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[PMID]:29293656
[Au] Autor:Novotny J; Chandraratne S; Weinberger T; Philippi V; Stark K; Ehrlich A; Pircher J; Konrad I; Oberdieck P; Titova A; Hoti Q; Schubert I; Legate KR; Urtz N; Lorenz M; Pelisek J; Massberg S; von Brühl ML; Schulz C
[Ad] Endereço:Medizinische Klinik und Poliklinik I, Ludwig-Maximilians-Universität, Munich, Germany.
[Ti] Título:Histological comparison of arterial thrombi in mice and men and the influence of Cl-amidine on thrombus formation.
[So] Source:PLoS One;13(1):e0190728, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:AIMS: Medical treatment of arterial thrombosis is mainly directed against platelets and coagulation factors, and can lead to bleeding complications. Novel antithrombotic therapies targeting immune cells and neutrophil extracellular traps (NETs) are currently being investigated in animals. We addressed whether immune cell composition of arterial thrombi induced in mouse models of thrombosis resemble those of human patients with acute myocardial infarction (AMI). METHODS AND RESULTS: In a prospective cohort study of patients suffering from AMI, 81 human arterial thrombi were harvested during percutaneous coronary intervention and subjected to detailed histological analysis. In mice, arterial thrombi were induced using two distinct experimental models, ferric chloride (FeCl3) and wire injury of the carotid artery. We found that murine arterial thrombi induced by FeCl3 were highly concordant with human coronary thrombi regarding their immune cell composition, with neutrophils being the most abundant cell type, as well as the presence of NETs and coagulation factors. Pharmacological treatment of mice with the protein arginine deiminase (PAD)-inhibitor Cl-amidine abrogated NET formation, reduced arterial thrombosis and limited injury in a model of myocardial infarction. CONCLUSIONS: Neutrophils are a hallmark of arterial thrombi in patients suffering from acute myocardial infarction and in mouse models of arterial thrombosis. Inhibition of PAD could represent an interesting strategy for the treatment of arterial thrombosis to reduce neutrophil-associated tissue damage and improve functional outcome.
[Mh] Termos MeSH primário: Modelos Animais de Doenças
Infarto do Miocárdio/patologia
Ornitina/análogos & derivados
Trombose/patologia
[Mh] Termos MeSH secundário: Idoso
Animais
Cloretos/administração & dosagem
Vasos Coronários/patologia
Feminino
Compostos Férricos/administração & dosagem
Seres Humanos
Masculino
Camundongos
Meia-Idade
Ornitina/farmacologia
Estudos Prospectivos
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Chlorides); 0 (Ferric Compounds); 0 (N-alpha-benzoyl-N5-(2-chloro-1-iminoethyl)-L-ornithine amide); E524N2IXA3 (Ornithine); U38V3ZVV3V (ferric chloride)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180221
[Lr] Data última revisão:
180221
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180103
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0190728


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[PMID]:28867194
[Au] Autor:Ishida YI; Kayama T; Kibune Y; Nishimoto S; Koike S; Suzuki T; Horiuchi Y; Miyashita M; Itokawa M; Arai M; Ogasawara Y
[Ad] Endereço:Department of Molecular and Cellular Biochemistry, Meiji Pharmaceutical University, 2-522-1 Noshio, Kiyose, Nishitokyo, Tokyo 204-8588, Japan.
[Ti] Título:Identification of an argpyrimidine-modified protein in human red blood cells from schizophrenic patients: A possible biomarker for diseases involving carbonyl stress.
[So] Source:Biochem Biophys Res Commun;493(1):573-577, 2017 Nov 04.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Argpyrimidine (ARP) is an advanced glycation end product thought to be generated from a reaction between methylglyoxal and arginine residues in proteins. In this study, we observed marked accumulation of an approximately 56 kD protein, reactive to anti-ARP antibodies, in the red blood cells (RBCs) of some patients with refractory schizophrenia. This ARP-modified protein was purified from the blood of schizophrenic patients and identified as selenium binding protein 1 (SBP1) by LC-MS/MS. This is the first report of ARP-modified proteins accumulating in RBCs of patients with diseases involving carbonyl stress. We also observed high accumulation of ARP-modified SBP1 in the RBCs of patients with chronic kidney disease. Therefore, this modified protein may be a novel marker of carbonyl stress.
