scholarly journals Proteolytic release of keratinocyte transglutaminase

1990 ◽  
Vol 265 (2) ◽  
pp. 351-357 ◽  
Author(s):  
R H Rice ◽  
X Rong ◽  
R Chakravarty
Keyword(s):  
Fatty Acid ◽  
Cultured Cells ◽  
Limited Proteolysis ◽  
Terminal Differentiation ◽  
Human Keratinocytes ◽  
Post Translational Modification ◽  
Catalytically Active ◽  
Endogenous Release ◽  
Acid Esterification ◽  
Active Fragment

Human keratinocytes express a particulate transglutaminase that can be released from the membrane by limited proteolysis with trypsin or plasmin to yield a form that is congruent to 80 kDa. The enzyme from cultured cells was also releasable by endogenous proteolysis to yield a catalytically active fragment of congruent to 80 kDa. Endogenous release was strongly dependent upon temperature and Ca2+ concentration and was inhibited by iodoacetate, but not by leupeptin, antipain or phenylmethanesulphonyl fluoride. These phenomena raise the possibility of partial translocation of transglutaminase activity to the cytoplasm by proteolysis to which the enzyme is subject during terminal differentiation. In addition, hydrodynamic measurements showed that the endogenously released enzyme was monomeric in solution (79 kDa), whereas that solubilized by hydroxylamine without proteolysis appeared dimeric (190 kDa). The latter dimeric state may reflect either an altered conformation of the enzyme or post-translational modification beyond fatty acid esterification.

scholarly journals Fatty acid acylation of proteins in cultured cells.

1980 ◽  
Vol 255 (21) ◽  
pp. 10021-10024 ◽  
Author(s):  
M.J. Schlesinger ◽  
A.I. Magee ◽  
M.F. Schmidt
Keyword(s):  
Fatty Acid ◽  
Cultured Cells

scholarly journals Insulin-independent regulation of hepatic triglyceride synthesis by fatty acids

2015 ◽  
Vol 112 (4) ◽  
pp. 1143-1148 ◽  
Author(s):  
Daniel F. Vatner ◽  
Sachin K. Majumdar ◽  
Naoki Kumashiro ◽  
Max C. Petersen ◽  
Yasmeen Rahimi ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Fatty Acids ◽  
Fatty Acid ◽  
Insulin Signaling ◽  
Plasma Fatty Acid ◽  
Hepatic Triglyceride ◽  
Triglyceride Synthesis ◽  
Hepatic Glucose ◽  
Acid Esterification ◽  
Fatty Acid Esterification

A central paradox in type 2 diabetes is the apparent selective nature of hepatic insulin resistance—wherein insulin fails to suppress hepatic glucose production yet continues to stimulate lipogenesis, resulting in hyperglycemia, hyperlipidemia, and hepatic steatosis. Although efforts to explain this have focused on finding a branch point in insulin signaling where hepatic glucose and lipid metabolism diverge, we hypothesized that hepatic triglyceride synthesis could be driven by substrate, independent of changes in hepatic insulin signaling. We tested this hypothesis in rats by infusing [U-13C] palmitate to measure rates of fatty acid esterification into hepatic triglyceride while varying plasma fatty acid and insulin concentrations independently. These experiments were performed in normal rats, high fat-fed insulin-resistant rats, and insulin receptor 2′-O-methoxyethyl chimeric antisense oligonucleotide-treated rats. Rates of fatty acid esterification into hepatic triglyceride were found to be dependent on plasma fatty acid infusion rates, independent of changes in plasma insulin concentrations and independent of hepatocellular insulin signaling. Taken together, these results obviate a paradox of selective insulin resistance, because the major source of hepatic lipid synthesis, esterification of preformed fatty acids, is primarily dependent on substrate delivery and largely independent of hepatic insulin action.

scholarly journals Are STATS Arginine-methylated?

2005 ◽  
Vol 280 (23) ◽  
pp. 21700-21705 ◽  
Author(s):  
Waraporn Komyod ◽  
Uta-Maria Bauer ◽  
Peter C. Heinrich ◽  
Serge Haan ◽  
Iris Behrmann
Keyword(s):  
Arginine Methylation ◽  
Signaling Cascades ◽  
Post Translational Modification ◽  
Protein Arginine Methyltransferases ◽  
Stat Proteins ◽  
Fibrosarcoma Cells ◽  
Catalytically Active ◽  
Interferon Resistance ◽  
Stat Pathway

Transcription factors of the STAT (signal transducer and activator of transcription) family are important in signal transduction of cytokines. They are subject to post-translational modification by phosphorylation on tyrosine and serine residues. Recent evidence suggested that STATs are methylated on a conserved arginine residue within the N-terminal region. STAT arginine methylation has been described to be important for STAT function and loss of arginine methylation was discussed to be involved in interferon resistance of cancer cells. Here we provide several independent lines of evidence indicating that the issue of arginine methylation of STATs has to be reassessed. First, we show that treatment of melanoma and fibrosarcoma cells with inhibitors used to suppress methylation (N-methyl-2-deoxyadenosine, adenosine, dl-homocysteine) had profound and rapid effects on phosphorylation of STAT1 and STAT3 but also on p38 and Erk signaling cascades which are known to cross-talk with the Jak/STAT pathway. Second, we show that anti-methylarginine antibodies did not precipitate specifically STAT1 or STAT3. Third, we show that mutation of Arg31 to Lys led to destabilization of STAT1 and STAT3, implicating an important structural role of Arg31. Finally, purified catalytically active protein arginine methyltransferases (PRMT1, -2, -3, -4, and -6) did not methylate STAT proteins, and cotransfection with PRMT1 did not affect STAT1-controlled reporter gene activity. Taken together, our data suggest the absence of arginine methylation of STAT1 and STAT3.

