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phosphoproteomics, brain

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https://www.readbyqxmd.com/read/29064675/age-dependent-effects-of-acute-alcohol-administration-in-the-hippocampal-phosphoproteome
#1
Ana Contreras, Lidia Morales, Ali Tebourbi, Miguel Miguéns, Nuria Del Olmo, Carmen Pérez-García
Alcohol consumption during adolescence is deleterious to the developing brain and leads to persistent deficits in adulthood. Several results provide strong evidence for ethanol-associated alterations in glutamatergic signaling and impaired synaptic plasticity in the hippocampus. Protein phosphorylation is a well-known and well-documented mechanism in memory processes, but information on phosphoprotein alterations in hippocampus after ethanol exposure is limited. This study focuses on age-related changes in the hippocampal phosphoproteome after acute alcohol administration...
November 3, 2017: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/28879772/brain-membrane-proteome-and-phosphoproteome-reveal-molecular-basis-associating-with-nursing-and-foraging-behaviors-of-honeybee-workers
#2
Bin Han, Yu Fang, Mao Feng, Han Hu, Yue Hao, Chuan Ma, Xinmei Huo, Lifeng Meng, Xufeng Zhang, Fan Wu, Jianke Li
The brain is a vital organ in regulating complex social behaviors of honeybees including learning and memory. Knowledge of how brain membrane proteins and their phosphorylation underlie the age-related behavioral polyethism is still lacking. A hitherto age-resolved brain membrane proteome and phosphoproteome were reported in adult worker bees from two strains of honeybee (Apis mellifera ligustica): Italian bee (ITB) and Royal Jelly bee (RJB), a line selected from ITB for increased RJ outputs over four decades...
September 15, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28692454/phosphorylation-of-cyfip2-a-component-of-the-wave-regulatory-complex-regulates-dendritic-spine-density-and-neurite-outgrowth-in-cultured-hippocampal-neurons-potentially-by-affecting-the-complex-assembly
#3
Yeunkum Lee, Doyoun Kim, Jae Ryun Ryu, Yinhua Zhang, Shinhyun Kim, Yoonhee Kim, Bokyoung Lee, Woong Sun, Kihoon Han
Actin dynamics is a critical mechanism underlying many cellular processes in neurons. The heteropentameric WAVE-regulatory complex (WRC), consisting of WAVE, CYFIP1/2, Nap, Abi, and HSPC300, is a key regulator of actin dynamics that activates the Arp2/3 complex to initiate actin polymerization and branching. The WRC is basally inactive because of intermolecular interactions among the components, which can be modulated by bindings of phospholipids and Rac1, and phosphorylations of WAVE and Abi. However, the phosphorylation of other components of WRC and their functional significance remain largely unknown...
August 16, 2017: Neuroreport
https://www.readbyqxmd.com/read/28551015/salt-induced-phosphoproteomic-changes-in-the-hypothalamic-paraventricular-nucleus-in-rats-with-chronic-renal-failure
#4
Lanying Li, Jiawen Li, Lishan Tan, Minzi Qiu, Mengbi Zhang, Aiqing Li
Hypothalamic paraventricular nucleus (PVN) is a cardiovascular regulating center within the brain, which plays a critical role in high salt-induced progression of chronic renal failure (CRF). However, the phosphoproteomic changes in the PVN caused by CRF remain unclear. This study aimed to perform large-scale phosphoproteomic analysis of PVN induced by CRF and high salt intake. In this study, eight weeks post 5/6 nephrectomy (CRF model) or sham operation, Sprague-Dawley rats were fed a high-salt (4%) or normal-salt (0...
May 24, 2017: Brain Research
https://www.readbyqxmd.com/read/28512345/phosphoproteome-analysis-reveals-phosphorylation-underpinnings-in-the-brains-of-nurse-and-forager-honeybees-apis-mellifera
#5
Gebreamlak Bezabih, Han Cheng, Bin Han, Mao Feng, Yu Xue, Han Hu, Jianke Li
The honeybee brain is a central organ in regulating wide ranges of honeybee biology, including life transition from nurse to forager bees. Knowledge is still lacking on how protein phosphorylation governs the neural activity to drive the age-specific labor division. The cerebral phosphoproteome of nurse and forager honeybees was characterized using Ti(4+)-IMAC phosphopeptide enrichment mass-spectrometry-based proteomics and protein kinases (PKs) were predicted. There were 3,077 phosphosites residing on 3,234 phosphopeptides from 1004 phosphoproteins in the nurse bees...