[Mh] Termos MeSH primário: Eritrócitos/metabolismo
Ornitina/análogos & derivados
Carbonilação Proteica
Pirimidinas/sangue
Esquizofrenia/sangue
Esquizofrenia/epidemiologia
Proteínas de Ligação a Selênio/sangue
[Mh] Termos MeSH secundário: Biomarcadores
Feminino
Seres Humanos
Japão/epidemiologia
Masculino
Ornitina/sangue
Prevalência
Reprodutibilidade dos Testes
Medição de Risco
Esquizofrenia/diagnóstico
Sensibilidade e Especificidade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biomarkers); 0 (Pyrimidines); 0 (SELENBP1 protein, human); 0 (Selenium-Binding Proteins); 0 (argpyrimidine); E524N2IXA3 (Ornithine)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171023
[Lr] Data última revisão:
171023
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170905
[St] Status:MEDLINE


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[PMID]:28844713
[Au] Autor:Qin H; Liu X; Li F; Miao L; Li T; Xu B; An X; Muth A; Thompson PR; Coonrod SA; Zhang X
[Ad] Endereço:State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, 211166, China.
[Ti] Título:PAD1 promotes epithelial-mesenchymal transition and metastasis in triple-negative breast cancer cells by regulating MEK1-ERK1/2-MMP2 signaling.
[So] Source:Cancer Lett;409:30-41, 2017 Nov 28.
[Is] ISSN:1872-7980
[Cp] País de publicação:Ireland
[La] Idioma:eng
[Ab] Resumo:Peptidylargininedeiminase 1 (PAD1) catalyzes protein for citrullination, and this activity has been linked to the epidermal cornification. However, a role for PAD1 in tumorigenesis, including breast cancers has not been previously explored. Here we first showed that PAD1 is overexpressed in human triple negative breast cancer (TNBC). In cultured cells and xenograft mouse models, PAD1 depletion or inhibition reduced cell proliferation, suppressed epithelial-mesenchymal transition, and prevented metastasis of MDA-MB-231 cells. These changes were correlated with a dramatic decrease in MMP2/9 expression. Furthermore, ERK1/2 and P38 MAPK signaling pathways are activated upon PAD1 silencing. Treatment with MEK1/2 inhibitor in PAD1 knockdown cells significantly recovered MMP2 expression, while inhibiting P38 activation only slightly elevated MMP9 levels. We then showed that PAD1 interacts with and citrullinates MEK1 thereby disrupting MEK1-catalyzed ERK1/2 phosphorylation, thus leading to the MMP2 overexpression. Collectively, our data indicate that PAD1 appears to promote tumorigenesis by regulating MEK1-ERK1/2-MMP2 signaling in TNBC. These results also raise the possibility that PAD1 may function as an important new biomarker for TNBC tumors and suggest that PAD1-specific inhibitors could potentially be utilized to treat metastatic breast cancer.
[Mh] Termos MeSH primário: Hidrolases/metabolismo
Neoplasias de Mama Triplo Negativas/enzimologia
Neoplasias de Mama Triplo Negativas/patologia
[Mh] Termos MeSH secundário: Animais
Linhagem Celular Tumoral
Proliferação Celular/fisiologia
Transição Epitelial-Mesenquimal
Feminino
Células HEK293
Seres Humanos
Hidrolases/antagonistas & inibidores
Hidrolases/biossíntese
MAP Quinase Quinase 1/metabolismo
Sistema de Sinalização das MAP Quinases
Células MCF-7
Metaloproteinase 2 da Matriz/metabolismo
Camundongos
Camundongos Endogâmicos BALB C
Camundongos Nus
Ornitina/análogos & derivados
Ornitina/farmacologia
Neoplasias de Mama Triplo Negativas/tratamento farmacológico
Ensaios Antitumorais Modelo de Xenoenxerto
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (N-alpha-benzoyl-N5-(2-chloro-1-iminoethyl)-L-ornithine amide); E524N2IXA3 (Ornithine); EC 2.7.12.2 (MAP Kinase Kinase 1); EC 2.7.12.2 (MAP2K1 protein, human); EC 3.- (Hydrolases); EC 3.4.24.24 (MMP2 protein, human); EC 3.4.24.24 (Matrix Metalloproteinase 2); EC 3.5.3.- (peptidylarginine deiminase type I)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171020
[Lr] Data última revisão:
171020
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170829
[St] Status:MEDLINE


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[PMID]:28695314
[Au] Autor:Regina TMR; Galluccio M; Scalise M; Pochini L; Indiveri C
[Ad] Endereço:Department DiBEST (Biologia, Ecologia, Scienze della Terra) Unit of Biochemistry and Molecular Biotechnology, University of Calabria, Via P. Bucci 4C, 87036, Arcavacata di Rende, Cosenza, Italy.
