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https://www.readbyqxmd.com/read/28333195/genome-wide-genetic-analyses-highlight-mitogen-activated-protein-kinase-mapk-signaling-in-the-pathogenesis-of-endometriosis
#1
Outi Uimari, Nilufer Rahmioglu, Dale R Nyholt, Katy Vincent, Stacey A Missmer, Christian Becker, Andrew P Morris, Grant W Montgomery, Krina T Zondervan
STUDY QUESTION: Do genome-wide association study (GWAS) data for endometriosis provide insight into novel biological pathways associated with its pathogenesis? SUMMARY ANSWER: GWAS analysis uncovered multiple pathways that are statistically enriched for genetic association signals, analysis of Stage A disease highlighted a novel variant in MAP3K4, while top pathways significantly associated with all endometriosis and Stage A disease included several mitogen-activated protein kinase (MAPK)-related pathways...
February 9, 2017: Human Reproduction
https://www.readbyqxmd.com/read/28331335/microrna-543-suppresses-breast-cancer-cell-proliferation-blocks-cell-cycle-and-induces-cell-apoptosis-via-direct-targeting-of-erk-mapk
#2
Po Chen, Wentao Xu, Yi Luo, Yi Zhang, Yi He, Shuo Yang, Zhijun Yuan
BACKGROUND: Breast cancer affects millions of people with a high mortality rate throughout the world; microRNA 543 (miR-543) has been reported to suppress progression in some kinds of cancers, but has not been reported in breast cancer. Thus, the purpose of this study is to investigate the function of miR-543 in breast cancer cells. METHODS: Two cell lines, MCF-7 and MDA-MB-231, were selected to be the research objects; the miR-543 overexpression and knockdown models were established in the study by transforming miR-543 mimics and miR-543 inhibitor...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28322346/resveratrol-mitigates-lipopolysaccharide-mediated-acute-inflammation-in-rats-by-inhibiting-the-tlr4-nf-%C3%AE%C2%BAbp65-mapks-signaling-cascade
#3
Guangxi Wang, Zhiqiang Hu, Qiuting Fu, Xu Song, Qiankun Cui, Renyong Jia, Yuanfeng Zou, Changliang He, Lixia Li, Zhongqiong Yin
Resveratrol (RSV) is a natural compound exhibiting anti-inflammatory effect, but the anti-inflammatory mechanism has not been fully understood. This study is aimed to evaluate the anti-inflammatory activity and mechanism of RSV in lipopolysaccharides-induced rats' model. The visceral wet/dry weight ratios and the changes of hematologic and biochemical indices indicated that LPS- stimulation mainly caused damages to liver and lung, while pretreatment with RSV could alleviate the lesions. The cytokine assays showed that RSV could markedly decrease the production of proinflammatory mediators and cytokines (IL-1, IL-1β, IL-6, NO, iNOS and COX-2), and increase the expression of anti-inflammatory mediator (IL-10)...
March 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28302472/erk1-and-erk2-activation-modulates-diet-induced-obesity-in-mice
#4
Amira Sayed Khan, Selvakumar Subramaniam, Gado Dramane, Douadi Khelifi, Naim Akhtar Khan
Obesity is a worldwide problem, and dietary lipids play an important role in its pathogenesis. Recently, Erk1 knock-out (ERK1(-/-)) mice have been shown to exhibit low preference for dietary fatty acids. Hence, we maintained Erk1(-/-) mice on a high-fat diet (HFD) to assess the implication of this mitogen-activated protein (MAP) kinase in obesity. The Erk1(-/-) mice, fed the HFD, were more obese than wild-type (WT) animals, fed the same diet. Erk1(-/-) obese mice gained more fat and liver mass than WT obese animals...
