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Glutamate Carboxypeptidase

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https://www.readbyqxmd.com/read/29196255/hypermethylation-of-pgcp-gene-is-associated-with-human-bronchial-epithelial-cells-immortalization
#1
Chen Gao, Xiumei Xing, Zhini He, Shen Chen, Shan Wang, Qingye Li, Ping Guo, Haiyan Zhang, Huiyao Li, Liping Chen, Qing Wang, Jian Zhao, Yongmei Xiao, Wen Chen, Daochuan Li
Cell immortalization is the initial step for cancer development. To identify the differentially expressed genes regulated by DNA methylation over the course of human primary bronchial epithelial cell (HPBECs) immortalization, an immortalized HBE cell line (HBETT) was generated via introduction of an SV40 LT and a catalytic subunit of human telomerase reverse transcriptase (hTERT) into the HPBECs. Microarrays of mRNA and DNA methylation were performed to compare the transcriptomes and DNA methylomes between these two types of cells...
November 28, 2017: Gene
https://www.readbyqxmd.com/read/29149993/label-free-determination-of-prostate-specific-membrane-antigen-in-human-whole-blood-at-nanomolar-levels-by-magnetically-assisted-surface-enhanced-raman-spectroscopy
#2
Zuzana Chaloupková, Anna Balzerová, Jitka Bařinková, Zdenka Medříková, Pavel Šácha, Petr Beneš, Václav Ranc, Jan Konvalinka, Radek Zbořil
Prostate cancer is one of the most common cancers among men and can in its later stages cause serious medical problems. Due to the limited suitability of current diagnostic biochemical markers, new biomarkers for the detection of prostate cancer are highly sought after. An ideal biomarker should serve as a reliable prognostic marker, be applicable for early diagnosis, and be applicable for monitoring of therapeutic response. One potential candidate is glutamate carboxypeptidase II (GCPII), also known as prostate specific membrane antigen (PSMA), which has a promising role for direct imaging...
January 2, 2018: Analytica Chimica Acta
https://www.readbyqxmd.com/read/29141866/prostate-specific-membrane-antigen-cleavage-of-vitamin-b9-stimulates-oncogenic-signaling-through-metabotropic-glutamate-receptors
#3
Charalambos Kaittanis, Chrysafis Andreou, Haley Hieronymus, Ninghui Mao, Catherine A Foss, Matthias Eiber, Gregor Weirich, Palak Panchal, Anuradha Gopalan, Juan Zurita, Samuel Achilefu, Gabriela Chiosis, Vladimir Ponomarev, Markus Schwaiger, Brett S Carver, Martin G Pomper, Jan Grimm
Prostate-specific membrane antigen (PSMA) or folate hydrolase 1 (FOLH1) is highly expressed on prostate cancer. Its expression correlates inversely with survival and increases with tumor grade. However, the biological role of PSMA has not been explored, and its role in prostate cancer remained elusive. Filling this gap, we demonstrate that in prostate cancer, PSMA initiates signaling upstream of PI3K through G protein-coupled receptors, specifically via the metabotropic glutamate receptor (mGluR). PSMA's carboxypeptidase activity releases glutamate from vitamin B9 and other glutamated substrates, which activate mGluR I...
November 15, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29020418/striatal-n-acetylaspartate-synthetase-shati-nat8l-regulates-depression-like-behaviors-via-mglur3-mediated-serotonergic-suppression-in-mice
#4
Yoshiaki Miyamoto, Noriyuki Iegaki, Kequan Fu, Yudai Ishikawa, Kazuyuki Sumi, Sota Azuma, Kyosuke Uno, Shin-Ichi Muramatsu, Atsumi Nitta
Background: Several clinical studies have suggested that N-acetylaspartate and N-acetylaspartylglutamate levels in the human brain are associated with various psychiatric disorders, including major depressive disorder. We have previously identified Shati/Nat8l, an N-acetyltransferase, in the brain using an animal model of psychosis. Shati/Nat8l synthesizes N-acetylaspartate from L-aspartate and acetyl-coenzyme A. Further, N-acetylaspartate is converted into N-acetylaspartylglutamate, a neurotransmitter for metabotropic glutamate receptor 3...