[Ti] Título:Bacterial production and reconstitution in proteoliposomes of Solanum lycopersicum CAT2: a transporter of basic amino acids and organic cations.
[So] Source:Plant Mol Biol;94(6):657-667, 2017 Aug.
[Is] ISSN:1573-5028
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:KEY MESSAGE: The vacuolar SlCAT2 was cloned, over-produced in E. coli and reconstituted in proteoliposomes. Arg, Ornithine and Lys were identified as substrates. Unexpectedly, also the organic cations Tetraethylammonium and Acetylcholine were transported indicating involvement of SlCAT2 in signaling. In land plants several transporters are involved in ion and metabolite flux across membranes of cells or intracellular organelles. The vacuolar amino acid transporter CAT2 from Solanum lycopersicum was investigated in this work. SlCAT2 was cloned from tomato flower cDNA, over-produced in Escherichia coli and purified by Nichel-chelating chromatography. For functional studies, the transporter was reconstituted in proteoliposomes. Competence of SlCAT2 for Arg transport was demonstrated measuring uptake of [ H]Arg in proteoliposomes which was trans-stimulated by internal Arg or ornithine. Uptake of [ H]Ornithine and [ H]Lys was also detected at lower efficiency with respect to [ H]Arg. Transport was activated by the presence of intraliposomal ATP suggesting regulation by the nucleotide. The prototype for organic cations tetraethylammonium (TEA) was also transported by SlCAT2. However, scarce reciprocal inhibition between TEA and Arg was found, while the biguanide metformin was able to strongly inhibit uptake of both substrates. These findings suggest that amino acids and organic cations may interact with the transporter through different functional groups some of which are common for the two types of substrates. Interestingly, reconstituted SlCAT2 showed competence for acetylcholine transport, which was also inhibited by metformin. Kinetics of Arg and Ach transport were performed from which Km values of 0.29 and 0.79 mM were derived, respectively.
[Mh] Termos MeSH primário: Proteínas de Transporte/metabolismo
Lycopersicon esculentum/metabolismo
Proteínas de Plantas/metabolismo
Proteolipídeos/metabolismo
[Mh] Termos MeSH secundário: Acetilcolina/metabolismo
Aminoácidos Básicos/metabolismo
Arginina/metabolismo
Transporte Biológico
Proteínas de Transporte/genética
Cátions/metabolismo
Clonagem Molecular
Escherichia coli/genética
Lycopersicon esculentum/genética
Lisina/metabolismo
Ornitina/metabolismo
Proteínas de Plantas/genética
Proteínas de Plantas/isolamento & purificação
Proteínas Recombinantes/genética
Proteínas Recombinantes/isolamento & purificação
Tetraetilamônio/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Amino Acids, Basic); 0 (Carrier Proteins); 0 (Cations); 0 (Plant Proteins); 0 (Proteolipids); 0 (Recombinant Proteins); 0 (proteoliposomes); 66-40-0 (Tetraethylammonium); 94ZLA3W45F (Arginine); E524N2IXA3 (Ornithine); K3Z4F929H6 (Lysine); N9YNS0M02X (Acetylcholine)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170814
[Lr] Data última revisão:
170814
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170712
[St] Status:MEDLINE
[do] DOI:10.1007/s11103-017-0632-6


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[PMID]:28679527
[Au] Autor:Macedo JP; Currier RB; Wirdnam C; Horn D; Alsford S; Rentsch D
[Ad] Endereço:Institute of Plant Sciences, University of Bern, Bern, Switzerland.
