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| 1 | Human intestinal acyl-CoA synthetase 5 is sensitive to the inhibitor triacsin C显示文摘AIM:To investigate whether human acyl-CoA synthetase 5(ACSL5) is sensitive to the ACSL inhibitor triacsin C.METHODS:The ACSL isoforms ACSL1 and ACSL5 from rat as well as human ACSL5 were cloned and recombinantly expressed as 6xHis-tagged enzymes.Ni 2+-affinity purified recombinant enzymes were assayed at pH 7.5 or pH 9.5 in the presence or absence of triacsin C.In addition,ACSL5 transfected CaCo2 cells and intestinal human mucosa were monitored.ACSL5 expression in cellular systems was verified using Western blot and immunofluorescence.The ACSL assay mix included TrisHCl(pH 7.4),ATP,CoA,EDTA,DTT,MgCl 2,[9,103 H] palmitic acid,and triton X-100.The 200 μL reaction was initiated with the addition of solubilized,purified recombinant proteins or cellular lysates.Reactions were terminated after 10,30 or 60 min of incubation with Doles medium.RESULTS:Expression of soluble recombinant ACSL proteins was found after incubation with isopropyl betaD-1-thiogalactopyranoside and after ultracentrifugation these were further purified to near homogeneity with Ni 2+-affinity chromatography.Triacsin C selectively and strongly inhibited recombinant human ACSL5 protein at pH 7.5 and pH 9.5,as well as recombinant rat ACSL1(sensitive control),but not recombinant rat ACSL5(insensitive control).The IC50 for human ACSL5 was about 10 μmol/L.The inhibitory triacsin C effect was similar for different incubation times(10,30 and 60 min) and was not modified by the N-or C-terminal location of the 6xHis-tag.In order to evaluate ACSL5 sensitivity to triacsin C in a cellular environment,stable human ACSL5 CaCo2 transfectants and mechanically dissected normal human intestinal mucosa with high physiological expression of ACSL5 were analyzed.In both models,ACSL5 peak activity was found at pH 7.5 and pH 9.5,corresponding to the properties of recombinant human ACSL5 protein.In the presence of triacsin C(25 μmol/L),total ACSL activity was dramatically diminished in human ACSL5 transfectants as well as in ACSL5-rich human intestinal mucosa.CONCLUSION:The data strongly indicate that human ACSL5 is sensitive to triacsin C and does not compensate for other triacsin C-sensitive ACSL isoforms. | Elke Kaemmerer Anne Peuscher Andrea Reinartz Christian Liedtke Ralf Weiskirchen Jürgen Kopitz Nikolaus Gassler | 2011 | World Journal of Gastroenterology2011，17，44： | 3 |
| 2 | Side effects of budesonide in liver cirrhosis due to chronic autoimmune hepatitis: Influence of hepatic metabolism versus portosystemic shunts on a patient complicated with HCC显示文摘AIM: To investigate the systemic availability of budesonide in a patient with Child A drrhosis due to autoimmune hepatitis (AIH) and primary hepatocellular carcinoma, who developed serious side effects.METHODS: Serum levels of budesonide, 6β-OH-budesonide and 16α-OH-prednisolon were measured by HPLC/MS/MS;portosysternic shunt-index (SI) was determined by 99mTc nuclear imaging. All values were compared with a matched control patient without side effects.RESULTS: Serum levels of budesonide were 13-fold increased in the index patient. The ratio between serum levels of the metabolites 6β-OH-budesonide and 16α-OH-prednisolone, respectively, and serum levels of budesonide was diminished (1.0 vs. 4.0 for 6β-OH-budesonide, 4.2 vs.10.7 for 16α-OH-prednisolone). Both patients had portosystemic SI (5.7% and 3.1%) within the range of healthy subjects.CONCLUSION: Serum levels of budesonide vary up to 13-fold in AIH patients with Child A cirrhosis in the absence of relevant portosysternic shunting. Reduced hepatic metabolism, as indicated by reduced metabolite-to-drug ratio, rather than portosystemic shunting may explain systemic side effects of this drug in cirrhosis. | Andreas Geier Carsten Gartung Christoph G.Dietrich Hermann E.Wasmuth Patrick Reinartz Siegfried Matern | 2003 | World Journal of Gastroenterology2003，9，12： | 3 |
| 3 | Lipid-induced up-regulation of human acyl-CoA synthetase 5 promotes hepatocellular apoptosis显示文摘 | Andrea Reinartz Josef Ehling Andrea Leue Christian Liedtke Ursula Schneider Jürgen Kopitz Thomas Weiss Claus Hellerbrand Ralf Weiskirchen Ruth Knüchel Nikolaus Gassler | 2010 | BBA - Molecular and Cell Biology of Lipids2010，，9： | 2 |
| 4 | Lipid-induced up-regulation of human acyl-CoA synthetase 5 promotes hepatocellular apoptosis显示文摘 | Andrea Reinartz Josef Ehling Andrea Leue Christian Liedtke Ursula Schneider Jürgen Kopitz Thomas Weiss Claus Hellerbrand Ralf Weiskirchen Ruth Knüchel Nikolaus Gassler | 2010 | BBA - Molecular and Cell Biology of Lipids2010，，9： | 1 |
| 5 | Modifier-concept of colorectal carcinogenesis: Lipidomics as a technical tool in pathway analysis显示文摘In the modifier concept of intestinal carcinogenesis, lipids have been established as important variables and one focus is given to long-chain fatty acids. Increased consumption of long-chain fatty acids is in discussion to modify the development of colorectal carcinoma in humans. Saturated long-chain fatty acids, in particular, are assumed to promote carcinogenesis, whereas poly-unsaturated forms are likely to act in the opposite way. At present, the molecular mechanisms behind these effects are not well understood. Recently, it has been demonstrated by lipidomics and associated molecular techniques, that activation and metabolic channeling of long-chain fatty acids are important mechanisms to modify colorectal carcinogenesis. In this Editorial, an overview about the present concept of long-chain fatty acids and its derivatives in colorectal carcinogenesis as well as technical algorithms in lipid analysis is given. | Nikolaus Gassler Christina Klaus Elke Kaemmerer Andrea Reinartz | 2010 | World Journal of Gastroenterology2010，16，15： | 1 |
| 6 | Fatty acid binding receptors in intestinal physiology and pathophysiology显示文摘Free fatty acids are essential dietary components and recognized as important molecules in the maintenance of cellular homeostasis.In the last decade,the molecular pathways for free fatty acid sensing in the gastrointestinal tract have been further elucidated by molecular identification and functional characterization of fatty acid binding receptors.These sensing molecules belong to the family of G proteincoupled receptors.In the intestine,four important receptors have been described so far.They differ in molecular structure,ligand specificity,expression pattern,and functional properties.In this review,an overview of intestinal fatty acid binding receptors and their role in intestinal physiology and pathophysiology is given. | Elke Kaemmerer Patrick Plum Christina Klaus Ralf Weiskirchen Christian Liedtke Maximilian Adolf Angela Schippers Norbert Wagner Andrea Reinartz Nikolaus Gassler | 2010 | World Journal of Gastrointestinal Pathophysiology2010，1，5： | 0 |
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