December 1, 2017: International Journal of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28904865/mouse-glutamate-carboxypeptidase%C3%A2-ii-gcpii-has-a-similar-enzyme-activity-and-inhibition-profile-but-a-different-tissue-distribution-to-human-gcpii
#5
Tomáš Knedlík, Barbora Vorlová, Václav Navrátil, Jan Tykvart, František Sedlák, Šimon Vaculín, Miloslav Franěk, Pavel Šácha, Jan Konvalinka
Glutamate carboxypeptidase II (GCPII), also known as prostate-specific membrane antigen (PSMA) or folate hydrolase, is a metallopeptidase expressed predominantly in the human brain and prostate. GCPII expression is considerably increased in prostate carcinoma, and the enzyme also participates in glutamate excitotoxicity in the brain. Therefore, GCPII represents an important diagnostic marker of prostate cancer progression and a putative target for the treatment of both prostate cancer and neuronal disorders associated with glutamate excitotoxicity...
September 2017: FEBS Open Bio
https://www.readbyqxmd.com/read/28763226/enhanced-brain-delivery-of-2-phosphonomethyl-pentanedioic-acid-following-intranasal-administration-of-its-%C3%AE-substituted-ester-prodrugs
#6
Michael Nedelcovych, Ranjeet P Dash, Lukáš Tenora, Sarah C Zimmermann, Alexandra J Gadiano, Caroline Garrett, Jesse Alt, Kristen R Hollinger, Elie Pommier, Andrej Jančařík, Camilo Rojas, Ajit G Thomas, Ying Wu, Krystyna Wozniak, Pavel Majer, Barbara S Slusher, Rana Rais
2-(Phosphonomethyl)pentanedioic acid (2-PMPA) is a potent and selective inhibitor of glutamate carboxypeptidase-II (GCPII) with efficacy in multiple neurological and psychiatric disease models, but its clinical utility is hampered by low brain penetration due to the inclusion of multiple acidic functionalities. We recently reported an improvement in the brain-to-plasma ratio of 2-PMPA after intranasal (IN) dosing in both rodents and primates. Herein, we describe the synthesis of several 2-PMPA prodrugs with further improved brain delivery of 2-PMPA after IN administration by masking of the γ-carboxylate...
October 2, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28759215/discovery-of-a-para-acetoxy-benzyl-ester-prodrug-of-a-hydroxamate-based-glutamate-carboxypeptidase-ii-inhibitor-as-oral-therapy-for-neuropathic-pain
#7
Rana Rais, Jan Vávra, Tomáš Tichý, Ranjeet P Dash, Alexandra J Gadiano, Lukáš Tenora, Lenka Monincová, Cyril Bařinka, Jesse Alt, Sarah C Zimmermann, C Ethan Slusher, Ying Wu, Krystyna Wozniak, Pavel Majer, Takashi Tsukamoto, Barbara S Slusher
4-Carboxy-α-[3-(hydroxyamino)-3-oxopropyl]-benzenepropanoic acid 1 is a potent hydroxamate-based inhibitor of glutamate carboxypeptidase II. In an attempt to improve its poor oral pharmacokinetics, we synthesized a series of prodrugs by masking its hydrophilic hydroxamate group. Prodrugs were evaluated for oral availability in mice and showed varying degree of plasma exposure to 1. Of these, para-acetoxybenzyl-based, 4-(5-(((4-acetoxybenzyl)oxy)amino)-2-carboxy-5-oxopentyl)benzoic acid, 12, provided 5-fold higher plasma levels of 1 compared to oral administration of 1 itself...
September 28, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28711565/new-aspects-of-molecular-imaging-in-prostate-cancer
#8
REVIEW
Francesco Ceci, Paolo Castellucci, Juliano J Cerci, Stefano Fanti
Nowadays several new imaging modalities are available for investigating prostate cancer (PCa) such as magnet resonance imaging (MRI) in the form of whole body MRI and pelvic multiparametric MRI and positron emission tomography (PET) using choline as radiotracers. Nevertheless, these modalities proved sub-optimal accuracy for detecting PCa metastases, particularly in the recurrence setting. A new molecular probe targeting the prostate specific membrane antigen (PSMA) has been recently developed for PET imaging...