[Ti] Título:Ornithine uptake and the modulation of drug sensitivity in .
[So] Source:FASEB J;31(10):4649-4660, 2017 Oct.
[Is] ISSN:1530-6860
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:, protozoan parasites that cause human African trypanosomiasis (HAT), depend on ornithine uptake and metabolism by ornithine decarboxylase (ODC) for survival. Indeed, ODC is the target of the WHO "essential medicine" eflornithine, which is antagonistic to another anti-HAT drug, suramin. Thus, ornithine uptake has important consequences in , but the transporters have not been identified. We describe these amino acid transporters (AATs). In a heterologous expression system, TbAAT10-1 is selective for ornithine, whereas TbAAT2-4 transports both ornithine and histidine. These AATs are also necessary to maintain intracellular ornithine and polyamine levels in , thereby decreasing sensitivity to eflornithine and increasing sensitivity to suramin. Consistent with competition for histidine, high extracellular concentrations of this amino acid phenocopied a TbAAT2-4 genetic defect. Our findings established TbAAT10-1 and TbAAT2-4 as the parasite ornithine transporters, one of which can be modulated by histidine, but both of which affect sensitivity to important anti-HAT drugs.-Macedo, J. P., Currier, R. B., Wirdnam, C., Horn, D., Alsford, S., Rentsch, D. Ornithine uptake and the modulation of drug sensitivity in .
[Mh] Termos MeSH primário: Antineoplásicos/farmacologia
Ornitina/metabolismo
Trypanosoma brucei brucei/efeitos dos fármacos
Tripanossomíase Africana/metabolismo
[Mh] Termos MeSH secundário: Animais
Eflornitina/farmacologia
Seres Humanos
Ornitina Descarboxilase/efeitos dos fármacos
Ornitina Descarboxilase/genética
Poliaminas/metabolismo
Trypanosoma brucei brucei/isolamento & purificação
Tripanossomíase Africana/tratamento farmacológico
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Polyamines); E524N2IXA3 (Ornithine); EC 4.1.1.17 (Ornithine Decarboxylase); ZQN1G5V6SR (Eflornithine)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171019
[Lr] Data última revisão:
171019
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170707
[St] Status:MEDLINE
[do] DOI:10.1096/fj.201700311R


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[PMID]:28592010
[Au] Autor:Guan HZ; Ding Y; Li DX; Dong H; Song JQ; Jin Y; Zhu ZJ; Sun LY; Yang YL
[Ad] Endereço:Department of Neonatology, Shanxi Provincial Children's Hospital, Taiyuan 030013, China.
[Ti] Título:[Clinical diagnosis and treatment of three cases with hyperornithinemia-hyperammonemia-homocitrullinuria syndrome].
[So] Source:Zhonghua Er Ke Za Zhi;55(6):428-433, 2017 Jun 02.