March 13, 2017: Biochimie
https://www.readbyqxmd.com/read/28274314/-inhibitory-effect-of-magnesium-cantharidate-on-human-hepatoma-smmc-7721-cell-proliferation-by-blocking-mapk-signaling-pathway
#5
Yun Liu, Xiaofei Li, Qianqian Zou, Liu Liu, Xinting Zhu, Qi Jia, Lingjun Wang, Rong Yan
Objective To investigate the anticancer mechanism of magnesium cantharidate by observing its effect on the mitogen-activated protein kinase (MAPK) signaling pathway in human hepatoma SMMC-7721 cells. Methods The protein phosphatase 2A (PP2A) activity detection kit was used to detect the effects of magnesium cantharidate and okadaic acid (OA) on PP2A activity. After the treatment of SMMC-7721 cells with magnesium cantharidate and/or OA, mRNA levels of extracellular signal-regulated kinase 1 (ERK1), ERK2, p38MAPK, c-Jun N-terminal kinase 1 (JNK1) and JNK2 were detected by real-time quantitative PCR, and the protein expression levels and protein phosphorylation of ERK1, ERK2, p38 MAPK and JNK were determined by Western blotting...
March 2017: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
https://www.readbyqxmd.com/read/28274095/sphingosylphosphorylcholine-induces-thrombospondin-1-secretion-in-mcf10a-cells-via-erk2
#6
June Hee Kang, Hyun Ji Kim, Mi Kyung Park, Chang Hoon Lee
Sphingosylphosphorylcholine (SPC) is one of the bioactive phospholipids that has many cellular functions such as cell migration, adhesion, proliferation, angiogenesis, and Ca²⁺ signaling. Recent studies have reported that SPC induces invasion of breast cancer cells via matrix metalloproteinase-3 (MMP-3) secretion leading to WNT activation. Thrombospondin-1 (TSP-1) is a matricellular and calcium-binding protein that binds to a wide variety of integrin and non-integrin cell surface receptors. It regulates cell proliferation, migration, and apoptosis in inflammation, angiogenesis and neoplasia...
March 10, 2017: Biomolecules & Therapeutics
https://www.readbyqxmd.com/read/28262736/knockdown-of-the-mapk-p38-pathway-increases-the-susceptibility-of-chilo-suppressalis-larvae-to-bacillus-thuringiensis-cry1ca-toxin
#7
Lin Qiu, Jinxing Fan, Lang Liu, Boyao Zhang, Xiaoping Wang, Chaoliang Lei, Yongjun Lin, Weihua Ma
The bacterium Bacillus thuringiensis (Bt) produces a wide range of toxins that are effective against a number of insect pests. Identifying the mechanisms responsible for resistance to Bt toxin will improve both our ability to control important insect pests and our understanding of bacterial toxicology. In this study, we investigated the role of MAPK pathways in resistance against Cry1Ca toxin in Chilo suppressalis, an important lepidopteran pest of rice crops. We first cloned the full-length of C. suppressalis mitogen-activated protein kinase (MAPK) p38, ERK1, and ERK2, and a partial sequence of JNK (hereafter Csp38, CsERK1, CsERK2 and CsJNK)...
March 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28260027/pstat5-and-erk-exhibit-different-expression-in-myeloproliferative-neoplasms
#8
Ewa Wiśniewska-Chudy, Łukasz Szylberg, Grzegorz Dworacki, Ewa Mizera-Nyczak, Andrzej Marszałek
Myeloproliferative neoplasms (MPNs) are clonal hematopoietic progenitor cell disorders characterized by the proliferation of one or more hematopoietic lineages. The classical MPNs include polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF) entities. These disorders are characterized by bone marrow morphology typical for each disease, and by the presence of JAK2V617F mutation in the marrow and blood. However, JAK2V617F cannot account for the phenotypic heterogeneity of MPNs because approximately half of all cases of ET and PMF show no evidence of this molecular marker...