November 1, 2017: Methods: a Companion to Methods in Enzymology
https://www.readbyqxmd.com/read/28701919/amyloid-%C3%AE-impairs-vesicular-secretion-in-neuronal-and-astrocyte-peptidergic-transmission
#9
Virginia Plá, Neus Barranco, Esther Pozas, Fernando Aguado
Regulated secretion of neuropeptides and neurotrophic factors critically modulates function and plasticity of synapses and circuitries. It is believed that rising amyloid-β (Aβ) concentrations, synaptic dysfunction and network disorganization underlie early phases of Alzheimer's disease (AD). Here, we analyze the impact of soluble Aβ1-42 assemblies on peptidergic secretion in cortical neurons and astrocytes. We show that neurons and astrocytes differentially produce and release carboxypeptidase E (CPE) and secretogranin III (SgIII), two dense-core vesicle (DCV) markers belonging to the regulated secretory pathway...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28326936/a-role-for-the-locus-coeruleus-in-the-analgesic-efficacy-of-n-acetylaspartylglutamate-peptidase-gcpii-inhibitors-zj43-and-2-pmpa
#10
Takahiro Nonaka, Toshihiko Yamada, Tatsuhiro Ishimura, Daiying Zuo, John R Moffett, Joseph H Neale, Tatsuo Yamamoto
N-acetylaspartylglutamate (NAAG) is the third most prevalent and widely distributed neurotransmitter in the mammalian nervous system. NAAG activates a group II metabotropic glutamate receptor (mGluR3) and is inactivated by an extracellular enzyme, glutamate carboxypeptidase II (GCPII) in vivo. Inhibitors of this enzyme are analgesic in animal models of inflammatory, neuropathic and bone cancer pain. NAAG and GCPII are present in the locus coeruleus, a center for the descending noradrenergic inhibitory pain system...
January 2017: Molecular Pain
https://www.readbyqxmd.com/read/28298410/fus-inclusions-disrupt-rna-localization-by-sequestering-kinesin-1-and-inhibiting-microtubule-detyrosination
#11
Kyota Yasuda, Sarah F Clatterbuck-Soper, Meredith E Jackrel, James Shorter, Stavroula Mili
Cytoplasmic inclusions of the RNA-binding protein fused in sarcoma (FUS) represent one type of membraneless ribonucleoprotein compartment. Formation of FUS inclusions is promoted by amyotrophic lateral sclerosis (ALS)-linked mutations, but the cellular functions affected upon inclusion formation are poorly defined. In this study, we find that FUS inclusions lead to the mislocalization of specific RNAs from fibroblast cell protrusions and neuronal axons. This is mediated by recruitment of kinesin-1 mRNA and protein within FUS inclusions, leading to a loss of detyrosinated glutamate (Glu)-microtubules (MTs; Glu-MTs) and an inability to support the localization of RNAs at protrusions...
April 3, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28285415/naag-peptidase-inhibitors-act-via-mglur3-animal-models-of-memory-alzheimer-s-and-ethanol-intoxication
#12
Rafal T Olszewski, Karolina J Janczura, Tomasz Bzdega, Elise K Der, Faustino Venzor, Brennen O'Rourke, Timothy J Hark, Kirsten E Craddock, Shankar Balasubramanian, Charbel Moussa, Joseph H Neale
Glutamate carboxypeptidase II (GCPII) inactivates the peptide neurotransmitter N-acetylaspartylglutamate (NAAG) following synaptic release. Inhibitors of GCPII increase extracellular NAAG levels and are efficacious in animal models of clinical disorders via NAAG activation of a group II metabotropic glutamate receptor. mGluR2 and mGluR3 knock-out (ko) mice were used to test the hypothesis that mGluR3 mediates the activity of GCPII inhibitors ZJ43 and 2-PMPA in animal models of memory and memory loss. Short- (1...
