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Altered tyrosine metabolism

Alessia Vignoli, Beatrice Orlandini, Leonardo Tenori, Maria Rosa Biagini, Stefano Milani, Daniela Renzi, Claudio Luchinat, Antonino Salvatore Calabrò
Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease characterized by ongoing inflammatory destruction of the interlobular bile ducts, eventually leading to chronic cholestasis and biliary cirrhosis. This study primarily aims to define the metabolomic signature of PBC after comparison with healthy controls (HC). Secondly it aims at evaluating the possible metabolic association between PBC and coeliac disease (CD), an immune-mediated disorder frequently associated with PBC. Serum and urine samples from 20 PBC, 21 CD and 19 sex-matched HC subjects were collected...
December 12, 2018: Journal of Proteome Research
Ying-Jian Song, Juan Tan, Xin-Huai Gao, Li-Xin Wang
Background: Lung cancer is one of the most common malignant tumors. Despite advances in lung cancer therapies, prognosis of non-small-cell lung cancer is still unfavorable. The aim of this study was to identify the prognostic value of key genes in lung tumorigenesis. Methods: Differentially expressed genes (DEGs) were screened out by GEO2R from three Gene Expression Omnibus cohorts. Common DEGs were selected for Kyoto Encyclopedia of Genes and Genomes pathway analysis and Gene Ontology enrichment analysis...
2018: Cancer Management and Research
Wuqun Tao, Jijing Tian, Tuan Xu, Li Xu, Heidi Qunhui Xie, Zhiguang Zhou, Zhiling Guo, Hualing Fu, Xuejiao Yin, Yangsheng Chen, Haiming Xu, Songyan Zhang, Wanglong Zhang, Chao Ma, Feng Ji, Jun Yang, Bin Zhao
Dechlorane 602 (Dec 602), a chlorinated flame retardant, has been widely detected in different environmental matrices and biota. However, toxicity data for Dec 602 seldom have been reported. A metabolomics study based on ultra-high performance liquid chromatography coupled with ion trap time-of-flight mass spectrometry was employed to study the urine and sera metabolic profiles of mice administered with Dec 602 (0, 0.001, 0.1, and 10 mg/kg body weight per day) for 7 days. A significant difference in metabolic profiling was observed between the Dec 602 treated group and the control group by multivariate analysis, which directly reflected the metabolic perturbations caused by Dec 602...
November 27, 2018: Environmental Pollution
Feng Zhang, Weijiang Zheng, Yongqiang Xue, Wen Yao
Unabsorbed copper accumulates in the hindgut of pigs that consume high levels of dietary copper, which enhances the coselection of antibiotic-resistant bacteria and is considered detrimental to the environment and to porcine health. In our study, a combination of 16S rRNA pyrosequencing and nontargeted metabolomics was used to investigate the microbiome-metabolome responses to dietary copper levels in the hindgut of suckling piglets. The results showed that the dietary copper level affected the abundance of several Clostridia genera and that the relative abundance of butyrate-producing bacteria, such as Coprococcus, Roseburia, and Acidaminococcus, was reduced in the 300 mg kg-1 (high) Cu group...
December 7, 2018: Applied Microbiology and Biotechnology
Yannan Fan, Sehrish K Bazai, Fabrice Daian, Maria Arechederra, Sylvie Richelme, Nuri A Temiz, Annie Yim, Bianca H Habermann, Rosanna Dono, David A Largaespada, Flavio Maina
BACKGROUND & AIMS: The variety of alterations found in hepatocellular carcinoma (HCC) challenges the identification of functionally relevant genes and their combinatorial actions in tumorigenesis. Deregulation of Receptor Tyrosine Kinases (RTKs) is frequent in HCC, yet little is known about the molecular events that cooperate with RTKs and whether these cooperative events play an active role at the root of liver tumorigenesis. METHODS: A forward genetic screen was performed using Sleeping Beauty transposon insertional mutagenesis to accelerate liver tumour formation in a genetic context in which subtly increased MET RTK levels predispose towards tumorigenesis...
