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He Dongsheng, Zhang Zhuo, Lao Jiamin, Meng Hailan, Han Lijuan, Chen Fan, Ye Dan, Zhang He, Xu Yun
Among various therapeutic approaches for stroke, treatment with human umbilical cord mesenchymal stem cells (hUC-MSCs) has acquired some promising results. However, the underlying mechanisms remain unclear. We analyzed the protein expression spectrum of the cortical peri-infarction region after ischemic stroke followed by treatment with hUC-MSCs, and found 16 proteins expressed differentially between groups treated with or without hUC-MSCs. These proteins were further determined by Gene Ontology term analysis and network with CD200-CD200R1, CCL21-CXCR3 and transcription factors...
October 2016: Aging and Disease
Hua Lin, Weiguo Sui, Wuxian Li, Qiupei Tan, Jiejing Chen, Xiuhua Lin, Hui Guo, Minglin Ou, Wen Xue, Ruohan Zhang, Yong Dai
Down syndrome (DS) is caused by trisomy of human chromosome 21 and is associated with a number of deleterious phenotypes. To investigate the role of microRNA (miRNA) in the regulation of DS, high‑throughput Illumina sequencing technology and isobaric tagging for relative and absolute protein quantification analysis were utilized for simultaneous expression profiling of miRNA and protein in fetuses with DS and normal fetuses. A total of 344 miRNAs were associated with DS. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses were used to investigate the proteins found to be differentially expressed...
September 26, 2016: Molecular Medicine Reports
Matthew Dean, Adam Lassak, Anna Wilk, Adriana Zapata, Luis Marrero, Patricia Molina, Krzysztof Reiss
Ethanol plays a detrimental role in the development of the brain. Multiple studies have shown that ethanol inhibits insulin-like growth factor I receptor (IGF-IR) function. Because the IGF-IR contributes to brain development by supporting neural growth, survival, and differentiation, we sought to determine the molecular mechanism(s) involved in ethanol's effects on this membrane-associated tyrosine kinase. Using multiple neuronal cell types, we performed Western blot, immunoprecipitation, and GST-pulldowns following acute (1 - 24 hours) or chronic (3 weeks) treatment with ethanol...
September 8, 2016: Journal of Cellular Physiology
Kang Li, Luobu Gesang, Zeng Dan, Lamu Gusang
The molecular mechanisms for hypoxic environment causing the injury of intestinal mucosal barrier (IMB) are widely unknown. To address the issue, Han Chinese from 100 m altitude and Tibetans from high altitude (more than 3650 m) were recruited. Histological and transcriptome analyses were performed. The results showed intestinal villi were reduced and appeared irregular, and glandular epithelium was destroyed in the IMB of Tibetans when compared with Han Chinese. Transcriptome analysis revealed 2573 genes with altered expression...
2016: Oxidative Medicine and Cellular Longevity
Ting-Ting Wang, Chan Tian, Jing Sun, Hui Wang, Bao-Yun Zhang, Cao Chen, Jing Wang, Kang Xiao, Li-Na Chen, Yan Lv, Chen Gao, Qi Shi, Yan Xin, Xiao-Ping Dong
Prion is a unique nucleic acid-free pathogen that causes human and animal fatal neurodegenerative diseases. Brain-derived neurotrophic factor (BDNF) is a prototypic neurotrophin that helps to support the survival of existing neurons, and encourage the growth and differentiation of new neurons and synapses through axonal and dendritic sprouting. There are two distinct classes of glycosylated receptors, neurotrophin receptor p75 (p75NTR) and tropomyosin-related kinase (Trk), that can bind to BDNF. To obtain insights into the possible alterations of brain BDNF and its signaling pathway in prion disease, the levels of BDNF and several molecules in the BDNF pathway in the brain tissues of scrapie agents 263K-infected hamsters were separately evaluated...
