Effects of tumour necrosis factor on hepatic amino acid uptake

1989 ◽  
Vol 17 (6) ◽  
pp. 1045-1046 ◽  
Author(s):  
JOSEP M. ARGILÉS ◽  
FRANCISCO J. LÓPEZ-SORIANO
Keyword(s):  
Amino Acid ◽  
Tumour Necrosis Factor ◽  
Tumour Necrosis ◽  
Amino Acid Uptake ◽  
Acid Uptake ◽  
Necrosis Factor

scholarly journals The effects of tumour necrosis factor-α (cachectin) and tumour growth on hepatic amino acid utilization in the rat

1990 ◽  
Vol 266 (1) ◽  
pp. 123-126 ◽  
Author(s):  
J M Argilés ◽  
F J López-Soriano
Keyword(s):  
Amino Acid ◽  
Tumour Necrosis Factor ◽  
Tumour Necrosis ◽  
Tumour Growth ◽  
Total Amino Acid ◽  
Acute Administration ◽  
Acid Uptake ◽  
Necrosis Factor Alpha ◽  
The Individual ◽  
Necrosis Factor

The effects of acute administration of tumour necrosis factor-alpha (cachectin) (TNF-alpha) or of malignant tumour growth (Walker-256 carcinosarcoma) on hepatic availability and uptake of individual amino acids were compared. The results show that, in spite of lowering the hepatic availability of alanine, aspartate, serine, glycine and proline, the cytokine increased both the total amino acid hepatic uptake and the individual uptakes of alanine, glutamate, serine, threonine, proline, lysine and arginine, while decreasing those of leucine, isoleucine and phenylalanine. Tumour burden resulted in an increase in the hepatic availability of glutamine, threonine, glycine, lysine, leucine, isoleucine, valine and phenylalanine. Total liver amino acid uptake was unaffected, whereas the individual uptakes of alanine, threonine and proline were increased and those of glutamate, glutamine, serine and leucine were decreased. When effects of the cytokine are compared with those induced by tumour growth, there are similar increases in net utilization for alanine, proline and leucine, and a 3-fold difference in the increase observed for threonine. Unmatched effects are seen for glutamate, glutamine, aspartate, glycine, lysine, arginine, valine, phenylalanine and serine.

scholarly journals The Fn14 cytoplasmic tail binds tumour-necrosis-factor-receptor-associated factors 1, 2, 3 and 5 and mediates nuclear factor-kappaB activation

2003 ◽  
Vol 371 (2) ◽  
pp. 395-403 ◽  
Author(s):  
Sharron A.N. BROWN ◽  
Christine M. RICHARDS ◽  
Heather N. HANSCOM ◽  
Sheau-Line Y. FENG ◽  
Jeffrey A. WINKLES
Keyword(s):  
Amino Acid ◽  
Tumour Necrosis Factor ◽  
Tumour Necrosis ◽  
Cytoplasmic Tail ◽  
Luciferase Reporter ◽  
Nuclear Factor ◽  
3T3 Cells ◽  
Nih 3T3 ◽  
Necrosis Factor ◽  
Nih 3T3 Cells

Fn14 is a growth-factor-inducible immediate-early-response gene encoding a 102-amino-acid type I transmembrane protein. The human Fn14 protein was recently identified as a cell-surface receptor for the tumour necrosis factor (TNF) superfamily member named TWEAK (TNF-like weak inducer of apoptosis). In the present paper, we report that the human TWEAK extracellular domain can also bind the murine Fn14 protein. Furthermore, site-specific mutagenesis and directed yeast two-hybrid interaction assays revealed that the TNFR-associated factor (TRAF) 1, 2, 3 and 5 adaptor molecules bind the murine Fn14 cytoplasmic tail at an overlapping, but non-identical, amino acid sequence motif. We also found that TWEAK treatment of quiescent NIH 3T3 cells stimulates inhibitory κBα phosphorylation and transcriptional activation of a nuclear factor-κB (NF-κB) enhancer/luciferase reporter construct. Fn14 overexpression in transiently transfected NIH 3T3 cells also promotes NF-κB activation, and this cellular response requires an intact TRAF binding site. These results indicate that Fn14 is a functional TWEAK receptor that can associate with four distinct TRAF family members and stimulate the NF-κB transcription factor signalling pathway.

