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Altered tyrosine metabolism

Wu Luo, Xiao-Mian Lin, Tian-Xiang Wang, Jia-Long Cai, Xiang-Feng Zeng, Cai-Rong Zhu, Rong-Zhen Li, Heng Wang, Xiao-Ping Wu
Previous studies suggest that specific binding to the complex consisting of fibroblast growth factor receptor-1 (FGFR1) and the coreceptor beta-Klotho (KLB) is the premise for human FGF19 and FGF21 activating the downstream signaling cascades, and regulating the metabolic homeostasis. However, it was found that human FGF21 loses its ability to bind to FGFR1-KLB after iodination with Na125 I and chloramine T, whereas human FGF19 retained its affinity for FGFR1-KLB even after iodination. The molecular mechanisms underlying these differences remained elusive...
October 14, 2018: Journal of Cellular Physiology
J Singh, M Cerghet, L M Poisson, I Datta, K Labuzek, H Suhail, R Rattan, Shailendra Giri
Identification of non-invasive biomarkers of disease progression in multiple sclerosis (MS) is critically needed for monitoring the disease progression and for effective therapeutic interventions. Urine is an attractive source for non-invasive biomarkers because it is easily obtained in the clinic. In search of a urine metabolite signature of progression in chronic experimental autoimmune encephalomyelitis (EAE), we profiled urine at the chronic stage of the disease (day 45 post immunization) by global untargeted metabolomics...
October 12, 2018: Journal of Neuroimmune Pharmacology: the Official Journal of the Society on NeuroImmune Pharmacology
K Cui, B Wang, T Ma, B W Si, N F Zhang, Y Tu, Q Y Diao
The present study aimed to investigate the compensatory effect of early protein restriction followed by a realimentation on growth performance of lamb and to explore the transcriptomic changes in liver. Thirty-two lambs with an initial birth weight of 2.3 ± 0.20 kg that were weaned on day 15 were randomly divided into two groups. The lambs were fed a basal diet with normal protein level (NPL, protein level in the milk replacer and starter, 25 and 21%, respectively) or low protein level (LPL, protein level in the milk replacer and starter, 19 and 15%, respectively) from 15 to 60 d, after which all lambs consumed the same diet with a normal protein level from 61 to 90 d...
October 12, 2018: Scientific Reports
Nathan G Lawler, Chris R Abbiss, Joel Pa Gummer, David I Broadhurst, Andrew D Govus, Timothy J Fairchild, Kevin G Thompson, Laura A Garvican-Lewis, Christopher J Gore, Garth L Maker, Robert D Trengove, Jeremiah J Peiffer
NEW FINDING: What is the central question of this study? To determine how 14 days of LHTL at simulated altitude alters an individual's metabolomic/metabolic profile? What is the main finding and its importance? This study demonstrated that ∼200 h of moderate simulated altitude exposure showed greater variance in measured metabolites between-person compared to within-person, which indicates individual variability during the adaptive phase to altitude exposure. In addition, metabolomics results indicate altitude alters multiple metabolic pathways of which the time course of these pathways is different over 14 days of altitude exposure...
October 12, 2018: Experimental Physiology
Cadence True, Anam Arik, Sarah Lindsley, Melissa Kirigiti, Elinor Sullivan, Paul Kievit
Maternal obesity and consumption of a high-fat diet (HFD) during pregnancy has a negative impact on offspring, including an increased risk for the development of obesity in adolescence. The mechanism for this transferred metabolic risk is unclear, but many studies have focused on the brain due to its important role in appetite and body-weight regulation. Two main pathways regulate appetite in the brain; homeostatic regulation that occurs predominantly in hypothalamic circuits and hedonic regulation of feeding that occurs via dopaminergic pathways...
2018: Frontiers in Endocrinology
Licia Grazzi, Alberto Raggi, Domenico D'Amico, Emanuela Sansone, Matilde Leonardi, Frank Andrasik, Antonina Gucciardi, Davide Guido, Giovanni D'Andrea
Aim To address whether, in patients with chronic migraine and medication overuse headache, mindfulness-based treatment is associated with changes in plasma levels of catecholamines and elusive amines that are similar to those observed in patients undergoing pharmacological prophylaxis. Methods In this non-randomized, clinic-based effectiveness study, patients aged 18-65, with a history of chronic migraine ≥ 10 years and overuse of triptans or non-steroidal anti-inflammatory drugs ≥ 5 years, were enrolled...
September 13, 2018: Cephalalgia: An International Journal of Headache
Cheng-Kun Tsai, Ta-Sen Yeh, Ren-Chin Wu, Ying-Chieh Lai, Meng-Han Chiang, Kuan-Ying Lu, Cheng-Yu Hung, Hung-Yao Ho, Mei-Ling Cheng, Gigin Lin
AIM: To explore the correlation of metabolomics profiles of gastric cancer (GC) with its chromosomal instability (CIN) status. METHODS: Nineteen GC patients were classified as CIN and non-CIN type by The Cancer Genome Atlas Research Group system, based on 409 oncogenes and tumor suppressor genes sequenced. The aqueous metabolites of the GC tumor and its surrounding adjacent healthy tissues were identified through liquid chromatography-mass spectrometry. Groups were compared by defining variable importance in projection score of > 1...
September 7, 2018: World Journal of Gastroenterology: WJG
Maria Apicella, Elisa Giannoni, Stephany Fiore, Karin Johanna Ferrari, Daniel Fernández-Pérez, Claudio Isella, Carlotta Granchi, Filippo Minutolo, Antonino Sottile, Paolo Maria Comoglio, Enzo Medico, Filippo Pietrantonio, Marco Volante, Diego Pasini, Paola Chiarugi, Silvia Giordano, Simona Corso
The microenvironment influences cancer drug response and sustains resistance to therapies targeting receptor-tyrosine kinases. However, if and how the tumor microenvironment can be altered during treatment, contributing to resistance onset, is not known. We show that, under prolonged treatment with tyrosine kinase inhibitors (TKIs), EGFR- or MET-addicted cancer cells displayed a metabolic shift toward increased glycolysis and lactate production. We identified secreted lactate as the key molecule instructing cancer-associated fibroblasts to produce hepatocyte growth factor (HGF) in a nuclear factor κB-dependent manner...
August 23, 2018: Cell Metabolism
Kiran Kurmi, Sadae Hitosugi, Jia Yu, Felix Boakye-Agyeman, Elizabeth K Wiese, Thomas R Larson, Qing Dai, Yuichi J Machida, Zhenkun Lou, Liewei Wang, Judy C Boughey, Scott H Kaufmann, Matthew P Goetz, Larry M Karnitz, Taro Hitosugi
How mitochondrial metabolism is altered by oncogenic tyrosine kinases to promote tumor growth is incompletely understood. Here, we show that oncogenic HER2 tyrosine kinase signaling induces phosphorylation of mitochondrial creatine kinase 1 (MtCK1) on tyrosine 153 (Y153) in an ABL-dependent manner in breast cancer cells. Y153 phosphorylation, which is commonly upregulated in HER2+ breast cancers, stabilizes MtCK1 to increase the phosphocreatine energy shuttle and promote proliferation. Inhibition of the phosphocreatine energy shuttle by MtCK1 knockdown or with the creatine analog cyclocreatine decreases proliferation of trastuzumab-sensitive and -resistant HER2+ cell lines in culture and in xenografts...
August 23, 2018: Cell 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...
November 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)...
November 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...
October 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
Antiangiogenic 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 (RTK) 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...
October 2018: Molecular Cancer Therapeutics
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