October 2016: International Journal of Biochemistry & Cell Biology
Shounak Baksi, Sangram Bagh, Sandip Sarkar, Debashis Mukhopadhyay
Aggregation prone Huntingtin (Htt) protein and its aberrations, causing protein misfolding, have been the prototype of intense research for several decades. Misfolded aggregates or oligomers of different sizes not only deregulate the homeostasis, cellular machinery also counterbalances the effects at least at the initial stages, till the balance tilts towards toxicity and degeneration. In this paper, we combine experimental approaches with system based computational modeling to decipher the molecular mechanisms as well as the hidden dynamics leading to neuronal death in HD...
August 30, 2016: Bio Systems
Birgit Manno, Thomas Oellerich, Tim Schnyder, Jasmin Corso, Marion Lösing, Konstantin Neumann, Henning Urlaub, Facundo D Batista, Michael Engelke, Jürgen Wienands
The SH2 domain-containing inositol 5'-phosphatase (SHIP) plays a key role in preventing autoimmune phenomena by limiting antigen-mediated B cell activation. SHIP function is thought to require the dual engagement of the BCR and negative regulatory coreceptors as only the latter appear capable of recruiting SHIP from the cytosol to the plasma membrane by virtue of phosphorylated immunoreceptor tyrosine-based inhibitory motifs. Here we demonstrate a coreceptor-independent membrane recruitment and function of SHIP in B cells...
August 23, 2016: European Journal of Immunology
Ulrike Strunk, Daniel Gomez Ramos, Holly A Saffran, James R Smiley
The abundant HSV-1 tegument protein VP11/12 encoded by gene UL46 is essential for induction of the PI3K/Akt-signaling pathway during infection. VP11/12 utilizes tyrosine-based motifs within its C-terminal region to bind the SH2 domains of Src family kinases, the p85 subunit of PI3 Kinase and Grb2, and the PTB domain of Shc. We previously proposed that the interaction with SFKs and p85 is used to gain control over the PI3K/Akt signaling pathway. We tested this model by evaluating the effects of mutations that eliminate each of these interactions on the ability of HSV-1 to activate Akt...
November 2016: Virology
Ismini Lasithiotaki, Eliza Tsitoura, Anastasios Koutsopoulos, Eleni Lagoudaki, Chara Koutoulaki, George Pitsidianakis, Demetrios A Spandidos, Nikolaos M Siafakas, George Sourvinos, Katerina M Antoniou
Merkel Cell Polyoma Virus (MCPyV) infection has been associated with non-small cell lung cancer (NSCLC). Viruses can manipulate cellular miRNAs or have a profound impact on cellular miRNA expression to control host regulatory pathways. In this study, we evaluated the expression profiles of cancer-associated and virally affected host microRNAs miR-21, miR-145, miR-146a, miR-155, miR-302c, miR-367 and miR-376c in a series of NSCLC tissue samples as well as in samples from "healthy" sites, distant from the tumour region that were either positive or negative for MCPyV DNA...
August 11, 2016: Oncotarget
Ling Liu, Yu Wei Phua, Rachel S Lee, Xiuquan Ma, Yiping Jenkins, Karel Novy, Emily S Humphrey, Howard Chan, Robert Shearer, Poh Chee Ong, Weiwen Dai, Darren N Saunders, Isabelle S Lucet, Roger J Daly
SgK269/PEAK1 is a pseudokinase and scaffolding protein that plays a critical role in regulating growth factor receptor signal output and is implicated in the progression of several cancers, including those of the breast, colon and pancreas. SgK269 is structurally related to SgK223, a human pseudokinase that also functions as a scaffold, but recruits a distinct repertoire of signaling proteins compared to SgK269. Structural similarities between SgK269 and SgK223 include a predicted α-helical region (designated CH) immediately preceding the conserved C-terminal pseudokinase (PK) domain...