[Is] ISSN:0578-1310
[Cp] País de publicação:China
[La] Idioma:chi
[Ab] Resumo:To study the clinical characteristics, methods of diagnosis and treatment of hyperornithinemia-hyperammonemia- homocitrullinuria (HHH) syndrome. From July 2011 to August 2016, 3 Chinese patients with HHH syndrome were enrolled in this study. The clinical course, biochemical features, brain MRI findings, and gene mutations were analyzed. The three patients' age at onset of symptoms was 3 months to 7 years, and the age of diagonosis was 3 years and 10 months to 9 years and 10 months. All of them presented with intolerance to protein-rich foods from the infant period, development retardation and abnormal posture. Case 1 and 2 had moderate mental retardation. Serum ammonia 25-276 µmol/L (reference range<60 µmol/L), alanine aminotransferase (ALT) 20-139 IU/L (reference range 9-50 IU/L), ornithine 29.12-99.44 µmol/L(reference range 15-100 µmol/L), urinary orotic acid 1.49-29.75 mmol/mol Cr (reference range 0-7 mmol/mol Cr), uracil 6.09-103.97 mmol/mol Cr (reference range 0-1.5 mmol/mol Cr). The cranial MRI revealed lesions in the basal ganglia, abnormal white matter signal, progressive demyelination and cerebral atrophy. On their SLC25A15 gene, a novel homozygous missense mutation c. 416A>G (p.E139G) was identified in case 1, a known pathogenic homozygous nonsense mutation c. 535C>T was found in case 2 and 3. Liver transplantation had been performed when case 1 was 6 years old. Significant improvements were observed in dietary habit, mental and motor functions, and biochemical parameters. After the dietary intervention with the supplements of arginine, L-carnitine, case 2 was improved, spastic paraplegia of case 3 had no mitigation. Liver transplant was recommended. HHH syndrome has an aversion to protein-rich food, and the patients have recurrent vomiting and progressive neurological dysfunction. Clinical diagnosis of HHH syndrome is difficult and patients may present with incomplete biochemical phenotype. The genetic analysis is key for the diagnosis. Depending on their condition, individuals with HHH syndrome can be treated with a low-protein diet, drugs and liver transplantation.
[Mh] Termos MeSH primário: Dieta com Restrição de Proteínas
Hiperamonemia/diagnóstico
Mutação
Ornitina/deficiência
Fenótipo
Distúrbios Congênitos do Ciclo da Ureia/diagnóstico
[Mh] Termos MeSH secundário: Arginina
Grupo com Ancestrais do Continente Asiático
Carnitina
Criança
Pré-Escolar
Testes Genéticos
Homozigoto
Seres Humanos
Lactente
Ornitina/uso terapêutico
Ácido Orótico
Proteínas
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Proteins); 61H4T033E5 (Orotic Acid); 94ZLA3W45F (Arginine); E524N2IXA3 (Ornithine); S7UI8SM58A (Carnitine)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170807
[Lr] Data última revisão:
170807
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170609
[St] Status:MEDLINE
[do] DOI:10.3760/cma.j.issn.0578-1310.2017.06.007


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[PMID]:28570637
[Au] Autor:Aguilera S; Alvarez-Morales A; Murillo J; Hernández-Flores JL; Bravo J; De la Torre-Zavala S
[Ad] Endereço:Laboratorio Integral de Investigación en Alimentos. CONACYT-Instituto Tecnológico de Tepic, Tepic, Nayarit, México.
[Ti] Título:Temperature-mediated biosynthesis of the phytotoxin phaseolotoxin by Pseudomonas syringae pv. phaseolicola depends on the autoregulated expression of the phtABC genes.
[So] Source:PLoS One;12(6):e0178441, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Pseudomonas syringae pv. phaseolicola produces phaseolotoxin in a temperature dependent manner, being optimally synthesized between 18°C and 20°C, while no detectable amounts are present above 28°C. The Pht cluster, involved in the biosynthesis of phaseolotoxin, contains 23 genes that are organized in five transcriptional units. The function of most of the genes from the Pht cluster is still unknown and little information about the regulatory circuitry leading to expression of these genes has been reported. The purpose of the present study was to investigate the participation of pht genes in the regulation of the operons coded into the Pht cluster. We conducted Northern blot, uidA fusions and reverse transcription-PCR assays of pht genes in several mutants unable to produce phaseolotoxin. This allowed us to determine that, in P. syringae pv. phaseolicola NPS3121, genes phtABC are essential to prevent their own expression at 28°C, a temperature at which no detectable amounts of the toxin are present. We obtained evidence that the phtABC genes also participate in the regulation of the phtD, phtM and phtL operons. According to our results, we propose that PhtABC and other Pht product activities could be involved in the synthesis of the sulfodiaminophosphinyl moiety of phaseolotoxin, which indirectly could be involved in the transcriptional regulation of the phtA operon.