September 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28251297/glutamate-carboxypeptidase-ii-gcpii-inhibitor-2-pmpa-reduces-rewarding-effects-of-the-synthetic-cathinone-mdpv-in-rats-a-role-for-n-acetylaspartylglutamate-naag
#13
Callum Hicks, Ryan A Gregg, Sunil U Nayak, Lee Anne Cannella, Giana J Schena, Christopher S Tallarida, Allen B Reitz, Garry R Smith, Scott M Rawls
RATIONALE: Metabotropic glutamate 2 and 3 (mGluR2/3) receptors are implicated in drug addiction as they limit excessive glutamate release during relapse. N-acetylaspartylglutamate (NAAG) is an endogenous mGluR2/3 agonist that is inactivated by the glutamate carboxypeptidase II (GCPII) enzyme. GCPII inhibitors, and NAAG itself, attenuate cocaine-seeking behaviors. However, their effects on the synthetic cathinone 3,4-methylenedioxypyrovalerone (MDPV) have not been examined. OBJECTIVES: We determined whether withdrawal following repeated MDPV administration alters GCPII expression in corticolimbic regions...
June 2017: Psychopharmacology
https://www.readbyqxmd.com/read/28128286/role-of-cytosolic-carboxypeptidase-5-in-neuronal-survival-and-spermatogenesis
#14
Hui-Yuan Wu, Peng Wei, James I Morgan
Proteins may undergo a type of posttranslational modification - polyglutamylation, where a glutamate residue is enzymatically linked to the γ-carboxyl group of a glutamate in the primary sequence of proteins and additional glutamates are then sequentially added via α-carboxyl-linkages to the growing glutamate side chain. Nna1 (a.k.a. CCP1) defines the 6-member cytosolic carboxypeptidase (CCP) family that metabolizes polyglutamate side chain and its loss results in neurodegeneration and male infertility. Whereas most CCPs catalyze hydrolysis of α-carboxyl-linked glutamates, CCP5 uniquely metabolizes the γ-carboxyl linked, branch point glutamate...
January 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/27806330/plasma-glutamate-carboxypeptidase-is-a-negative-regulator-in-liver-cancer-metastasis
#15
Jae-Hye Lee, Hyun-Soo Cho, Jeong-Ju Lee, Soo Young Jun, Jun-Ho Ahn, Ju-Sik Min, Ji-Yong Yoon, Min-Hyuk Choi, Su-Jin Jeon, Jung Hwa Lim, Cho-Rok Jung, Dae-Soo Kim, Hyun-Taek Kim, Valentina M Factor, Yun-Han Lee, Snorri S Thorgeirsson, Cheol-Hee Kim, Nam-Soon Kim
Tumor metastasis is the leading cause of cancer death. In the metastatic process, EMT is a unique phenotypic change that plays an important role in cell invasion and changes in cell morphology. Despite the clinical significance, the mechanism underlying tumor metastasis is still poorly understood. Here we report a novel mechanism by which secreted plasma glutamate carboxypeptidase(PGCP) negatively involves Wnt/β-catenin signaling by DKK4 regulation in liver cancer metastasis. Pathway analysis of the RNA sequencing data showed that PGCP knockdown in liver cancer cell lines enriched the functions of cell migration, motility and mesenchymal cell differentiation...
November 29, 2016: Oncotarget
https://www.readbyqxmd.com/read/27743891/altered-meristem-program1-has-conflicting-effects-on-the-tolerance-to-heat-shock-and-symptom-development-after-pseudomonas-syringae-infection
#16
Min Woo Lee, Rira Seo, Yu Jeong Lee, Ju Hye Bae, Jung-Kwon Park, Joung-Hahn Yoon, Jei Wan Lee, Ho Won Jung
An Arabidopsis thaliana ALTERED MERISTEM PROGRAM1 (AtAMP1), which encodes a putative glutamate carboxypeptidase, not only controls shoot apical meristem development, but also is involved in tolerance response to abiotic stresses. Here, we introduce a novel mutant; named amp1-32 that is a phenocopier to previously isolated different amp1 mutant alleles. Interestingly, tiny leaves were continuously developed at the bottom of pre-emerged leaves in the amp1-32. The amp1-32 mutant was less sensitive to heat shock treatment lasting for 3 h, whereas disease symptoms were severely developed in the mutant after Pseudomonas syringae infection...
