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Altered tyrosine metabolism

Hannaneh Tashackori, Mohsen Sharifi, Najmeh Ahmadian Chashmi, Mehrdad Behmanesh, Naser Safaie
Elicitation of Linum album hairy roots by Piriformospora indica cell wall induced the target genes and specific metabolites in phenylpropanoid pathway and shifted the amino acid metabolism toward the phenolic compound production. Plants have evolved complex mechanisms to defend themselves against various biotic stresses. One of these responses is the production of metabolites that act as defense compounds. Manipulation of plant cell cultures by biotic elicitors is a useful strategy for improving the production of valuable secondary metabolites...
August 14, 2018: Planta
Manasa K Nayak, Nirav Dhanesha, Prakash Doddapattar, Omar Rodriguez, Vijay K Sonkar, Sanjana Dayal, Anil K Chauhan
Resting platelets rely on oxidative phosphorylation (OXPHOS) and aerobic glycolysis (conversion of glucose to lactate in the presence of oxygen) to generate adenosine triphosphate, whereas activated platelets exhibit a high level of aerobic glycolysis, suggesting the existence of metabolic flexibility in platelets. Mitochondrial pyruvate dehydrogenase kinases (PDK 1-4) play a pivotal role in metabolic flexibility by inhibiting pyruvate dehydrogenase complex. We determined whether metabolic reprogramming, diverting metabolism from aerobic glycolysis back to OXPHOS, would inhibit platelet function...
August 14, 2018: Blood Advances
Michaeline L Hebron, Monica Javidnia, Charbel E-H Moussa
Tau hyperphosphorylation is a critical factor in neurodegenerative diseases, including dementia and Parkinsonism. Existing animal models of tauopathies express tau in neurons within the forebrain and do not often show tau accumulation in the brainstem and astrocytes. This study aims to understand the effects of differential regional expression of tau on neurotransmitter balance in the brain. To obtain an animal model that expresses tau in the brainstem, we bred hemizygous mice that express P301L tau (TauP301L) and detected hyper-phosphorylated tau (p-tau) predominantly in the hippocampus, cortex, brainstem and thalamus...
August 15, 2018: Journal of the Neurological Sciences
Haizea Ziarrusta, Leire Mijangos, Sergio Picart-Armada, Mireia Irazola, Alexandre Perera-Lluna, Aresatz Usobiaga, Ailette Prieto, Nestor Etxebarria, Maitane Olivares, Olatz Zuloaga
The extensive use of the organic UV filter oxybenzone has led to its ubiquitous occurrence in the aquatic environment, causing an ecotoxicological risk to biota. Although some studies reported adverse effects, such as reproductive toxicity, further research needs to be done in order to assess its molecular effects and mechanism of action. Therefore, in the present work, we investigated metabolic perturbations in juvenile gilt-head bream (Sparus aurata) exposed over 14 days via the water to oxybenzone (50 mg/L)...
August 4, 2018: Chemosphere
Da Jung Kim, Seonghae Yoon, Sang Chun Ji, Jinho Yang, Yoon-Keun Kim, SeungHwan Lee, Kyung-Sang Yu, In-Jin Jang, Jae-Yong Chung, Joo-Youn Cho
Ursodeoxycholic acid (UDCA) is a metabolic by-product of intestinal bacteria, showing hepatoprotective effects. However, its underlying molecular mechanisms remain unclear. The purpose of this study was to elucidate the action mechanisms underlying the protective effects of UDCA and vitamin E against liver dysfunction using metabolomics and metagenomic analysis. In this study, we analysed blood and urine samples from patients with obesity and liver dysfunction. Nine patients were randomly assigned to receive UDCA (300 mg twice daily), and 10 subjects received vitamin E (400 IU twice daily) for 8 weeks...
August 8, 2018: Scientific Reports
Elizabeth K Wiese, Taro Hitosugi
The Warburg Effect, or aerobic glycolysis, is one of the major metabolic alterations observed in cancer. Hypothesized to increase a cell's proliferative capacity via regenerating NAD+ , increasing the pool of glycolytic biosynthetic intermediates, and increasing lactate production that affects the tumor microenvironment, the Warburg Effect is important for the growth and proliferation of tumor cells. The mechanisms by which a cell acquires the Warburg Effect phenotype are regulated by the expression of numerous oncogenes, including oncogenic tyrosine kinases...
2018: Frontiers in Cell and Developmental Biology
Liangcai Zhao, Minjian Dong, Dan Wang, Mengqian Ren, Yongquan Zheng, Hong Zheng, Chen Li, Hongchang Gao
Cognitive dysfunction is a central nervous system (CNS) complication of diabetes mellitus (DM) that is characterized by impaired memory and cognitive ability. An in-depth understanding of metabolic alterations in the brain associated with DM will facilitate our understanding of the pathogenesis of cognitive dysfunction. The present study used an in vitro culture of primary neurons in a high-glucose (HG) environment to investigate characteristic alterations in neuron metabolism using nuclear magnetic resonance (NMR)-based metabonomics...