[Mh] Termos MeSH primário: Genes de Plantas
Ornitina/análogos & derivados
Pseudomonas syringae/metabolismo
Temperatura Ambiente
[Mh] Termos MeSH secundário: Mutação
Ornitina/biossíntese
Pseudomonas syringae/genética
Reação em Cadeia da Polimerase Via Transcriptase Reversa
Transcrição Genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
62249-77-8 (phaseolotoxin); E524N2IXA3 (Ornithine)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170926
[Lr] Data última revisão:
170926
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170602
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0178441


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[PMID]:28559406
[Au] Autor:Nakaminami H; Chen C; Truong-Bolduc QC; Kim ES; Wang Y; Hooper DC
[Ad] Endereço:Division of Infectious Diseases, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
[Ti] Título:Efflux Transporter of Siderophore Staphyloferrin A in Staphylococcus aureus Contributes to Bacterial Fitness in Abscesses and Epithelial Cells.
[So] Source:Infect Immun;85(8), 2017 Aug.
[Is] ISSN:1098-5522
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The siderophores staphyloferrin A (SA) and staphyloferrin B (SB) of are essential for iron acquisition in the iron-restricted environment of the host, such as in subcutaneous abscesses. SA and SB are secreted by SfaA and SbnD transporters, respectively. To assess the further function of SfaA and SbnD in fitness, we tested its effect on murine abscess models and intracellular replication in epithelial cells. Bacterial fitness in abscesses and in epithelial cells was studied, by comparing the parental strains RN6390 and MW2 and their Δ and Δ mutants using competition assays in a murine abscess model and invasion and replication assays with human lung adenocarcinoma cell line A549. In the murine abscess model using equal inocula of a Δ or Δ mutant and the wild-type RN6390 strain, the Δ mutant exhibited growth defects of 2.2-fold. Additionally, replication of the Δ mutant within A549 cells was decreased 3.0-fold. In complementation experiments, the Δ mutant carrying plasmid-borne restored the growth fitness in abscesses and epithelial cells. The Δ mutant, in contrast, showed no growth defect in either abscesses or epithelial cells. Our findings demonstrate that the efflux transporter of the siderophore SA contributes to the ability of to replicate in abscesses and epithelial cells. Furthermore, fitness of in these sites of replication is not compromised by the absence of transporter SbnD.
[Mh] Termos MeSH primário: Abscesso/microbiologia
Citratos/metabolismo
Células Epiteliais/microbiologia
Aptidão Genética
Ornitina/análogos & derivados
Staphylococcus aureus/genética
Staphylococcus aureus/fisiologia
[Mh] Termos MeSH secundário: Células A549
Animais
Proteínas de Bactérias/genética
Regulação Bacteriana da Expressão Gênica
Teste de Complementação Genética
Seres Humanos
Ferro/metabolismo
Proteínas de Membrana Transportadoras/metabolismo
Camundongos
Mutação
Ornitina/metabolismo
Plasmídeos
Sideróforos/metabolismo
Infecções Estafilocócicas/microbiologia
Staphylococcus aureus/crescimento & desenvolvimento
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Bacterial Proteins); 0 (Citrates); 0 (Membrane Transport Proteins); 0 (Siderophores); 127902-98-1 (staphyloferrin A); E1UOL152H7 (Iron); E524N2IXA3 (Ornithine)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170807
[Lr] Data última revisão:
170807
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170601
[St] Status:MEDLINE


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[PMID]:28528213
[Au] Autor:Makins C; Whitelaw DA; McGregor M; Petit A; Mothersole RG; Prosser KE; Wolthers KR
[Ad] Endereço:Department of Chemistry, University of British Columbia, 3247 University Way, Kelowna, BC V1V 1V7, Canada.
[Ti] Título:Optimal electrostatic interactions between substrate and protein are essential for radical chemistry in ornithine 4,5-aminomutase.
[So] Source:Biochim Biophys Acta;1865(8):1077-1084, 2017 08.