May 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28508362/quantitative-phosphoproteomic-analysis-of-brain-tissues
#6
Bing Bai, Haiyan Tan, Junmin Peng
Protein phosphorylation regulates brain development and neuronal activities; and dysregulation of phosphorylation contributes to neurobiological disorders. Phosphoproteomic analysis provides comprehensive modification maps for measuring protein activities in cellular pathways and biological processes. Here, we introduce a mass spectrometry (MS)-based protocol to quantitatively analyze the phosphoproteome of human postmortem brains of Alzheimer's disease. In this isobaric labeling protocol, up to ten brain samples are selected from control and diseased cases for comparison...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28390667/pyridoxal-5-phosphate-mediated-preparation-of-immobilized-metal-affinity-material-for-highly-selective-and-sensitive-enrichment-of-phosphopeptides
#7
Qian Wang, Xiao-Mei He, Xi Chen, Gang-Tian Zhu, Ren-Qi Wang, Yu-Qi Feng
Phosphorylation is a crucial post-translational modification, which plays pivotal roles in various biological processes. Analysis of phosphopeptides by mass spectrometry (MS) is intractable on account of their low stoichiometry and the ion suppression from non-phosphopeptides. Thus, enrichment of phosphopeptides before MS analysis is indispensable. In this work, we employed pyridoxal 5'-phosphate (PLP), as an immobilized metal affinity chromatography (IMAC) ligand for the enrichment of phosphopeptides. PLP was grafted onto several substrates such as silica (SiO2), oxidized carbon nanotube (OCNT) and silica coated magnetic nanoparticles (Fe3O4@SiO2)...
May 26, 2017: Journal of Chromatography. A
https://www.readbyqxmd.com/read/28383256/phosphoproteomics-with-activated-ion-electron-transfer-dissociation
#8
Nicholas M Riley, Alexander S Hebert, Gerhard Dürnberger, Florian Stanek, Karl Mechtler, Michael S Westphall, Joshua J Coon
The ability to localize phosphosites to specific amino acid residues is crucial to translating phosphoproteomic data into biological meaningful contexts. In a companion manuscript ( Anal. Chem. 2017 , DOI: 10.1021/acs.analchem.7b00213 ), we described a new implementation of activated ion electron transfer dissociation (AI-ETD) on a quadrupole-Orbitrap-linear ion trap hybrid MS system (Orbitrap Fusion Lumos), which greatly improved peptide fragmentation and identification over ETD and other supplemental activation methods...
June 20, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28382306/apolipoprotein-e-mimetic-peptide-cn-105-improves-outcomes-in-ischemic-stroke
#9
Tian Ming Tu, Brad J Kolls, Erik J Soderblom, Viviana Cantillana, Paul Durham Ferrell, M Arthur Moseley, Haichen Wang, Hana N Dawson, Daniel T Laskowitz
OBJECTIVE: At present, the absence of a pharmacological neuroprotectant represents an important unmet clinical need in the treatment of ischemic and traumatic brain injury. Recent evidence suggests that administration of apolipoprotein E mimetic therapies represent a viable therapeutic strategy in this setting. We investigate the neuroprotective and anti-inflammatory properties of the apolipoprotein E mimetic pentapeptide, CN-105, in a microglial cell line and murine model of ischemic stroke...
April 2017: Annals of Clinical and Translational Neurology
https://www.readbyqxmd.com/read/28126228/phosphoproteome-of-crab-eating-macaque-cerebral-cortex-characterized-through-multidimensional-reversed-phase-liquid-chromatography-mass-spectrometry-with-tandem-anion-cation-exchange-columns
#10
Quan Quan, Jinwen Feng, Leong-Ting Lui, Tieliu Shi, Ivan K Chu
A fully automated online multidimensional liquid chromatography (MDLC) platform featuring high-/low-pH reversed-phase (RP) dimensions and two other complementary-strong anion exchange (SAX) and strong cation exchange (SCX), respectively-chromatographic separations in tandem, with conventional offline titanium dioxide pre-enrichment, has been applied for the first global phosphopeptide identification from the macaque cerebral cortex in the presence of phosphatase inhibitors. Phosphorylation data interpretation, including site determination, and network construction have been performed: 14,338 distinct phosphopeptides in 7572 non-redundant phosphosites at 1% FDR were identified with 784 novel phosphorylation sites when mapping into the two most-curated public phosphorylation databases, PhosphoSitePlus (PSP) and Phospho...
May 19, 2017: Journal of Chromatography. A
https://www.readbyqxmd.com/read/28112407/actin-filament-associated-protein-1-afap-1-is-a-key-mediator-in-inflammatory-signaling-induced-rapid-attenuation-of-intrinsic-p-gp-function-in-human-brain-capillary-endothelial-cells
#11
Yutaro Hoshi, Yasuo Uchida, Masanori Tachikawa, Sumio Ohtsuki, Tetsuya Terasaki
The purpose of this study was to identify regulatory molecule(s) involved in the inflammatory signaling-induced decrease in P-glycoprotein (P-gp) efflux function at the blood-brain barrier (BBB) that may occur in brain diseases. We confirmed that in vivo P-gp efflux activity at the BBB was decreased without any change in P-gp protein expression level in a mouse model of acute inflammation induced by 3 mg/kg lipopolysaccharide. In a human BBB model cell line (human brain capillary endothelial cells; hCMEC/D3), 1-h treatment with 10 ng/mL tumor necrosis factor-α (TNF-α; an inflammatory mediator) rapidly reduced P-gp efflux activity, but had no effect on P-gp protein expression level...