November 18, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27609368/evaluation-of-68ga-glutamate-carboxypeptidase-ii-ligand-positron-emission-tomography-for-clinical-molecular-imaging-of-atherosclerotic-plaque-neovascularization
#17
Thorsten Derlin, Johannes Thiele, Desiree Weiberg, James T Thackeray, Klaus Püschel, Hans-Jürgen Wester, Lukas Aguirre Dávila, Axel Larena-Avellaneda, Günter Daum, Frank M Bengel, Udo Schumacher
OBJECTIVE: Intraplaque neovascularization contributes to the progression and rupture of atherosclerotic lesions. Glutamate carboxypeptidase II (GCPII) is strongly expressed by endothelial cells of tumor neovasculature and plays a major role in hypoxia-induced neovascularization in rodent models of benign diseases. We hypothesized that GCPII expression may play a role in intraplaque neovascularization and may represent a target for imaging of atherosclerotic lesions. The aim of this study was to determine frequency, pattern, and clinical correlates of vessel wall uptake of a (68)Ga-GCPII ligand for positron emission tomographic imaging...
November 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/27536732/folh1-gcpii-is-elevated-in-ibd-patients-and-its-inhibition-ameliorates-murine-ibd-abnormalities
#18
Rana Rais, Weiwei Jiang, Huihong Zhai, Krystyna M Wozniak, Marigo Stathis, Kristen R Hollinger, Ajit G Thomas, Camilo Rojas, James J Vornov, Michael Marohn, Xuhang Li, Barbara S Slusher
Recent gene-profiling analyses showed significant upregulation of the folate hydrolase (FOLH1) gene in the affected intestinal mucosa of patients with inflammatory bowel disease (IBD). The FOLH1 gene encodes a type II transmembrane glycoprotein termed glutamate carboxypeptidase II (GCPII). To establish that the previously reported increased gene expression was functional, we quantified the glutamate carboxypeptidase enzymatic activity in 31 surgical specimens and report a robust 2.8- to 41-fold increase in enzymatic activity in the affected intestinal mucosa of IBD patients compared with an uninvolved area in the same patients or intestinal mucosa from healthy controls...
August 4, 2016: JCI Insight
https://www.readbyqxmd.com/read/27526115/the-therapeutic-and-diagnostic-potential-of-the-prostate-specific-membrane-antigen-glutamate-carboxypeptidase-ii-psma-gcpii-in-cancer-and-neurological-disease
#19
REVIEW
James C Evans, Meenakshi Malhotra, John F Cryan, Caitriona M O'Driscoll
Prostate specific membrane antigen (PSMA) otherwise known as glutamate carboxypeptidase II (GCPII) is a membrane bound protein that is highly expressed in prostate cancer and in the neovasculature of a wide variety of tumours including glioblastomas, breast and bladder cancers. This protein is also involved in a variety of neurological diseases including schizophrenia and ALS. In recent years, there has been a surge in the development of both diagnostics and therapeutics that take advantage of the expression and activity of PSMA/GCPII...
November 2016: British Journal of Pharmacology
https://www.readbyqxmd.com/read/27444540/blocking-glutamate-carboxypeptidase-ii-inhibits-glutamate-excitotoxicity-and-regulates-immune-responses-in-experimental-autoimmune-encephalomyelitis
#20
Danbee Ha, So Jin Bing, Ginnae Ahn, Jinhee Kim, Jinhee Cho, Areum Kim, Kalahe H I N M Herath, Hak Sun Yu, Sangmee Ahn Jo, Ik-Hyun Cho, Youngheun Jee
Experimental autoimmune encephalomyelitis (EAE) is an inflammatory disease in the murine central nervous system (CNS) and recapitulates the clinical and pathological features of human multiple sclerosis (MS). Glutamate carboxipeptidase II (GCPII), an enzyme expressed exclusively on astrocytes, is known to affect the disease progression of various neurological disorders by producing glutamate. Despite several findings indicating possible link between glutamate and MS/EAE, however, the involvement of astrocyte or GCPII on glutamate excitotoxicity has not received much attention in MS/EAE...
September 2016: FEBS Journal
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