Search results for "Acyltransferases"
showing 10 items of 41 documents
Evidence for PTGER4 ,PSCA, and MBOAT7 as risk genes for gastric cancer on the genome and transcriptome level
2018
Genetic associations between variants on chromosome 5p13 and 8q24 and gastric cancer (GC) have been previously reported in the Asian population. We aimed to replicate these findings and to characterize the associations at the genome and transcriptome level. We performed a fine-mapping association study in 1926 GC patients and 2012 controls of European descent using high dense SNP marker sets on both chromosomal regions. Next, we performed expression quantitative trait locus (eQTL) analyses using gastric transcriptome data from 143 individuals focusing on the GC associated variants. On chromosome 5p13 the strongest association was observed at rs6872282 (P = 2.53 x 10(-04)) and on chromosome …
Loss of function mutation in the palmitoyl-transferase HHAT leads to syndromic 46,XY disorder of sex development by impeding Hedgehog protein palmito…
2014
The Hedgehog (Hh) family of secreted proteins act as morphogens to control embryonic patterning and development in a variety of organ systems. Post-translational covalent attachment of cholesterol and palmitate to Hh proteins are critical for multimerization and long range signaling potency. However, the biological impact of lipid modifications on Hh ligand distribution and signal reception in humans remains unclear. In the present study, we report a unique case of autosomal recessive syndromic 46,XY Disorder of Sex Development (DSD) with testicular dysgenesis and chondrodysplasia resulting from a homozygous G287V missense mutation in the hedgehog acyl-transferase (HHAT) gene. This mutation…
Risk of chemotherapy-associated liver injury (CALI) in PNPLA3 p.148M allele carriers: Preliminary results of a transient elastography-based study
2019
Liver steatosis is one of the side effects of chemotherapy. The PNPLA3 p.I148M, TM6SF2 p.E167K and MBOAT7 p.G17E variants represent genetic determinants for progressive liver diseases. Here, we investigate their association with chemotherapy-associated steatosis.Prospectively, we recruited 87 patients undergoing systemic chemotherapy for gastrointestinal cancers. Hepatic fat (controlled attenuation parameter, CAP) and liver stiffness (LSM) were measured non-invasively before the initiation of chemotherapy (T0) and after at least two (T1) and four cycles (T2). Genetic variants were genotyped using allelic discrimination assays.In the final dataset (n = 60) patients demonstrated the following…
Copurification of dihydroxyacetone-phosphate acyl-transferase and other peroxisomal proteins from liver of fenofibrate-treated rats.
1997
Dihydroxyacetone-phosphate acyl-transferase (DHAP-AT), a peroxisomal membrane-bound enzyme that catalyzes the first step of ether-glycerolipid synthesis, was purified from liver of rats treated with fenofibrate, a peroxisome proliferator. The protocol first included isolation of peroxisomes, their purification through a discontinuous gradient and solubilization of membranes in CHAPS. DHAP-AT was further purified by four chromatographic steps, namely low-pressure size-exclusion, cation-exchange, hydroxylapatite and chromatofocusing. The chromatofocusing step led to a 4000-fold increase in the specific activity of DHAP-AT with respect to the liver homogenate with a yield of about 0.2%. Trypsi…
In situ hybridization of dihydroxyacetone phosphate acyltransferase, the regulating enzyme involved in plasmalogen biosynthesis
2005
International audience; In situ hybridization can be carried out using different methods. The experimenter has to choose various parameters: the type of tissue fixation, the time of incubation, and the duration of the exposure time. All these parameters are determinant for the sensitivity and the resolution of this technique. This publication of technical aspects described different experiments performed for in situ hybridization on liver tissue. We may conclude on the parameters to optimize each step of the hybridization procedure. Moreover, this technique could be transposed to the brain and applied to little structures with a light expression of DHAP-AT.
Mildronate, the inhibitor of l-carnitine transport, induces brain mitochondrial uncoupling and protects against anoxia-reoxygenation
2013
Abstract The preservation of mitochondrial function is essential for normal brain function after ischaemia-reperfusion injury. l -carnitine is a cofactor involved in the regulation of cellular energy metabolism. Recently, it has been shown that mildronate, an inhibitor of l -carnitine transport, improves neurological outcome after ischaemic damage of brain tissues. The aim of the present study was to elucidate the mitochondria targeted neuroprotective action of mildronate in the model of anoxia-reoxygenation-induced injury. Wistar rats were treated daily with mildronate ( per os ; 100 mg/kg) for 14 days. The acyl-carnitine profile was determined in the brain tissues. Mitochondrial respirati…
Involvement of plasmalogens in post-natal retinal vascular development
2014
Objective: Proper development of retinal blood vessels is essential to ensure sufficient oxygen and nutrient supplies to the retina. It was shown that polyunsaturated fatty acids (PUFAs) could modulate factors involved in tissue vascularization. A congenital deficiency in ether-phospholipids, also termed "plasmalogens'', was shown to lead to abnormal ocular vascularization. Because plasmalogens are considered to be reservoirs of PUFAs, we wished to improve our understanding of the mechanisms by which plasmalogens regulate retinal vascular development and whether the release of PUFAs by calcium-independent phospholipase A2 (iPLA2) could be involved. [br/] Methods and Results: By characterizi…
Sortase A Inhibitors: Recent Advances and Future Perspectives
2015
Here, we describe the most promising small synthetic organic compounds that act as potent Sortase A inhibitors and cater the potential to be developed as antivirulence drugs. Sortase A is a polypeptide of 206 amino acids, which catalyzes two sequential reactions: (i) thioesterification and (ii) transpeptidation. Sortase A is involved in the process of bacterial adhesion by anchoring LPXTG-containing proteins to lipid II. Sortase A inhibitors do not affect bacterial growth, but they restrain the virulence of pathogenic bacterial strains, thereby preventing infections caused by Staphylococcus aureus or other Gram-positive bacteria. The efficacy of the most promising inhibitors needs to be com…
Crystal structure of vinorine synthase, the first representative of the BAHD superfamily.
2005
Vinorine synthase is an acetyltransferase that occupies a central role in the biosynthesis of the antiarrhythmic monoterpenoid indole alkaloid ajmaline in the plant Rauvolfia. Vinorine synthase belongs to the benzylalcohol acetyl-, anthocyanin-O-hydroxy-cinnamoyl-, anthranilate-N-hydroxy-cinnamoyl/benzoyl-, deacetylvindoline acetyltransferase (BAHD) enzyme superfamily, members of which are involved in the biosynthesis of several important drugs, such as morphine, Taxol, or vindoline, a precursor of the anti-cancer drugs vincaleucoblastine and vincristine. The x-ray structure of vinorine synthase is described at 2.6-angstrom resolution. Despite low sequence identity, the two-domain structure…
l-Tyrosine β-naphthylamide is a potent competitive inhibitor of tyramine N-(hydroxycinnamoyl)transferase in vitro
2001
L-Tyrosine beta-naphthylamide, a synthetic substrate designed to measure tyrosine aminopeptidase activity, is a potent inhibitor of hydroxycinnamoyl-CoA:tyramine N-(hydroxycinnamoyl)transferase (THT) purified from elicited tobacco cell-suspension cultures. The inhibition is competitive, with the inhibitor binding reversibly to the tyramine binding site of the enzyme. Similar results were obtained with THT extracted from elicited potato cell-suspension cultures. Ki values were found to be 0.66 microM for the enzyme from tobacco and 0.3 microM for the enzyme from potato. L-Tyrosine 7-amido-4-methylcoumarin, a fluorogenic substrate for tyrosine aminopeptidases, the structure of which is close …