April 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/27834733/quantitative-proteomics-reveals-fundamental-regulatory-differences-in-oncogenic-hras-and-isocitrate-dehydrogenase-idh1-driven-astrocytoma
#12
Sophia Doll, Anatoly Urisman, Juan A Oses-Prieto, David Arnott, Alma L Burlingame
Glioblastoma multiformes (GBMs) are high-grade astrocytomas and the most common brain malignancies. Primary GBMs are often associated with disturbed RAS signaling, and expression of oncogenic HRAS results in a malignant phenotype in glioma cell lines. Secondary GBMs arise from lower-grade astrocytomas, have slower progression than primary tumors, and contain IDH1 mutations in over 70% of cases. Despite significant amount of accumulating genomic and transcriptomic data, the fundamental mechanistic differences of gliomagenesis in these two types of high-grade astrocytoma remain poorly understood...
January 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/27794539/human-r1441c-lrrk2-regulates-the-synaptic-vesicle-proteome-and-phosphoproteome-in-a-drosophila-model-of-parkinson-s-disease
#13
Md Shariful Islam, Hendrik Nolte, Wright Jacob, Anna B Ziegler, Stefanie Pütz, Yael Grosjean, Karolina Szczepanowska, Aleksandra Trifunovic, Thomas Braun, Hermann Heumann, Rolf Heumann, Bernhard Hovemann, Darren J Moore, Marcus Krüger
Mutations in leucine-rich repeat kinase 2 (LRRK2) cause late-onset, autosomal dominant familial Parkinson`s disease (PD) and variation at the LRRK2 locus contributes to the risk for idiopathic PD. LRRK2 can function as a protein kinase and mutations lead to increased kinase activity. To elucidate the pathophysiological mechanism of the R1441C mutation in the GTPase domain of LRRK2, we expressed human wild-type or R1441C LRRK2 in dopaminergic neurons of Drosophila and observe reduced locomotor activity, impaired survival and an age-dependent degeneration of dopaminergic neurons thereby creating a new PD-like model...
December 15, 2016: Human Molecular Genetics
https://www.readbyqxmd.com/read/27782176/functional-kinomics-establishes-a-critical-node-of-volume-sensitive-cation-cl-cotransporter-regulation-in-the-mammalian-brain
#14
Jinwei Zhang, Geng Gao, Gulnaz Begum, Jinhua Wang, Arjun R Khanna, Boris E Shmukler, Gerrit M Daubner, Paola de Los Heros, Paul Davies, Joby Varghese, Mohammad Iqbal H Bhuiyan, Jinjing Duan, Jin Zhang, Daniel Duran, Seth L Alper, Dandan Sun, Stephen J Elledge, Dario R Alessi, Kristopher T Kahle
Cell volume homeostasis requires the dynamically regulated transport of ions across the plasmalemma. While the ensemble of ion transport proteins involved in cell volume regulation is well established, the molecular coordinators of their activities remain poorly characterized. We utilized a functional kinomics approach including a kinome-wide siRNA-phosphoproteomic screen, a high-content kinase inhibitor screen, and a kinase trapping-Orbitrap mass spectroscopy screen to systematically identify essential kinase regulators of KCC3 Thr(991)/Thr(1048) phosphorylation - a key signaling event in cell swelling-induced regulatory volume decrease (RVD)...
October 26, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27752081/corticotropin-releasing-factor-overexpression-gives-rise-to-sex-differences-in-alzheimer-s-disease-related-signaling
#15
D A Bangasser, H Dong, J Carroll, Z Plona, H Ding, L Rodriguez, C McKennan, J G Csernansky, S H Seeholzer, R J Valentino
Several neuropsychiatric and neurodegenerative disorders share stress as a risk factor and are more prevalent in women than in men. Corticotropin-releasing factor (CRF) orchestrates the stress response, and excessive CRF is thought to contribute to the pathophysiology of these diseases. We previously found that the CRF1 receptor (CRF1) is sex biased whereby coupling to its GTP-binding protein, Gs, is greater in females, whereas β-arrestin-2 coupling is greater in males. This study used a phosphoproteomic approach in CRF-overexpressing (CRF-OE) mice to test the proof of principle that when CRF is in excess, sex-biased CRF1 coupling translates into divergent cell signaling that is expressed as different brain phosphoprotein profiles...
