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https://www.readbyqxmd.com/read/28110316/insensitivity-of-pi3k-akt-gsk3-signaling-in-peripheral-blood-mononuclear-cells-of-age-related-macular-degeneration-patients
#1
Liu Xunxian, Yao Zemin
Our recent studies with cultured retinal pigment epithelium cells suggested that overexpression of interleukin 17 receptor C (IL-17RC), a phenomenon observed in peripheral blood and chorioretinal tissues with age-related macular degeneration (AMD), was associated with altered activation of phosphatidylinositide 3-kinase (PI3K), Akt, and glycogen synthase kinase 3 (GSK3). We wondered whether or not altered PI3K, Akt, and GSK3 activities could be detected in peripheral blood mononuclear cells (PBMC) obtained from AMD patients...
January 19, 2017: Journal of Biomedical Research
https://www.readbyqxmd.com/read/28109086/grade-dependent-expression-of-nima-related-kinase-2-in-glioma-and-its-cellular-upregulatory-activity-on-proliferation-and-invasion
#2
Li Tian, Peng Cheng, Huaiyu Sun, Yulin Wang, Lei Zhang, Zongze Guo
Glioma is one of the most common tumors in central nervous system. The median life expectancy for glioma patients is only 13-15 months. NIMA-related expressed kinase 2 (NEK2) is a kind of serine-threonine kinases and involves in carcinogenesis and progression of cancer, however, the specific roles in the glioma remains unknown. We found the high expression of NEK2 was positively correlated with deteriorated severity of glioma. Therefore, we sought to investigate the effects of NEK2 on U87 and U251 cells. To explore the expression of NEK2 and alteration of signaling pathway factors, qRT-PCR and Western blot analysis were performed...
January 20, 2017: Oncology Research
https://www.readbyqxmd.com/read/28109038/lectin-complement-pathway-molecules-are-decreased-in-patients-with-cirrhosis-and-constitute-the-risk-of-bacterial-infections
#3
Ildiko Foldi, Tamas Tornai, David Tornai, Nora Sipeki, Zsuzsanna Vitalis, Istvan Tornai, Tamas Dinya, Peter Antal-Szalmas, Maria Papp
BACKGROUND&AIMS: Lectin pathway molecules of the complement system are synthesized by hepatocytes and have pivotal role in innate host defense against infectious organisms. Ficolins(FCNs) act as soluble pattern recognition molecules, while mannan-binding lectin serine proteases(MASPs) do as effector molecules in elimination of pathogens. We aimed to study the significance of low level of these molecules in the development of cirrhosis-associated bacterial infections, which has not been elucidated so far...
January 20, 2017: Liver International: Official Journal of the International Association for the Study of the Liver
https://www.readbyqxmd.com/read/28108628/metabolic-reprogramming-by-folate-restriction-leads-to-a-less-aggressive-cancer-phenotype
#4
Zahra Ashkavand, Ciara O'Flanagan, Mirko Hennig, Xiuxia Du, Stephen D Hursting, Sergey A Krupenko
: Folate coenzymes are involved in biochemical reactions of one-carbon transfer, and deficiency of this vitamin impairs cellular proliferation, migration, and survival in many cell types. Here, the effect of folate restriction on mammary cancer was evaluated using three distinct breast cancer subtypes differing in their aggressiveness and metastatic potential: noninvasive basal-like (E-Wnt), invasive but minimally metastatic claudin-low (M-Wnt), and highly metastatic claudin-low (metM-Wnt(liver)) cell lines, each derived from the same pool of MMTV-Wnt-1 transgenic mouse mammary tumors...
January 20, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28108287/antitumor-activity-of-a-novel-and-orally-available-inhibitor-of-serine-palmitoyltransferase
#5
Masahiro Yaguchi, Sachio Shibata, Yoshinori Satomi, Megumi Hirayama, Ryutaro Adachi, Yasutomi Asano, Takuto Kojima, Yasuhiro Hirata, Akio Mizutani, Atsushi Kiba, Yoji Sagiya
Metabolic reprogramming is an essential hallmark of neoplasia. Therefore, targeting cancer metabolism, including lipid synthesis, has attracted much interest in recent years. Serine palmitoyltransferase (SPT) plays a key role in the initial and rate-limiting step of de novo sphingolipid biosynthesis, and inhibiting SPT activity prevents the proliferation of certain cancer cells. Here, we identified a novel and orally available SPT inhibitor, compound-2. Compound-2 showed an anti-proliferative effect in several cancer cell models, reducing the levels of the sphingolipids ceramide and sphingomyelin...
