumour Necrosis Factor ◽  
Tumour Necrosis ◽  
Zucker Rats ◽  
Potential Candidate ◽  
Mrna Levels ◽  
Tumour Necrosis Factor Α ◽  
Factor Α ◽  
Necrosis Factor

Zinc-α2-glycoprotein (ZAG, also listed as AZGP1 in the MGI Database), a lipid-mobilising factor, has recently been suggested as a potential candidate in the modulation of body weight. We investigated the effect of increased adiposity on ZAG expression in adipose tissue and the liver and on plasma levels in obese (ob/ob) mice compared with lean siblings. The study also examined the effect of the pro-inflammatory cytokine tumour necrosis factor-α (TNFα) on ZAG expression in adipocytes. Zag mRNA levels were significantly reduced in subcutaneous (fourfold) and epididymal (eightfold) fat of ob/ob mice. Consistently, ZAG protein content was decreased in both fat depots of ob/ob mice. In the liver of obese animals, steatosis was accompanied by the fall of both Zag mRNA (twofold) and ZAG protein content (2.5-fold). Plasma ZAG levels were also decreased in obese mice. In addition, Zag mRNA was reduced in epididymal (fivefold) and retroperitoneal (fivefold) adipose tissue of obese (fa/fa) Zucker rats. In contrast to Zag expression, Tnfα mRNA levels were elevated in adipose tissue (twofold) and the liver (2.5-fold) of ob/ob mice. Treatment with TNFα reduced Zag gene expression in differentiated adipocytes, and this inhibition was chronic, occurring at 24 and 48 h following TNFα treatment. It is concluded that ZAG synthesis in adipose tissue and the liver is downregulated, as are its circulating levels, in ob/ob mice. The reduced ZAG production may advance the susceptibility to lipid accumulation in these tissues in obesity, and this could be at least in part attributable to the inhibitory effect of TNFα.

Activated tumour necrosis factor-α shedding process is associated with in-hospital complication in patients with acute myocardial infarction

2005 ◽  
Vol 108 (4) ◽  
pp. 339-347 ◽  
Author(s):  
Yudai SHIMODA ◽  
Mamoru SATOH ◽  
Motoyuki NAKAMURA ◽  
Tomonari AKATSU ◽  
Katsuhiko HIRAMORI
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Tumour Necrosis Factor ◽  
Peripheral Blood ◽  
Tumour Necrosis ◽  
Mrna Levels ◽  
Tumour Necrosis Factor Α ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor

TACE [TNF-α (tumour necrosis factor-α)-converting enzyme] plays an essential role in the shedding of TNF-α, which could affect the outcome of AMI (acute myocardial infarction). To investigate the clinical significance of the TACE–TNF-α system in AMI, we examined TACE-mediated TNF-α synthesis in PBMCs (peripheral blood mononuclear cells), which are a possible source of TNF-α in AMI. Forty-one patients with AMI and 15 healthy subjects (HS) were enrolled in the present study. PBMCs were isolated from peripheral blood on day 1 and 14 after the onset of AMI. TACE and TNF-α mRNA levels and intracellular median fluorescence intensity were measured by real-time RT (reverse transcriptase)–PCR and flow cytometry respectively. TACE-mediated TNF-α production was evaluated in cultured PBMCs with PMA, which is known to activate TACE. Spontaneous TACE and TNF-α levels were higher in AMI patients than in HS (P<0.001). TACE and TNF-α levels in PMA-stimulated PMBCs were markedly increased in AMI patients compared with HS (P<0.001). There was a positive correlation between TACE and TNF-α levels in AMI. Although spontaneous and stimulated levels of TACE and TNF-α decreased 14 days after the onset of AMI, levels in AMI patients were higher than in HS. In AMI patients with in-hospital complications (n=15; pump failure in ten, recurrent myocardial infarction in one, malignant ventricular arrhythmia in three and cardiac death in one), spontaneous and stimulated levels of TACE and TNF-α were higher than in patients without complications (P<0.01). These levels were higher in AMI patients with in-hospital complications 14 days after onset. These results demonstrate that TACE-mediated TNF-α maturation in PBMCs may play an important role in poor outcomes from AMI, suggesting that TACE may be a potential target for the inhibition of cellular TNF-α production in AMI.

Substrate specificity and inducibility of TACE (tumour necrosis factor α-converting enzyme) revisited: the Ala-Val preference, and induced intrinsic activity

2003 ◽  
Vol 70 ◽  
pp. 39-52 ◽  
Author(s):  
Roy A. Black ◽  
John R. Doedens ◽  
Rajeev Mahimkar ◽  
Richard Johnson ◽  
Lin Guo ◽  
...  
Keyword(s):  
Substrate Specificity ◽  
Recent Work ◽  
Tumour Necrosis Factor ◽  
Tumour Necrosis ◽  
Transforming Growth Factor ◽  
Intrinsic Activity ◽  
Converting Enzyme ◽  
Tumour Necrosis Factor Α ◽  
Factor Α ◽  
Necrosis Factor

Tumour necrosis factor α (TNFα)-converting enzyme (TACE/ADAM-17, where ADAM stands for a disintegrin and metalloproteinase) releases from the cell surface the extracellular domains of TNF and several other proteins. Previous studies have found that, while purified TACE preferentially cleaves peptides representing the processing sites in TNF and transforming growth factor α, the cellular enzyme nonetheless also sheds proteins with divergent cleavage sites very efficiently. More recent work, identifying the cleavage site in the p75 TNF receptor, quantifying the susceptibility of additional peptides to cleavage by TACE and identifying additional protein substrates, underlines the complexity of TACE-substrate interactions. In addition to substrate specificity, the mechanism underlying the increased rate of shedding caused by agents that activate cells remains poorly understood. Recent work in this area, utilizing a peptide substrate as a probe for cellular TACE activity, indicates that the intrinsic activity of the enzyme is somehow increased.

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