August 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/27748686/spinocerebellar-ataxia-type-12-clues-to-pathogenesis
#16
Rachael L Cohen, Russell L Margolis
PURPOSE OF REVIEW: Spinocerebellar ataxia type 12 (SCA12) is a rare autosomal dominant neurodegenerative disease characterized by tremor, gait abnormalities, and neuropsychiatric syndromes. The location of the causative CAG/CTG expansion mutation in PPP2R2B, a gene encoding regulatory units of the protein phosphatase 2A, may provide unique insights into the pathogenesis of neurodegeneration. RECENT FINDINGS: The first neuropathological examination of a brain from an SCA12 patient revealed both cerebellar and cerebral cortical atrophy, with a noted loss of Purkinje cells and no evidence of polyglutamine aggregates...
December 2016: Current Opinion in Neurology
https://www.readbyqxmd.com/read/27708245/chronic-low-dose-rate-ionising-radiation-affects-the-hippocampal-phosphoproteome-in-the-apoe-alzheimer-s-mouse-model
#17
Stefan J Kempf, Dirk Janik, Zarko Barjaktarovic, Ignacia Braga-Tanaka, Satoshi Tanaka, Frauke Neff, Anna Saran, Martin R Larsen, Soile Tapio
Accruing data indicate that radiation-induced consequences resemble pathologies of neurodegenerative diseases such as Alzheimer´s. The aim of this study was to elucidate the effect on hippocampus of chronic low-dose-rate radiation exposure (1 mGy/day or 20 mGy/day) given over 300 days with cumulative doses of 0.3 Gy and 6.0 Gy, respectively. ApoE deficient mutant C57Bl/6 mouse was used as an Alzheimer´s model. Using mass spectrometry, a marked alteration in the phosphoproteome was found at both dose rates...
November 1, 2016: Oncotarget
https://www.readbyqxmd.com/read/27703031/quantitative-phosphoproteomic-analysis-identifies-the-critical-role-of-jnk1-in-neuroinflammation-induced-by-japanese-encephalitis-virus
#18
Jing Ye, Hao Zhang, Wen He, Bibo Zhu, Dengyuan Zhou, Zheng Chen, Usama Ashraf, Yanming Wei, Ziduo Liu, Zhen F Fu, Huanchun Chen, Shengbo Cao
Japanese encephalitis virus (JEV) is the leading cause of epidemic encephalitis worldwide. The pathogenesis of JEV is linked to a robust inflammatory response in the central nervous system (CNS). Glial cells are the resident immune cells in the CNS and represent critical effectors of CNS inflammation. To obtain a global overview of signaling events in glial cells during JEV infection, we conducted phosphoproteomics profiling of a JEV-infected glial cell line. We identified 1816 phosphopeptides, corresponding to 1264 proteins, that exhibited a change in phosphorylation status upon JEV infection...
October 4, 2016: Science Signaling
https://www.readbyqxmd.com/read/27636850/comprehensive-quantitative-profiling-of-tau-and-phosphorylated-tau-peptides-in-cerebrospinal-fluid-by-mass-spectrometry-provides-new-biomarker-candidates
#19
Claire L Russell, Vikram Mitra, Karl Hansson, Kaj Blennow, Johan Gobom, Henrik Zetterberg, Mikko Hiltunen, Malcolm Ward, Ian Pike
Aberrant tau phosphorylation is a hallmark in Alzheimer's disease (AD), believed to promote formation of paired helical filaments, the main constituent of neurofibrillary tangles in the brain. While cerebrospinal fluid (CSF) levels of total tau and tau phosphorylated at threonine residue 181 (pThr181) are established core biomarkers for AD, the value of alternative phosphorylation sites, which may have more direct relevance to pathology, for early diagnosis is not yet known, largely due to their low levels in CSF and lack of standardized detection methods...
2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/27546785/phosphorylation-signals-in-striatal-medium-spiny-neurons
#20
REVIEW
Taku Nagai, Junichiro Yoshimoto, Takayuki Kannon, Keisuke Kuroda, Kozo Kaibuchi
Dopamine signaling in the brain is a complex phenomenon that strongly contributes to emotional behaviors. Medium spiny neurons (MSNs) play a major role in dopamine signaling through dopamine D1 receptors (D1Rs) or dopamine D2 receptors (D2Rs) in the striatum. cAMP/protein kinase A (PKA) regulates phosphorylation signals downstream of D1Rs, which affects the excitability of MSNs, leading to reward-associated emotional expression and memory formation. A combination of phosphoproteomic approaches and the curated KANPHOS database can be used to elucidate the physiological and pathophysiological functions of dopamine signaling and other monoamines...
October 2016: Trends in Pharmacological Sciences
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