2018: Frontiers in Cellular Neuroscience
A S Davison, J A Harrold, G Hughes, B P Norman, J Devine, J Usher, A T Hughes, M Khedr, J A Gallagher, A M Milan, Halford J C G, L R Ranganath
OBJECTIVE: Concerns exist over hypertyrosinaemia that is observed following treatment with nitisinone. It has been suggested that tyrosine may compete with tryptophan for uptake into the central nervous system, and or inhibit tryptophan hydroxylase activity reducing serotonin production. At the National Alkaptonuria (AKU) Centre nitisinone is being used off-licence to treat AKU, and there is uncertainty over whether hypertyrosinaemia may alter mood. Herein results from clinical and biochemical assessments of depression in patients with AKU before and after treatment with nitisinone are presented...
July 19, 2018: Molecular Genetics and Metabolism
Francesca Monteleone, Simona Taverna, Riccardo Alessandro, Simona Fontana
BACKGROUND: Chronic myelogenous leukemia (CML) is a myeloproliferative disorder caused by expression of the chimeric BCR-ABL tyrosine kinase oncogene, resulting from the t(9;22) chromosomal translocation. Imatinib (gleevec, STI-571) is a selective inhibitor of BCR-ABL activity highly effective in the treatment of CML. However, even though almost all CML patients respond to treatment with imatinib or third generation inhibitors, these drugs are not curative and need to be taken indefinitely or until patients become resistant...
July 25, 2018: Journal of Experimental & Clinical Cancer Research: CR
Anastasia Tsagianni, Wendy M Mars, Bharat Bhushan, William C Bowen, Anne Orr, John Stoops, Shirish Paranjpe, George C Tseng, Silvia Liu, George K Michalopoulos
MET and epidermal growth factor receptor (EGFR) tyrosine kinases are crucial for liver regeneration and normal hepatocyte function. Recently, we demonstrated that in mice, combined inhibition of these two signaling pathways abolished liver regeneration after hepatectomy, with subsequent hepatic failure and death at 15 to 18 days after resection. Morbidity was associated with distinct and specific alterations in important downstream signaling pathways that led to decreased hepatocyte volume, reduced proliferation, and shutdown of many essential hepatocyte functions, such as fatty acid synthesis, urea cycle, and mitochondrial functions...
July 20, 2018: American Journal of Pathology
Aaron J Scott, John J Arcaroli, Stacey M Bagby, Rachel Yahn, Kendra M Huber, Natalie J Serkova, Anna Nguyen, Jihye Kim, Andrew Thorburn, Jon Vogel, Kevin S Quackenbush, Anna Capasso, Anna Schreiber, Patrick Blatchford, Peter J Klauck, Todd M Pitts, S Gail Eckhardt, Wells A Messersmith
Anti-angiogenic therapy used in treatment of metastatic colorectal cancer (mCRC) inevitably succumbs to treatment resistance. Upregulation of MET may play an essential role to acquired anti-VEGF resistance. We previously reported that cabozantinib (XL184), an inhibitor of receptor tyrosine kinases (RTKs) including MET, AXL, and VEGFR2, had potent antitumor effects in mCRC patient-derived tumor explant models. In this study, we examined the mechanisms of cabozantinib sensitivity, using regorafenib as a control...
July 19, 2018: Molecular Cancer Therapeutics
Peter P Ruvolo
Cancer cells depend on a supportive niche (the tumor microenvironment) that promotes tumor cell survival while protecting the malignant cells from therapeutic challenges and the host's defense systems. Cancer cells and the support cells in the tumor microenvironment communicate via cytokines/chemokines, cell:cell contact, or alterations in the metabolic state of the niche (e.g. hypoxia) that promote growth and survival of the tumor cell, influence metastasis, and defeat immune surveillance. These signaling pathways involve dysregulation of not only protein kinases but also protein phosphatases as normal signal transduction processes require both activation and deactivation...
July 17, 2018: Biochimica et Biophysica Acta
Alejandra Guerra-Castellano, Antonio Díaz-Quintana, Gonzalo Pérez-Mejías, Carlos A Elena-Real, Katiuska González-Arzola, Sofía M García-Mauriño, Miguel A De la Rosa, Irene Díaz-Moreno
Respiratory cytochrome c has been found to be phosphorylated at tyrosine 97 in the postischemic brain upon neuroprotective insulin treatment, but how such posttranslational modification affects mitochondrial metabolism is unclear. Here, we report the structural features and functional behavior of a phosphomimetic cytochrome c mutant, which was generated by site-specific incorporation at position 97 of p -carboxymethyl-l-phenylalanine using the evolved tRNA synthetase method. We found that the point mutation does not alter the overall folding and heme environment of cytochrome c , but significantly affects the entire oxidative phosphorylation process...