Dietary Sulphur Amino Acid Adequacy Influences Glutathione Synthesis and Glutathione-Dependent Enzymes during the Inflammatory Response to Endotoxin and Tumour Necrosis Factor-α in Rats

1997 ◽  
Vol 92 (3) ◽  
pp. 297-305 ◽  
Author(s):  
Emma A. L. Hunter ◽  
Robert F. Grimble
Keyword(s):  
Amino Acid ◽  
Food Intake ◽  
Tumour Necrosis Factor ◽  
Tumour Necrosis ◽  
Protein Diet ◽  
Glutathione Synthesis ◽  
Sulphur Amino Acid ◽  
Low Protein ◽  
Ad Libitum ◽  
Necrosis Factor

1. Glutathione concentrations in liver and lung fall when food intake or sulphur amino acid intake is inadequate. However, concentrations may be restored during inflammation, despite anorexia, provided that prior sulphur amino acid intake is adequate. 2. We studied the mechanisms of these changes by measuring the effect of sulphur amino acid and protein intake on hepatic glutathione synthesis and γ-glutamylcysteine synthetase activity, hepatic and lung glutathione concentrations, glutathione reductase and glutathione peroxidase activities in young rats given an inflammatory challenge by intraperitoneal injection of tumour necrosis factor-α or endotoxin (lipopolysaccharide). 3. Diets containing 200 g of casein and 8 g of l-cysteine/kg (normal-protein diet), or 80 g of casein and 8 g of l-cysteine, or isonitrogenous amounts of l-methionine or l-alanine (low-protein diets) were fed ad libitum to young Wistar rats for 8 days. Dietary groups were subdivided into three: one subgroup continued feeding ad libitum, a second was given tumour necrosis factor or lipopolysaccharide and killed 24 h thereafter, while the third was pair-fed to the intakes of the second subgroup for 24 h before being killed. 4. Glutathione concentrations in liver and lung were reduced in rats fed the low-protein diet containing alanine, and in all dietary groups when food intake was restricted. The inflammatory challenges restored hepatic glutathione concentrations in all groups but the diet supplemented with alanine, which had an inadequate sulphur amino acid content. In lung, restoration occurred only in animals fed the normal-protein diet. 5. The activity of γ-glutamylcysteine synthetase, which is rate limiting for glutathione synthesis, was unaffected by dietary or sulphur amino acid intake or by the inflammatory response. Substrate supply may therefore be a major determinant in glutathione synthesis in vivo. 6. Total hepatic glutathione synthesis was affected by food intake, the type and amount of sulphur amino acids in the diet and by inflammation. Total synthesis was 207, 137, 421 and 90 μmol/day for animals fed ad libitum the normal-protein diet, or low-protein diets supplemented with cysteine, methionine or alanine respectively, ad libitum. Pairfeeding resulted in values of 76, 31, 71, and 0 μmol/day respectively. After lipopolysaccharide injection, rates increased to 200, 117, 151 and 56 μmol/day respectively. 8. Reductase and peroxidase activities increased in liver and lung, when low-protein diets which contained supplemental methionine or alanine were consumed ad libitum. A reduction in food intake resulted in enzyme activity changes, which suggested that recycling of glutathione increased in lung and decreased in liver. Injection of tumour necrosis factor reversed this effect. 9. The restoration of glutathione concentrations in liver after an inflammatory challenge is closely associated with an enhanced rate of synthesis and increased recycling. The former is impaired when inadequate sulphur amino acid is consumed before the challenge. In lung, increased recycling of glutathione may help maintain concentrations when food intake is restricted, but not during inflammation.

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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