December 5, 2018: Journal of Hepatology
Muhammad Shahid, Minyoung Lee, Honit Piplani, Allen M Andres, Bo Zhou, Austin Yeon, Minjung Kim, Hyung L Kim, Jayoung Kim
Prostate cancer (PC) is the most commonly diagnosed cancer in men and is the second leading cause of male cancer-related death in North America. Metabolic adaptations in malignant PC cells play a key role in fueling the growth and progression of the disease. Unfortunately, little is known regarding these changes in cellular metabolism. Here, we demonstrate that centromere protein F (CENPF), a protein associated with the centromere-kinetochore complex and chromosomal segregation during mitosis, is mechanically linked to altered metabolism and progression in PC...
December 9, 2018: Cell Cycle
Matheus C Bianchini, Claudia Ortiz Alves Gularte, Pablo A Nogara, Bárbara N Krum, Mateus C Gayer, Jessika C Bridi, Daniel H Roos, Rafael Roehrs, Roselei Fachinetto, Simone Pinton, Daiana S Ávila, Frank Hirth, João B T Rocha, Robson L Puntel
Thimerosal (THIM) is a well-established antifungal and antiseptic agent widely used as a preservative in vaccines. Recent studies identified the neurotoxic effects of THIM, including malfunction of the monoaminergic system. However, the underlying cytotoxic mechanisms are not well understood. Here we used the fruit fly Drosophila melanogaster to investigate the mechanisms of THIM-induced neurotoxicity. We focused on the dopaminergic system, and the rate-limiting enzyme tyrosine hydroxylase (DmTyrH), to test the hypothesis that THIM can impair dopamine (DA) homeostasis and subsequently cause dysfunction...
December 5, 2018: Metallomics: Integrated Biometal Science
Hongzhi Zhao, Han Li, Arthur Chi Kong Chung, Li Xiang, Xiaona Li, Yuanyuan Zheng, Hemi Luan, Lin Zhu, Wenyu Liu, Yang Peng, Yaxing Zhao, Shunqing Xu, Yuanyuan Li, Zongwei Cai
Despite the increasing research attention paid to gestational diabetes mellitus (GDM) due to its high prevalence, limited knowledge is available about its pathogenesis. In this study, 428 serum samples were collected from 107 pregnant women suffering GDM and 107 matched healthy controls. The non-targeted metabolomics data of maternal serum samples from the first (T1, n = 214) and second trimesters (T2, n = 214) were acquired by using ultra-high performance liquid chromatography coupled with Orbitrap mass spectrometry (MS)...
November 29, 2018: Journal of Proteome Research
You Yang, Guozhong Dong, Zhi Wang, Jian Wang, Zhu Zhang, Junhui Liu
High-grain diets are strongly associated with metabolic disorders in beef steers. Metabolomics can be used to explore the relationship between diet and metabolic changes, but no study has reported rumen and plasma metabolomics profiling associated with increasing dietary corn proportions in the diet of beef steers. Therefore, 12 steers paired according to similar body weights and body condition scores were randomly allocated to one of two diets: a low-corn (28.76%) diet (LCD) with a 40:60 ratio of concentrate to roughage and a high-corn (48...
2018: PloS One
Reyhaneh Farrokhi Yekta, Mostafa Rezaei Tavirani, Afsaneh Arefi Oskouie, Mohammad Reza Mohajeri-Tehrani, Ahmad Reza Soroush, Alireza Akbarzadeh Baghban
Objectives: As the most prevalent endocrine system malignancy, papillary thyroid carcinoma had a very fast rising incidence in recent years for unknown reasons besides the fact that the current methods in thyroid cancer diagnosis still hold some limitations. Therefore, the aim of this study was to improve the potential molecular markers for diagnosis of benign and malignant thyroid nodules to prevent unnecessary surgeries for benign tumors. Materials and Methods: In this study, 1H-NMR metabolomics platform was used to seek the discriminating serum metabolites in malignant papillary thyroid carcinoma (PTC) compared to benign multinodular goiter (MNG) and healthy subjects and also to better understand the disease mechanisms using bioinformatics analysis...