January 17, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28107674/mitochondrial-serine-hydroxymethyltransferase-2-is-a-potential-diagnostic-and-prognostic-biomarker-for-human-glioma
#6
Bo Wang, Wei Wang, ZhiZhong Zhu, XueBin Zhang, Fan Tang, Dong Wang, Xi Liu, XiaoLing Yan, Hao Zhuang
OBJECTIVE: Scholars have gradually come to appreciate the relevance of serine and glycine metabolism. Recently, researchers have discovered that mitochondrial serine hydroxymethyltransferase 2 (SHMT2) is overexpressed in various types of cancer. However, the function of SHMT2 in glioma is not clear. In this study, we sought to examine the expression of SHMT2 in glioma, the association between SHMT2 expression and clinicopathological characteristics, and the association of SHMT2 expression with prognosis in glioma patients...
January 16, 2017: Clinical Neurology and Neurosurgery
https://www.readbyqxmd.com/read/28107427/serine-phosphorylation-of-slp76-is-dispensable-for-t-cell-development-but-modulates-helper-t-cell-function
#7
Victor H Navas, Céline Cuche, Andres Alcover, Vincenzo Di Bartolo
The adapter protein SLP76 is a key orchestrator of T cell receptor (TCR) signal transduction. We previously identified a negative feedback loop that modulates T cell activation, involving phosphorylation of Ser376 of SLP76 by the hematopoietic progenitor kinase 1 (HPK1). However, the physiological relevance of this regulatory mechanism was still unknown. To address this question, we generated a SLP76-S376A-expressing knock-in mouse strain and investigated the effects of Ser376 mutation on T cell development and function...
2017: PloS One
https://www.readbyqxmd.com/read/28107201/homeodomain-interacting-protein-kinase-2-hipk2-a-promising-target-for-anti-cancer-therapies
#8
Yuanyuan Feng, Lihong Zhou, Xiaoting Sun, Qi Li
The HIPK2 (serine/threonine homeodomain-interacting protein kinase 2) is a "caretaker" gene, its inactivation increases tumorigenicity while its activation inhibits tumor growth. This report reviews the anti-tumorigenic mechanisms of HIPK2, which include promotion of apoptosis, inhibition of angiogenesis in hypoxia, prevention of tumor invasion/metastasis and attenuation of multidrug resistance in cancer. Additionally, we summarize conditions or factors that may increase HIPK2 activity.
January 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28106735/mass-spectrometry-based-metabolomic-and-lipidomic-analyses-of-the-effects-of-dietary-platycodon-grandiflorum-on-liver-and-serum-of-obese-mice-under-a-high-fat-diet
#9
Hye Min Park, Kab-Tae Park, Edmond Changkyun Park, Seung Ii Kim, Myung Sook Choi, Kwang-Hyeon Liu, Choong Hwan Lee
We aimed to identify metabolites involved in the anti-obesity effects of Platycodon grandiflorum (PG) in high-fat diet (HFD)-fed mice using mass spectrometry (MS)-based metabolomic techniques. C57BL/6J mice were divided into four groups: normal diet (ND)-fed mice, HFD-fed mice, HFD with 1% PG extract-fed mice (HPGL), and HFD with 5% PG extract-fed mice (HPGH). After 8 weeks, the HFD group gained more weight than the ND group, while dietary 5% PG extract attenuated this change. The partial least squares discriminant analysis (PLS-DA) score plots showed a clear distinction between experimental groups in serum and liver markers...
January 17, 2017: Nutrients
https://www.readbyqxmd.com/read/28106377/chemical-proteomics-maps-brain-region-specific-activity-of-endocannabinoid-hydrolases
#10
Marc P Baggelaar, Annelot van Esbroeck, Eva van Rooden, Bogdan I Florea, Herman S Overkleeft, Giovanni Marsicano, Francis Chaouloff, Mario van der Stelt
The biosynthetic and catabolic enzymes of the endocannabinoids tightly regulate endocannabinoid-mediated activation of the cannabinoid CB1 receptor. Monitoring the activities of these endocannabinoid hydrolases in different brain regions is, therefore, key to gain insight in spatiotemporal control of CB1 receptor-mediated physiology. We have employed a comparative chemical proteomics approach to quantitatively map the activity profile of endocannabinoid hydrolases in various mouse brain regions at the same time...