August 16, 2016: Journal of Biological Chemistry
Sune M Christensen, Hsiung-Lin Tu, Jesse E Jun, Steven Alvarez, Meredith G Triplet, Jeffrey S Iwig, Kamlesh K Yadav, Dafna Bar-Sagi, Jeroen P Roose, Jay T Groves
SOS is a key activator of the small GTPase Ras. In cells, SOS-Ras signaling is thought to be initiated predominantly by membrane recruitment of SOS via the adaptor Grb2 and balanced by rapidly reversible Grb2-SOS binding kinetics. However, SOS has multiple protein and lipid interactions that provide linkage to the membrane. In reconstituted-membrane experiments, these Grb2-independent interactions were sufficient to retain human SOS on the membrane for many minutes, during which a single SOS molecule could processively activate thousands of Ras molecules...
September 2016: Nature Structural & Molecular Biology
Amir Hossein Massoud, Louis-Marie Charbonnier, David Lopez, Matteo Pellegrini, Wanda Phipatanakul, Talal A Chatila
Mechanisms by which regulatory T (Treg) cells fail to control inflammation in asthma remain poorly understood. We show that a severe asthma-associated polymorphism in the gene encoding the interleukin (IL)-4 receptor alpha chain (Il4ra(R576)) promotes conversion of induced Treg (iTreg) cells toward a T helper 17 (TH17) cell fate. This skewing is mediated by the recruitment by IL-4Rα(R576) of the growth-factor-receptor-bound protein 2 (GRB2) adaptor protein, which drives IL-17 expression by activating a pathway that involves extracellular-signal-regulated kinase, IL-6 and the transcription factor STAT3...
September 2016: Nature Medicine
Minakshi Nihal, Gary S Wood
Melanoma is one of the most aggressive and lethal forms of skin cancer. Despite recent improvements in targeted therapies, many patients with advanced disease fail to achieve lasting tumor regression. Therefore, it is important to develop novel druggable targets that can be exploited to improve clinical outcome. Here, we studied the role of Casitas B-lineage lymphoma (c-CBL), an E3 ubiquitin ligase, in human melanoma. Employing quantitative real-time PCR and Western blot analysis in a panel of human melanoma cell lines (A375, G361, Hs-294T, SK-Mel-2, SK-Mel-28 and 451Lu), we found that c-CBL is strongly expressed in human melanoma cells at the mRNA and protein levels...
July 27, 2016: Oncotarget
Robert B Quast, Andrei Sonnabend, Marlitt Stech, Doreen A Wüstenhagen, Stefan Kubick
Cell-free protein synthesis systems derived from eukaryotic sources often provide comparatively low amounts of several μg per ml of de novo synthesized membrane protein. In order to overcome this, we herein demonstrate the high-yield cell-free synthesis of the human EGFR in a microsome-containing system derived from cultured Sf21 cells. Yields were increased more than 100-fold to more than 285 μg/ml by combination of IRES-mediated protein translation with a continuous exchange cell-free reaction format that allowed for prolonged reaction lifetimes exceeding 24 hours...
2016: Scientific Reports
Maria I Toki, Daniel E Carvajal-Hausdorf, Mehmet Altan, Joseph McLaughlin, Brian Henick, Kurt Schalper, Konstantinos N Syrigos, David L Rimm
INTRODUCTION: Epidermal Growth Factor Receptor (EGFR) is a therapeutic target in Non-Small Cell Lung Cancer (NSCLC) for EGFR mutant patients. Proximity ligation assay (PLA) is a method to detect functional signaling associated protein complexes. GRB2 is an adaptor protein which binds to the phosphorylated residues of active EGFR. EGFR and GRB2 interaction, correlates with active EGFR signaling and leads to activation of MAPK/ERK pathway. METHODS: A PLA developed to detect EGFR:GRB2 interaction was measured by quantitative immunofluorescence (QIF) using AQUA(®) technology...
July 19, 2016: Journal of Thoracic Oncology
Chih-Feng Chian, Yi-Ting Hwang, Harn-Jing Terng, Shih-Chun Lee, Tsui-Yi Chao, Hung Chang, Ching-Liang Ho, Yi-Ying Wu, Wann-Cherng Perng
Peripheral blood mononuclear cell (PBMC)-derived gene signatures were investigated for their potential use in the early detection of non-small cell lung cancer (NSCLC). In our study, 187 patients with NSCLC and 310 age- and gender-matched controls, and an independent set containing 29 patients for validation were included. Eight significant NSCLC-associated genes were identified, including DUSP6, EIF2S3, GRB2, MDM2, NF1, POLDIP2, RNF4, and WEE1. The logistic model containing these significant markers was able to distinguish subjects with NSCLC from controls with an excellent performance, 80...