November 2018: Iranian Journal of Basic Medical Sciences
Judit Morello, Rico J E Derks, Susana S Lopes, Evelyne Steenvoorden, Emilia C Monteiro, Oleg A Mayboroda, Sofia A Pereira
Prevention and treatment of drug-induced renal injury (DIRI) rely on the availability of sensitive and specific biomarkers of early kidney injury and predictive animal models of human pathophysiology. This study aimed to evaluate the potential of zebrafish larvae as translational model in metabolic profiling of DIRI. Zebrafish larvae were exposed to the lethal concentration for 10% of the larvae (LC10) or ½ LC10 of gentamicin, paracetamol and tenofovir as tenofovir disoproxil fumarate (TDF) and tenofovir (TFV)...
2018: Frontiers in Pharmacology
Marcos V V de Oliveira, Xing Jin, Xuan Chen, Daniel Griffith, Sai Batchu, Hiroshi A Maeda
L-Tyrosine is an essential aromatic amino acid required for synthesis of proteins and a diverse array of plant natural products; however, little is known how the levels of tyrosine are controlled in planta and linked to overall growth and development. Most plants synthesize tyrosine by TyrA arogenate dehydrogenases, which are strongly feedback inhibited by tyrosine and encoded by TyrA1 and TyrA2 genes in Arabidopsis thaliana. While TyrA enzymes have been extensively characterized at biochemical levels, their in planta functions remain uncertain...
November 20, 2018: Plant Journal: for Cell and Molecular Biology
Mansi Shah, Ravi Bhatia
The majority of leukemia patients achieving remission ultimately relapse. Persistence of leukemia stem cells (LSC) capable of regenerating leukemia is a major cause of relapse. There is a pressing need to better understand mechanisms of LSC regulation and their resistance to therapy in order to improve outcomes for leukemia. Chronic myelogenous leukemia (CML) is a lethal myeloproliferative disorder that that is caused by hematopoietic stem cell (HSC) transformation by the BCR-ABL tyrosine kinase. Treatment with tyrosine kinase inhibitors (TKI) has revolutionized CML treatment, but fails to eliminate LSC responsible for propagating and regenerating leukemia...
2018: Advances in Experimental Medicine and Biology
Tássia B B C Costa, Acioly L T Lacerda, Caroline Dal Mas, Elisa Brietzke, João G M Pontes, Lucas A N Marins, Lucas G Martins, Marcel V Nunes, Mariana Pedrini, Michelle S C Carvalho, Milan P Mitrovitch, Mirian A F Hayashi, Natália L Saldanha, Ronei J Poppi, Ljubica Tasic
Approximately 255 million people consume illicit drugs every year, among which 18 million use cocaine. A portion of this drug is represented by crack, but it is difficult to estimate the number of users since most are marginalized. However, there are no recognized efficacious pharmacotherapies for crack-cocaine dependence. Inflammation and infection in cocaine users may be due to behavior adopted in conjunction with drug-related changes in the brain. To understand the metabolic changes associated with the drug abuse disorder and identify biomarkers, we performed a 1 H NMR-based metabonomic analysis of 44 crack users' and 44 healthy volunteers' blood serum...
November 12, 2018: Journal of Proteome Research
Mahsa Darbandi, Sara Darbandi, Ashok Agarwal, Saradha Baskaran, Sulagna Dutta, Pallav Sengupta, Hamid Reza Khorram Khorshid, Sandro Esteves, Kambiz Gilany, Mehdi Hedayati, Fatemeh Nobakht, Mohammad Mehdi Akhondi, Niknam Lakpour, Mohammad Reza Sadeghi
PURPOSE: This study was conducted in order to investigate the effects of reactive oxygen species (ROS) levels on the seminal plasma (SP) metabolite milieu and sperm dysfunction. METHODS: Semen specimens of 151 normozoospermic men were analyzed for ROS by chemiluminescence and classified according to seminal ROS levels [in relative light units (RLU)/s/106 sperm]: group 1 (n = 39): low (ROS < 20), group 2 (n = 38): mild (20 ≤ ROS < 40), group 3 (n = 31): moderate (40 ≤ ROS < 60), and group 4 (n = 43): high (ROS ≥ 60)...