July 31, 2018: Proceedings of the National Academy of Sciences of the United States of America
Ming Tian, Xiaoyun Xu, Fengxia Liu, Xin Fan, Siyi Pan
Broccoli sprouts have attracted considerable attention because of their abundant phytochemicals and high selenium accumulation capacity, which reportedly reduce the risks of different cancers and cardiovascular diseases. In this study, an untargeted metabolomics approach was developed to investigate the effect of 5 days of treatment with 100 μmol/L selenate on the metabolome of broccoli sprouts. Results showed that the total sulfur content was slightly lower and the total selenium content was significantly higher in the selenate-treated sprouts...
September 2018: Food Research International
Vijaya L Damaraju, Michelle Kuzma, Carol E Cass, Charles T Putman, Michael B Sawyer
Tyrosine kinase inhibitors (TKIs) have advanced cancer treatment and prognosis but have also resulted in adverse effects such as fatigue, diarrhea, hypothyroidism, and other toxicities. We investigated TKI effects on skeletal muscle as a possible explanation of TKI induced fatigue. Changes in mitochondrial function due to inhibition of oxidative phosphorylation complexes, generation of superoxides, and inhibition of key transporters involved in uptake of glucose and/or nucleosides may result in alteration of energy metabolism and/or mitochondrial function...
July 2, 2018: Biochemical Pharmacology
Alexandra R Himel, Sharon A Cabral, James P Shaffery, Bernadette E Grayson
Surgical weight loss results in a host of metabolic changes that culminate in net positive health benefit to the patients. However, the psychological impact of these surgeries has not been fully studied. On one hand, surgical weight loss has been reported to improve standard quality of life and resolution of symptoms of depression. But on the other hand, reports of self-harm and increased ER visits for self-harm suggest other psychological difficulties. Inability to handle anxiety following surgical weight loss has alarming potential ramifications for these gastric surgery patients...
2018: PloS One
Seline van den Ameele, Dietmar Fuchs, Violette Coppens, Peter de Boer, Maarten Timmers, Bernard Sabbe, Manuel Morrens
Background: A mild pro-inflammatory status accompanies bipolar disorder (BD). Inflammation can cause a shift in monoamine metabolism, thereby activating more cytotoxic pathways. The extent to which low-grade inflammation in BD interacts with monoamine metabolism and how this accords to aging and clinical course is unknown. Objectives: We evaluated the presence of alterations in inflammation and monoamine metabolism in BD throughout different mood states and the role of aging therein. Methods: Sixty-seven patients with BD were included during an acute mood episode, either depressive ( n = 29), (hypo)manic ( n = 29), or mixed ( n = 9)...
2018: Frontiers in Psychiatry
Y Pi, K Gao, Y Peng, C L Mu, W Y Zhu
Gut microbes, especially those in the large intestine, are actively involved in nutrient metabolism; however, their impact on host nitrogen (N) metabolism remains largely unknown. This study was designed to investigate the effects of feeding a cocktail of antibiotics (AGM) (ampicillin, gentamycin and metronidazole) on intestinal microbiota, N utilization efficiency, and amino acid (AA) digestibility in cannulated pigs, with the aim of exploring the impact of gut microbiota on host N metabolism. In total, 16 piglets were surgically fitted with a simple distal ileal T-cannula and a jugular venous catheter...
June 29, 2018: Animal: An International Journal of Animal Bioscience
Manoj Nepal, Chi Ma, Guoxiang Xie, Wei Jia, Peiwen Fei
Given importance of 22-Fanconi Anemia (FA) proteins together to act in a signaling pathway in preventing deleterious clinical symptoms, e.g. severe bone marrow failure, congenital defects, an early onset of aging and cancer, studies on each FA protein become increasingly attractive. However, an unbiased and systematic investigation of cellular effects resulting from each FA protein is missing. Here, we report roles of FA complementation C group protein (FANCC) in the protection from metabolic disorders. This study was prompted by the diabetes-prone feature displayed in FANCC knockout mice, which is not typically shown in patients with FA...
June 21, 2018: Aging
João C P Silva, Marta Mota, Fátima O Martins, Célia Nogueira, Teresa Gonçalves, Tatiana Carneiro, Joana Pinto, Daniela Duarte, António S Barros, John G Jones, Ana M Gil
Increased sugar intake is implicated in Type-2 diabetes and fatty liver disease; however, the mechanisms through which glucose and fructose promote these conditions are unclear. We hypothesize that alterations in intestinal metabolite and microbiota profiles specific to each monosaccharide are involved. Two groups of six adult C57BL/6 mice were fed for 10-weeks with diets with glucose (G) or fructose (F) as sole carbohydrates, and a third group was fed with a normal chow carbohydrate mixture (N). Fecal metabolites were profiled by nuclear magnetic resonance (NMR) and microbial composition by real-time polymerase chain reaction (qPCR)...
August 3, 2018: Journal of Proteome Research
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