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Shaoling Jiang, Hanchang He, Lishan Tan, Liangliang Wang, Zhengxiu Su, Yufeng Liu, Hongguo Zhu, Menghuan Zhang, Fan Fan Hou, Aiqing Li
Salt plays an essential role in the progression of chronic kidney disease and hypertension. However, the mechanisms underlying pathogenesis of salt-induced kidney damage remain largely unknown. Here, Sprague-Dawley rats, that underwent 5/6 nephrectomy (5/6Nx, a model of advanced kidney damage) or sham operation, were treated for 2 weeks with a normal or high-salt diet. We employed aTiO2 enrichment, iTRAQ labeling and liquid-chromatography tandem mass spectrometry strategy for proteomic and phosphoproteomic profiling of the renal cortex...
October 24, 2016: Scientific Reports
Chao Han, Shuke Nie, Guiqin Chen, Kai Ma, Nian Xiong, Zhentao Zhang, Yan Xu, Tao Wang, Stella M Papa, Xuebing Cao
Long-term L-DOPA treatment of Parkinson's disease is accompanied with fluctuations of motor responses and L-DOPA-induced dyskinesia (LID). Phosphorylation of the dopamine and c-AMP regulated phosphoprotein of 32 kDa (DARPP-32) plays a role in the pathogenesis of LID, and thus dephosphorylation of this protein by activated calcineurin may help reduce LID. One important activator of calcineurin is the Ca(2+) ionophore ionomycin. Here, we investigated whether intrastriatal injection of ionomycin to hemiparkinsonian rats produced changes in L-DOPA responses including LID...
October 19, 2016: Neuroscience
Susan Heavey, Sinead Cuffe, Stephen Finn, Vincent Young, Ronan Ryan, Siobhan Nicholson, Niamh Leonard, Niall McVeigh, Martin Barr, Kenneth O'Byrne, Kathy Gately
Clinical PI3K inhibition has been somewhat disappointing, due to both inadequate patient stratification and compensatory cell signalling through bypass mechanisms. As such, investigation of PI3K-MEK co-targeted inhibition has been recommended. With high mortality rates and a clear need for new therapeutic intervention strategies, non-small cell lung cancer (NSCLC) is an important setting to investigate the effectiveness of this approach.Here, 174 NSCLC tumours were screened for 150 mutations by Fluidigm technology, with 15 patients being profiled for phosphoprotein expression...
October 19, 2016: Oncotarget
Eva Liñeiro, Cristina Chiva, Jesús M Cantoral, Eduard Sabido, Francisco Javier Fernández-Acero
Phosphorylation is one of the main post-translational modification (PTM) involved in signaling network in the ascomycete Botrytis cinerea, one of the most relevant phytopathogenic fungus. The data presented in this article provided a differential mass spectrometry-based analysis of the phosphoproteome of B. cinerea under two different phenotypical conditions induced by the use of two different elicitors: glucose and deproteinized Tomate Cell Walls (TCW). A total 1138 and 733 phosphoproteins were identified for glucose and TCW culture conditions respectively...
June 2016: Data in Brief
Robert N Kirchdoerfer, Crystal L Moyer, Dafna M Abelson, Erica Ollmann Saphire
Filoviruses are capable of causing deadly hemorrhagic fevers. All nonsegmented negative-sense RNA-virus nucleocapsids are composed of a nucleoprotein (NP), a phosphoprotein (VP35) and a polymerase (L). However, the VP30 RNA-synthesis co-factor is unique to the filoviruses. The assembly, structure, and function of the filovirus RNA replication complex remain unclear. Here, we have characterized the interactions of Ebola, Sudan and Marburg virus VP30 with NP using in vitro biochemistry, structural biology and cell-based mini-replicon assays...
October 2016: PLoS Pathogens
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...
October 18, 2016: Molecular Psychiatry
Jasjeet Bhullar, Veena M Bhopale, Ming Yang, Kinjal Sethuraman, Stephen R Thom
This investigation explored the mechanism for microparticles (MPs) production by human and murine platelets exposed to high pressures of inert gases. Results demonstrate that MPs production occurs via an oxidative stress response in a dose-dependent manner and follows the potency series N2 > Ar > He. Gases with higher van der Waals volumes or polarizability such as SF6 and N2O, or hydrostatic pressure, do not cause MPs production. Singlet O2 is generated by N2, Ar and He, which is linked to NADPH oxidase (NOX) activity...
October 14, 2016: Free Radical Biology & Medicine
Guang-Yao Zhang, Yu-Hong Zhuang, Dan Shan, Guo-Fang Su, Serge Cosnier, Xueji Zhang
A simple and rapid photoelectrochemical (PEC) sensor is developed for the label-free detection of a phosphoprotein (α-casein) based on a zirconium based porphyrinic metal-organic framework (MOF), PCN-222, which exhibits an enhanced photocurrent response towards dopamine under the O2-saturated aqueous media. In this work, in terms of PEC measurements and cyclic voltammetry, the PEC behaviors of PCN-222 in aqueous media were thoroughly investigated for the first time. Additionally, in the virtue of the steric hindrance effect from the coordination of the phosphate groups and inorganic Zr-O clusters as binding sites in PCN-222, this biosensor shows high sensitivity for detecting α-casein and the limit of detection (LOD) is estimated to be 0...