[Is] ISSN:0006-3002
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Ornithine 4,5-aminomutase (OAM) from Clostridium sticklandii is an adenosylcobalamin (AdoCbl) and pyridoxal 5'-phosphate (PLP)-dependent enzyme that catalyzes a 1,2-amino shift, interconverting d-ornithine and 2S, 4R-diaminopentanoate. The reaction occurs via a radical-based mechanism whereby a PLP-bound substrate radical undergoes intramolecular isomerization via an azacyclopropylcarbinyl radical intermediate. Herein, we investigated the catalytic role of active site residues that form non-covalent interactions with PLP and/or substrate, d-ornithine. Kinetic analyses revealed that residues that form salt bridges to the α-carboxylate (R297) or the α-amine (E81) of d-ornithine are most critical for OAM activity as conservative substitutions of these residues results in a 300-600-fold reduction in catalytic turnover and a more pronounced 1000- to 14,000-fold decrease in catalytic efficiency. In contrast, mutating residues that solely interact with the PLP cofactor led to more modest decreases (10-60-fold) in k and k /K . All but one variant (S162A) elicited an increase in the kinetic isotope effect on k and k /K with d,l-ornithine-3,3,4,4,5,5-d as the substrate, which indicates that hydrogen atom abstraction is more rate determining. Electron paramagnetic resonance spectra of the variants reveal that while the substitutions decrease the extent of CoC bond homolysis, they do not affect the structural integrity of the active site. Our experimental results, discussed in context with published computational work, suggests that the protonation state of the PLP cofactor has less of a role in radical-mediated chemistry compared to electrostatic interactions between the substrate and protein.
[Mh] Termos MeSH primário: Transferases Intramoleculares/metabolismo
Ornitina/metabolismo
[Mh] Termos MeSH secundário: Biocatálise
Domínio Catalítico/fisiologia
Clostridium sticklandii/metabolismo
Espectroscopia de Ressonância de Spin Eletrônica/métodos
Cinética
Conformação Proteica
Eletricidade Estática
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
E524N2IXA3 (Ornithine); EC 5.4.- (Intramolecular Transferases); EC 5.4.3.5 (ornithine 5,4-aminomutase)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170926
[Lr] Data última revisão:
170926
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170522
[St] Status:MEDLINE


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[PMID]:28513740
[Au] Autor:Ho YY; Nakato J; Mizushige T; Kanamoto R; Tanida M; Akiduki S; Ohinata K
[Ad] Endereço:Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Gokasho Uji, Kyoto 611-0011, Japan. ohinata@kais.kyoto-u.ac.jp.
[Ti] Título:l-Ornithine stimulates growth hormone release in a manner dependent on the ghrelin system.
[So] Source:Food Funct;8(6):2110-2114, 2017 Jun 01.
[Is] ISSN:2042-650X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:We found that intraduodenal administration of l-ornithine (l-Orn) stimulates growth hormone (GH) secretion in Wistar rats, and then investigated its mechanism. GH-releasing activity after intraduodenal administration of l-Orn was blocked by [d-Lys ]-GHRP-6, an antagonist of the ghrelin receptor; however, l-Orn (100 µM) has no affinity for the ghrelin receptor, suggesting that the GH-releasing activity of l-Orn is mediated via ghrelin release and activation of the ghrelin receptor. Intraduodenally administered l-Orn increased ghrelin mRNA expression in the duodenum but not in the stomach or hypothalamus. In addition, l-Orn-induced GH-releasing activity was inhibited by propranolol, an antagonist of ß-adrenergic receptor, which is known to be coupled to ghrelin release. In conclusion, intraduodenally administered l-Orn stimulates GH secretion through the sympathetic nervous and ghrelin systems.
[Mh] Termos MeSH primário: Grelina/metabolismo
Hormônio do Crescimento/metabolismo
Ornitina/metabolismo
[Mh] Termos MeSH secundário: Animais
Duodeno/metabolismo
Hipotálamo/metabolismo
Masculino
Ratos
Ratos Wistar
Receptores de Grelina/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Ghrelin); 0 (Receptors, Ghrelin); 9002-72-6 (Growth Hormone); E524N2IXA3 (Ornithine)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170814
[Lr] Data última revisão:
170814
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170518
[St] Status:MEDLINE
[do] DOI:10.1039/c7fo00309a



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