January 20, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28106328/on-the-influence-of-the-protonation-states-of-active-site-residues-on-ache-reactivation-a-qm-mm-approach
#11
Thomas Driant, Florian Nachon, Cyril Ollivier, Pierre-Yves Renard, Etienne Derat
Acetylcholinesterase (AChE) is an enzyme of the serine hydrolase superfamily and a mediator of the signal transmission at cholinergic synapses catalysing acetylcholine cleavage into an acetate and a choline. This enzyme is vulnerable to covalent inhibition by organophosphate compounds (like VX). The covalent inhibition of AChE does not revert spontaneously and in order to restore catalytic activity known reactivator compounds have limited action. Simulations of VX-inhibited AChE reactivation by pralidoxime, a classical reactivator, were performed by QM/MM...
January 19, 2017: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/28105936/pathways-of-aging-comparative-analysis-of-gene-signatures-in-replicative-senescence-and-stress-induced-premature-senescence
#12
Kamil C Kural, Neetu Tandon, Mikhail Skoblov, Olga V Kel-Margoulis, Ancha V Baranova
BACKGROUND: In culturing normal diploid cells, senescence may either happen naturally, in the form of replicative senescence, or it may be a consequence of external challenges such as oxidative stress. Here we present a comparative analysis aimed at reconstruction of molecular cascades specific for replicative (RS) and stressinduced senescence (SIPS) in human fibroblasts. RESULTS: An involvement of caspase-3/keratin-18 pathway and serine/threonine kinase Aurora A/ MDM2 pathway was shared between RS and SIPS...
December 28, 2016: BMC Genomics
https://www.readbyqxmd.com/read/28105535/the-neuropeptide-orexin-a-inhibits-the-gabaa-receptor-by-pkc-and-ca-2-camkii-dependent-phosphorylation-of-its-%C3%AE-1-subunit
#13
Divya Sachidanandan, Haritha P Reddy, Anitha Mani, Geoffrey J Hyde, Amal Kanti Bera
Orexin-A and orexin-B (Ox-A, Ox-B) are neuropeptides produced by a small number of neurons that originate in the hypothalamus and project widely in the brain. Only discovered in 1998, the orexins are already known to regulate several behaviours. Most prominently, they help to stabilise the waking state, a role with demonstrated significance in the clinical management of narcolepsy and insomnia. Orexins bind to G-protein-coupled receptors (predominantly postsynaptic) of two subtypes, OX1R and OX2R. The primary effect of Ox-OXR binding is a direct depolarising influence mediated by cell membrane cation channels, but a wide variety of secondary effects, both pre- and postsynaptic, are also emerging...
January 19, 2017: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/28105234/interaction-of-cyclophilin-a-with-a-novel-binding-protein-sr-25-and-characterization-of-their-expression-pattern-in-chinese-hepatocellular-carcinoma-patients
#14
Jian Chen, Ning Li, Peiwen Lian, Jiahui Wang, Peng Li, Zhaohua Gong, Lixin Jiang
Cyclophilin (Cyp) A has been reported to be overexpressed in the majority of cancer cells, including hepatocellular carcinoma (HCC). However, the biological functions of CypA in HCC are far from being understood. To determine the biological functions of CypA in HCC, the present study screened human fetal liver complementary DNA for proteins interacting with CypA using the yeast two-hybrid system. A nuclear protein, serine/arginine-rich (SR)-25, was isolated as a novel CypA-binding protein that is distinct from those previously described in the literature...
December 2016: Oncology Letters
https://www.readbyqxmd.com/read/28105216/identification-of-potential-therapeutic-targets-for-colorectal-cancer-by-bioinformatics-analysis
#15
Ming Yan, Maomin Song, Rixing Bai, Shi Cheng, Wenmao Yan
The aim of the present study was to identify potential therapeutic targets for colorectal cancer (CRC). The gene expression profile GSE32323, containing 34 samples, including 17 specimens of CRC tissues and 17 of paired normal tissues from CRC patients, was downloaded from the Gene Expression Omnibus database. Following data preprocessing using the Affy and preprocessCore packages, the differentially-expressed genes (DEGs) between the two types of samples were identified with the Linear Models for Microarray Analysis package...