July 13, 2016: Oncotarget
Parinaz Kazemi, Mojtaba Dashtizad, Mehdi Shamsara, Forough Mahdavinezhad, Ehsan Hashemi, Samaneh Fayazi, Hadi Hajarian
Artificial collapse of the blastocoel cavity before vitrification can improve the quality of warmed embryos, yet how reduction of blastocoel fluid impacts formation of the blastocyst cell lineages is not clear. The present study assessed the effect of pre-vitrification blastocoel fluid reduction on the survival, hatching rate, and the expression of genes related to apoptosis (Tp53), pluripotency (Pou5f1, Nanog), and differentiation (Cdx2, Eomes, Gata6) in mouse blastocysts. In vivo-produced blastocysts were randomly divided into three groups: The first group was vitrified and warmed; the second group underwent artificial collapse of the blastocoel cavity prior to vitrification and warming; the third group served as the control, in which neither vitrification or artificial collapse was performed...
August 2016: Molecular Reproduction and Development
Masakiyo Sakaguchi, Mami Yamamoto, Masashi Miyai, Tatsuo Maeda, Junichiro Hiruma, Hitoshi Murata, Rie Kinoshita, I Made Winarsa Ruma, Endy Widya Putranto, Yusuke Inoue, Shin Morizane, Nam-Ho Huh, Ryoji Tsuboi, Toshihiko Hibino
We previously reported a positive feedback loop between S100A8/A9 and pro-inflammatory cytokines mediated by extracellular matrix metalloproteinase inducer (EMMPRIN), an S100A9 receptor. Here, we identify neuroplastin-β (NPTNβ) as an unreported S100A8 receptor. NPTNβ and EMMPRIN form homodimers and a heterodimer, and are co-localized on the surface of cultured normal human keratinocytes (NHK). Knockdown of both receptors suppressed cell proliferation and pro-inflammatory cytokine induction. Upon stimulation with S100A8, NPTNβ recruited Grb2 and activated ERK, resulting in keratinocyte proliferation...
July 4, 2016: Journal of Investigative Dermatology
William Y C Huang, Qingrong Yan, Wan-Chen Lin, Jean K Chung, Scott D Hansen, Sune M Christensen, Hsiung-Lin Tu, John Kuriyan, Jay T Groves
The assembly of cell surface receptors with downstream signaling molecules is a commonly occurring theme in multiple signaling systems. However, little is known about how these assemblies modulate reaction kinetics and the ultimate propagation of signals. Here, we reconstitute phosphotyrosine-mediated assembly of extended linker for the activation of T cells (LAT):growth factor receptor-bound protein 2 (Grb2):Son of Sevenless (SOS) networks, derived from the T-cell receptor signaling system, on supported membranes...
July 19, 2016: Proceedings of the National Academy of Sciences of the United States of America
Hyo Jung Kim, Jiyoung Y Cha, Jo Woon Seok, Yoonjeong Choi, Bo Kyung Yoon, Hyeonjin Choi, Jung Hwan Yu, Su Jin Song, Ara Kim, Hyemin Lee, Daeun Kim, Ji Yoon Han, Jae-Woo Kim
Glucocorticoids are associated with obesity, but the underlying mechanism by which they function remains poorly understood. Previously, we showed that small G protein Dexras1 is expressed by glucocorticoids and leads to adipocyte differentiation. In this study, we explored the mechanism by which Dexras1 mediates adipogenesis and show a link to the insulin-like growth factor-1 (IGF-1) signaling pathway. Without Dexras1, the activation of MAPK and subsequent phosphorylation of CCAAT/enhancer binding protein β (C/EBPβ) is abolished, thereby inhibiting mitotic clonal expansion and further adipocyte differentiation...
2016: Scientific Reports
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