October 18, 2016: Analytical Chemistry
Min Pang, Xin-Yan Bai, Yan Li, Ji-Zhong Bai, Li-Rong Yuan, Shou-An Ren, Xiao-Yun Hu, Xin-Ri Zhang, Bao-Feng Yu, Rui Guo, Hai-Long Wang
Clara cell protein (CC16) is an anti-inflammatory protein, which is expressed in the airway epithelium. It is involved in the development of airway inflammatory diseases, including chronic obstructive pulmonary disease and asthma. However, the exact molecular mechanism underlying its anti‑inflammatory action remains to be fully elucidated. The aim of the present study was to define the protein profiles of the anti‑inflammatory effect of CC16 in lipopolysaccharide (LPS)‑treated rat tracheal epithelial (RTE) cells using shotgun proteomics...
October 12, 2016: Molecular Medicine Reports
Lin-Lin Yuan, Ming Zhang, Xing Yan, Yan-Wei Bian, Shou-Min Zhen, Yue-Ming Yan
Drought stress is a major abiotic stress affecting plant growth and development. In this study, we performed the first dynamic phosphoproteome analysis of Brachypodium distachyon L. seedling leaves under drought stress for different times. A total of 4924 phosphopeptides, contained 6362 phosphosites belonging to 2748 phosphoproteins. Rigorous standards were imposed to screen 484 phosphorylation sites, representing 442 unique phosphoproteins. Comparative analyses revealed significant changes in phosphorylation levels at 0, 6, and 24 h under drought stress...
October 17, 2016: Scientific Reports
Anita Chopra, Sushant Soni, Haraprasad Pati, Dev Kumar, Rahul Diwedi, Deepak Verma, Garima Vishwakama, Sameer Bakhshi, Suman Kumar, Ajay Gogia, Rajive Kumar
BACKGROUND & OBJECTIVES: Mutation of nucleophosmin (NPM1) gene in the absence of FLT3-ITD (FMS related tyrosine kinase 3 - internal tandem duplications) mutation carries a good prognosis in cytogenetically normal acute myeloid leukaemia (AML). NPM1, a multifunctional nucleolar phosphoprotein that shuttles between nucleus and cytoplasm, gets trapped in the cytoplasm when mutated. Immunohistochemical (IHC) demonstration of its aberrant cytoplasmic location (NPMc+) has been suggested as a simple substitute for the standard screening molecular method...
June 2016: Indian Journal of Medical Research
A B Sudeep, Y K Gurav, V P Bondre
Chandipura virus (CHPV) (Vesiculovirus: Rhabdoviridae) garnered global attention as an emerging neurotropic pathogen inflicting high mortality in children within 24 h of commencement of symptoms. The 2003-2004 outbreaks in Central India witnessed case fatality rates ranging from 56-75 per cent in Andhra Pradesh and Gujarat with typical encephalitic symptoms. Due to the acute sickness and rapid deterioration, the precise mechanism of action of the virus is still unknown. Recent studies have shown increased expression of CHPV phosphoprotein upto 6 h post infection (PI) demonstrating CHPV replication in neuronal cells and the rapid destruction of the cells by apoptosis shed light on the probable mechanism of rapid death in children...
June 2016: Indian Journal of Medical Research
Marlen Thiere, Stefanie Kliche, Bettina Müller, Jan Teuber, Isabell Nold, Oliver Stork
Integrin-mediated cell adhesion and signaling is of critical importance for neuronal differentiation. Recent evidence suggests that an "inside-out" activation of β1-integrin, similar to that observed in hematopoietic cells, contributes to the growth and branching of dendrites. In this study, we investigated the role of the hematopoietic adaptor protein adhesion and degranulation promoting adapter protein (ADAP) in these processes. We demonstrate the expression of ADAP in the developing and adult nervous hippocampus, and in outgrowing dendrites of primary hippocampal neurons...
2016: Frontiers in Molecular Neuroscience
Jung-Hae Shin, Hyuk-Woo Kwon, Hyun-Jeong Cho, Man Hee Rhee, Hwa-Jin Park
BACKGROUND: Glycoprotein IIb/IIIa (αIIb/β3) is involved in platelet adhesion, and triggers a series of intracellular signaling cascades, leading to platelet shape change, granule secretion, and clot retraction. In this study, we evaluated the effect of ginsenoside Ro (G-Ro) on the binding of fibrinogen to αIIb/β3. METHODS: We investigated the effect of G-Ro on regulation of signaling molecules affecting the binding of fibrinogen to αIIb/β3, and its final reaction, clot retraction...