scholarly journals Identification of a second human acetyl-CoA carboxylase gene

1996 ◽  
Vol 316 (3) ◽  
pp. 915-922 ◽  
Author(s):  
Jane WIDMER ◽  
Katherine S. FASSIHI ◽  
Susannah C. SCHLICHTER ◽  
Kate S. WHEELER ◽  
Barbara E. CRUTE ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Biosynthesis ◽  
Cultured Cells ◽  
Regulatory Control ◽  
Chromosome 17 ◽  
Acid Oxidation ◽  
Acetyl Coa Carboxylase ◽  
Acetyl Coa ◽  
Specific Expression ◽  
Mrna Tissue Distribution

Acetyl-CoA carboxylase (ACC), an important enzyme in fatty acid biosynthesis and a regulator of fatty acid oxidation, is present in at least two isoenzymic forms in rat and human tissues. Previous work has established the existence of a 265000 Da enzyme in both the rat and human (RACC265; HACC265) and a higher-molecular-mass species (275000–280000 Da) in the same species (RACC280; HACC275). An HACC265 gene has previously been localized to chromosome 17. In the present study, we report cloning of a partial-length human cDNA sequence which appears to correspond to HACC275 and its rat homologue, RACC280, as judged by mRNA tissue distribution and cell-specific regulation of mRNA/protein expression. The gene encoding this isoenzymic form of ACC has been localized to the long arm of human chromosome 12. Thus, ACC is represented in a multigene family in both rodents and humans. The newly discovered human gene and its rat homologue appear to be under different regulatory control to the HACC265 gene, as judged by tissue-specific expression in vivo and by independent modulation in cultured cells in vitro.

Abstract 282: Adropin Enhancement of Cardiac Insulin Sensitivity and Inhibition of Fatty Acid Oxidation are Associated With Improvement of Cardiac Function and Efficiency in Hearts From Fasted Mice

2016 ◽  
Vol 119 (suppl_1) ◽  
Author(s):  
Tariq R Altamimi ◽  
Arata Fukushima ◽  
Liyan Zhang ◽  
Su Gao ◽  
Abhishek Gupta ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Diabetic Cardiomyopathy ◽  
Insulin Signaling ◽  
Plasma Levels ◽  
Acid Oxidation ◽  
Post Translational Modification ◽  
Cardiac Efficiency ◽  
Oxidation Rates ◽  
Cardiac Energy

Impaired cardiac insulin signaling and high cardiac fatty acid oxidation rates are characteristics of diabetic cardiomyopathy. Potential roles for liver-derived metabolic factors in mediating cardiac energy homeostasis are underappreciated. Plasma levels of adropin, a liver secreted peptide, increase during feeding and decrease during fasting and diabetes. In skeletal muscle, adropin preferentially promotes glucose over fatty acid oxidation. We therefore determined what effect adropin has on cardiac energy metabolism, insulin signaling and cardiac efficiency. C57Bl/6 mice were fasted to accentuate the differences in adropin plasma levels between animals injected 3 times over 24 hr with either vehicle or adropin (450 nmol/kg i.p.). Despite fasting-induced predominance of fatty acid oxidation measured in isolated working hearts, insulin inhibition of fatty acid oxidation was re-established in adropin-treated mice (from 1022±143 to 517±56 nmol. g dry wt -1 . min -1 , p <0.05) compared to vehicle-treated mice (from 757±104 to 818±103 nmol. g dry wt -1 . min -1 ). Adropin-treated mice hearts showed higher cardiac work over the course of perfusion (p<0.05 vs. vehicle), which was accompanied by improved cardiac efficiency and enhanced phosphorylation of insulin signaling enzymes (tyrosine-IRS-1, AS160, p<0.05). Acute addition of adropin (2nM) to isolated working hearts from non-fasting mice showed a robust stimulation of glucose oxidation compared to vehicle-treated hearts (3025±401 vs 1708±292 nmol. g dry wt -1 . min -1 , p<0.05, respectively) with a corresponding inhibition of palmitate oxidation (325±61 vs 731±160 nmol. g dry wt -1 . min -1 , p<0.05, respectively), even in the presence of insulin. Acute adropin addition to hearts also increased IRS-1 tyrosine-phosphorylation as well as Akt, and GSK3β phosphorylation (p<0.05), suggesting acute receptor- and/or post-translational modification-mediated mechanisms. These results suggest adropin as a putative candidate for the treatment of diabetic cardiomyopathy.

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