December 2016: Oncology Letters
https://www.readbyqxmd.com/read/28104818/structure-and-activation-of-c1-the-complex-initiating-the-classical-pathway-of-the-complement-cascade
#16
Simon A Mortensen, Bjoern Sander, Rasmus K Jensen, Jan Skov Pedersen, Monika M Golas, Jens C Jensenius, Annette G Hansen, Steffen Thiel, Gregers R Andersen
The complement system is an important antimicrobial and inflammation-generating component of the innate immune system. The classical pathway of complement is activated upon binding of the 774-kDa C1 complex, consisting of the recognition molecule C1q and the tetrameric protease complex C1r2s2, to a variety of activators presenting specific molecular patterns such as IgG- and IgM-containing immune complexes. A canonical model entails a C1r2s2 with its serine protease domains tightly packed together in the center of C1 and an intricate intramolecular reaction mechanism for activation of C1r and C1s, induced upon C1 binding to the activator...
January 19, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28104399/structural-basis-for-the-regulation-of-nuclear-import-of-epstein-barr-virus-nuclear-antigen-1-ebna1-by-phosphorylation-of-the-nuclear-localization-signal
#17
Ryohei Nakada, Hidemi Hirano, Yoshiyuki Matsuura
Epstein-Barr virus (EBV) nuclear antigen 1 (EBNA1) is expressed in every EBV-positive tumor and is essential for the maintenance, replication, and transcription of the EBV genome in the nucleus of host cells. EBNA1 is a serine phosphoprotein, and it has been shown that phosphorylation of S385 in the nuclear localization signal (NLS) of EBNA1 increases the binding affinity to the nuclear import adaptor importin-α1 as well as importin-α5, and stimulates nuclear import of EBNA1. To gain insights into how phosphorylation of the EBNA1 NLS regulates nuclear import, we have determined the crystal structures of two peptide complexes of importin-α1: one with S385-phosphorylated EBNA1 NLS peptide, determined at 2...
January 16, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28104354/profound-loss-of-esophageal-tissue-differentiation-in-eosinophilic-esophagitis
#18
M Rochman, J Travers, C E Miracle, M C Bedard, T Wen, N P Azouz, J M Caldwell, K Kc, J D Sherrill, B P Davis, J K Rymer, K M Kaufman, M E Rothenberg
BACKGROUND: A key question in the allergy field is to understand how tissue specific disease is manifested. Eosinophilic esophagitis (EoE) is an emerging tissue specific allergic disease whose pathogenesis remains unclear. OBJECTIVE: Herein, we tested the hypothesis that a defect in tissue specific esophageal genes is an integral part of EoE pathogenesis. METHODS: We interrogated the pattern of expression of esophagus-specific signature genes derived from the Human Protein Atlas in the EoE transcriptome and in EPC2 esophageal epithelial cells...
January 16, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28103160/yersinia-pestis-acetyltransferase-mediated-dual-acetylation-at-the-serine-and-lysine-residues-enhances-the-auto-ubiquitination-of-ubiquitin-ligase-march8-in-human-cells
#19
Cuiling Li, Daoguang Wang, Xin Lv, Ruirui Jing, Baibin Bi, Xinjun Chen, Jisheng Guo, Fengqin Wang, Shengnan Sun, Kazem M Azadzoi, Jing-Hua Yang
Lysine acetylation is known as a post translational modification (PTM) by histone acetyltransferases (HAT) that modifies histones and non-histone proteins to regulate gene expression. Serine acetylation, however, is reported in mammalian hosts by serine acetyltransferase of Yersinia pestis (YopJ) during infection. The protein target and cellular function of bacterial YopJ in mammalian systems are not fully addressed. Here we report dual acetylation at the serine and lysine residues by transiently expressed serine acetyltransferase YopJ mimicking Y...
January 19, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28103011/discovery-of-a-phosphonoacetic-acid-derived-natural-product-by-pathway-refactoring
#20
Todd S Freestone, Kou-San Ju, Bin Wang, Huimin Zhao
The activation of silent natural product gene clusters is a synthetic biology problem of great interest. As the rate at which gene clusters are identified outpaces the discovery rate of new molecules, this unknown chemical space is rapidly growing, as too are the rewards for developing technologies to exploit it. One class of natural products that has been underrepresented is phosphonic acids, which have important medical and agricultural uses. Hundreds of phosphonic acid biosynthetic gene clusters have been identified encoding for unknown molecules...
January 19, 2017: ACS Synthetic Biology
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