October 2016: Journal of Ginseng Research
Uros Kuzmanov, Hongbo Guo, Diana Buchsbaum, Jake Cosme, Cynthia Abbasi, Ruth Isserlin, Parveen Sharma, Anthony O Gramolini, Andrew Emili
Phospholamban (PLN) plays a central role in Ca(2+) homeostasis in cardiac myocytes through regulation of the sarco(endo)plasmic reticulum Ca(2+)-ATPase 2A (SERCA2A) Ca(2+) pump. An inherited mutation converting arginine residue 9 in PLN to cysteine (R9C) results in dilated cardiomyopathy (DCM) in humans and transgenic mice, but the downstream signaling defects leading to decompensation and heart failure are poorly understood. Here we used precision mass spectrometry to study the global phosphorylation dynamics of 1,887 cardiac phosphoproteins in early affected heart tissue in a transgenic R9C mouse model of DCM compared with wild-type littermates...
October 14, 2016: Proceedings of the National Academy of Sciences of the United States of America
Yan Zhou, Chenyan Zhao, Yabin Tian, Nan Xu, Youchun Wang
Hepatitis E virus (HEV) is a non-enveloped virus containing a single-stranded, positive-sense RNA genome of 7.2 kb, which consists of a 5' noncoding region, three open reading frames (ORFs), and a 3' noncoding region. ORF1 is diverse between genotypes and encodes the nonstructural proteins, which include the enzymes needed for virus replication. In addition to its role in virus replication, the function of ORF1 is relevant to viral adaption in cultured cells and may also relate to virus infection and HEV pathogenicity...
2016: Advances in Experimental Medicine and Biology
Koichiro Muromachi, Hiroshi Sugiya, Nobuyuki Tani-Ishii
In postnatal dentin formation, odontoblast differentiation occurs in the pulp tissue regenerative process under pathological condition. Odontoblasts and newly differentiated odontoblast-like cells beneath the caries lesion form tertiary dentin and are highly odontogenic. To observe the activity of dentinogenesis occur within the hard tissue, a combination of immunohistological analysis and immunodetection of dentinogenesis specific molecules, such as dentin sialophosphoprotein (DSPP) and/or its cleaved products dentin sialoprotein (DSP) and dentin phosphoprotein (DPP), is a reliable approach...
2017: Methods in Molecular Biology
Kai Chen, Fan Lv, Guofeng Xu, Min Zhang, Yeming Wu, Zhixiang Wu
Emerging evidence suggests receptor tyrosine kinase ALK as a promising therapeutic target in neuroblastoma. However, clinical trials reveal that a limited proportion of ALK-positive neuroblastoma patients experience clinical benefits from Crizotinib, a clinically approved specific inhibitor of ALK. The precise molecular mechanisms of aberrant ALK activity in neuroblastoma remain elusive, limiting the clinical application of ALK as a therapeutic target in neuroblastoma. Here, we describe a deep quantitative phosphoproteomic approach in which Crizotinib-treated neuroblastoma cell lines bearing aberrant ALK are used to investigate downstream regulated phosphoproteins...
October 7, 2016: Oncotarget
C M Wen, M M Chen, F H Nan, C S Wang
In this study, cultures of neural stem-progenitor cells (NSPC) from the brain of green terror cichlid Aequidens rivulatus were established and various NSPCs were demonstrated using immunocytochemistry. All of the NSPCs expressed brain lipid-binding protein, dopamine- and cAMP-regulated neuronal phosphoprotein 32 (DARPP-32), oligodendrocyte transcription factor 2, paired box 6 and sex determining region Y-box 2. The intensity and localisation of these proteins, however, varied among the different NSPCs. Despite being intermediate cells, NSPCs can be divided into radial glial cells, oligodendrocyte progenitor cells (OPC) and neuroblasts by expressing the astrocyte marker glial fibrillary acidic protein (GFAP), OPC marker A2B5 and neuronal markers, including acetyl-tubulin, βIII-tubulin, microtubule-associated protein 2 and neurofilament protein...
October 11, 2016: Journal of Fish Biology
Tamás Sticz, Anna Molnár, Ágnes Márk, Melinda Hajdu, Noémi Nagy, Gyula Végső, Tamás Micsik, László Kopper, Anna Sebestyén
AIMS: Tumour heterogeneity and altered activation of signalling pathways play important roles in therapy resistance. The PI3K/Akt/mTOR signalling network is a well-known regulator of several functions that contribute to tumour growth. mTOR exists in two functionally different multiprotein complexes. We aimed to determine mTOR activity-related proteins in clinically followed, conventionally treated colon carcinomas and to analyse the correlation between clinical data and mTORC1 and mTORC2 activity...
October 11, 2016: Journal of Clinical Pathology
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