October 31, 2018: Journal of Assisted Reproduction and Genetics
Pablo Bascuñana, Mirjam Brackhan, Ina Leiter, Heike Keller, Ina Jahreis, Tobias L Ross, Frank M Bengel, Marion Bankstahl, Jens P Bankstahl
Alterations in metabolism during epileptogenesis may be a therapy target. Recently, an increase in amino acid transport into the brain was proposed to play a role in epileptogenesis. We aimed to characterize alterations of substrate utilization during epileptogenesis and in chronic epilepsy. The lithium-pilocarpine post status epilepticus (SE) rat model was used. We performed longitudinal O-(2-[(18)F]fluoroethyl)-l-tyrosine (18 F-FET) and 18 F-fluorodeoxyglucose (18 F-FDG) positron emission tomography (PET) and calculated 18 F-FET volume of distribution (Vt ) and 18 F-FDG uptake...
October 30, 2018: Journal of Cerebral Blood Flow and Metabolism
Ting-Ting Mo, Hua Dai, Hang Du, Rui-Yuan Zhang, Ke-Ping Chai, Yao An, Ji-Ji Chen, Jun-Ke Wang, Zi-Jin Chen, Cheng-Zhi Chen, Xue-Jun Jiang, Rong Tang, Li-Ping Wang, Qiang Tan, Ping Tang, Xin-Yu Miao, Pan Meng, Long-Bin Zhang, Shu-Qun Cheng, Bin Peng, Bai-Jie Tu, Ting-Li Han, Yin-Yin Xia, Philip N Baker
Intake of arsenic (As) via drinking water has been a serious threat to global public health. Though there are numerous reports of As neurotoxicity, its pathogenesis mechanisms remain vague especially its chronic effects on metabolic network. Hippocampus is a renowned area in relation to learning and memory, whilst recently, cerebellum is argued to be involved with process of cognition. Therefore, the study aimed to explore metabolomics alternations in these two areas after chronic As exposure, with the purpose of further illustrating details of As neurotoxicity...
October 29, 2018: Environmental Toxicology
Steven Vetel, Sophie Sérrière, Johnny Vercouillie, Jackie Vergote, Gabrielle Chicheri, Jean-Bernard Deloye, Frédéric Dollé, Sylvie Bodard, Claire Tronel, Lydie Nadal-Desbarats, Antoine Lefèvre, Patrick Emond, Sylvie Chalon
Parkinson's disease (PD) is characterized by the degeneration of dopaminergic (DA) neurons constituting the nigrostriatal pathway. Neuroinflammation, related to microglial activation, plays an important role in this process. Exploration of animal models of PD using neuroimaging modalities allows to better understand the pathophysiology of the disease. Here, we fully explored a moderate lesion model in the rat in which 6-hydroxydopamine was unilaterally delivered in three sites along the striatum. The degenerative process was assessed through in vivo Positron Emission Tomography (PET) imaging and in vitro autoradiographic quantitation of the striatal dopamine transporter (DAT) and immunostaining of tyrosine hydroxylase (TH)...
October 28, 2018: Synapse
Eric Dietel, Alexander Brobeil, Stefan Gattenlöhner, Monika Wimmer
The protein tyrosine phosphatase interacting protein 51 (PTPIP51) regulates and interconnects signaling pathways, such as the mitogen-activated protein kinase (MAPK) pathway and an abundance of different others, e.g., Akt signaling, NF-κB signaling, and the communication between different cell organelles. PTPIP51 acts as a scaffold protein for signaling proteins, e.g., Raf-1, epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (Her2), as well as for other scaffold proteins, e...
October 22, 2018: International Journal of Molecular Sciences
Eliano Dos Santos, Joana F Sacramento, Bernardete F Melo, Sílvia V Conde
The carotid body (CB) is organized in clusters of lobules containing type I cells and type II cells, in a ratio of approximately 4:1. The CB undergoes structural and functional changes during perinatal development, in response to a variety of environmental stimuli and in pathological conditions. Knowing that the CB acts as a metabolic sensor involved in the control of peripheral insulin sensitivity and that its overactivation contributes to the genesis of metabolic disturbances, herein we tested if diet-induced insulin resistance is associated with morphological alterations in the proportion of type I and type II cells in the CB...
2018: Advances in Experimental Medicine and Biology
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