February 24, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28230313/crosstalk-between-smad2-3-and-specific-isoforms-of-erk-in-tgf-%C3%AE-1-induced-timp-3-expression-in-rat-chondrocytes
#9
Yanhui Zhu, Jianhua Gu, Tong Zhu, Chen Jin, Xiaopeng Hu, Xiang Wang
This study investigated the roles of ERK1 and ERK2 in transforming growth factor-β1 (TGF-β1)-induced tissue inhibitor of metalloproteinases-3 (TIMP-3) expression in rat chondrocytes, and the specific roles of ERK1 and ERK2 in crosstalk with Smad2/3 were investigated to demonstrate the molecular mechanism of ERK1/2 regulation of TGF-β1 signalling. To examine the interaction of specific isoforms of ERK and the Smad2/3 signalling pathway, chondrocytes were infected with LV expressing either ERK1 or ERK2 siRNA and stimulated with or without TGF-β1...
February 23, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28228552/core-engagement-with-%C3%AE-arrestin-is-dispensable-for-agonist-induced-vasopressin-receptor-endocytosis-and-erk-activation
#10
Punita Kumari, Ashish Srivastava, Eshan Ghosh, Ravi Ranjan, Shalini Dogra, Prem N Yadav, Arun K Shukla
G Protein-Coupled Receptors (GPCRs) exhibit highly conserved activation and signaling mechanisms where agonist stimulation leads to coupling of heterotrimeric G proteins and generation of second messenger response. This is followed by receptor phosphorylation, primarily in the carboxyl-terminus but also in the cytoplasmic loops, and subsequent binding of arrestins. GPCRs typically recruit arrestins through two different set of interactions, one involving phosphorylated receptor tail and the other mediated by the receptor core...
February 22, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28218497/chemotherapy-induces-tumor-immune-evasion-by-upregulation-of-programmed-cell-death-ligand%C3%A2-1-expression-in-bone-marrow-stromal-cells
#11
Mengqi Yang, Panpan Liu, Kefeng Wang, Christophe Glorieux, Yumin Hu, Shijun Wen, Wenqi Jiang, Peng Huang
Programmed cell death ligand 1 (PD-L1) is a negative regulator of the immune response that enables tumor cells to escape T-cell immunity. Although PD-L1 expression in cancer cells has been extensively studied, the expression of PD-L1 in stromal cells and its clinical significance remain largely unknown. Here, we show that bone marrow stromal cells express a low level of PD-L1 and that this molecule is significantly upregulated by key drugs used in the treatment of lymphoma at clinically relevant concentrations...
December 28, 2016: Molecular Oncology
https://www.readbyqxmd.com/read/28197631/repositioning-of-amprenavir-as-a-novel-extracellular-signal-regulated-kinase-2-inhibitor-and-apoptosis-inducer-in-mcf-7-human-breast-cancer
#12
Wenchun Jiang, Xin Li, Tongyu Li, Hailian Wang, Wei Shi, Ping Qi, Chunyang Li, Jie Chen, Jinku Bao, Guodong Huang, Yi Wang
Computational drug repositioning by virtually screening existing drugs for additional therapeutic usage could efficiently accelerate anticancer drug discovery. Herein, a library of 1447 Food and Drug Administration (FDA)-approved small molecule drugs was screened in silico for inhibitors of extracellular signal-regulated kinase 2 (ERK2). Then, in vitro kinase assay demonstrated amprenavir, a HIV-1 protease inhibitor, as a potential kinase inhibitor of ERK2. The in vivo kinase assay indicated that amprenavir could inhibit ERK2-mediated phosphorylation of BimEL at Ser69...
March 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28193531/mutation-of-a-putative-map-kinase-consensus-site-regulates-ncam-endocytosis-and-ncam-dependent-neurite-outgrowth
#13
Tobias Goschzik, Harold Cremer, Vinayaga S Gnanapragassam, Rüdiger Horstkorte, Kaya Bork, Simone Diestel
The cytoplasmic domain of the neural cell adhesion molecule NCAM contains several putative serine/threonine phosphorylation sites whose functions are largely unknown. Human NCAM140 (NCAM140) possesses a potential MAP kinase phosphorylation site at threonine (T) 803. The aim of this study was to analyze a possible phosphorylation of NCAM140 by MAP kinases and to identify the functional role of T803. We found that NCAM140 is phosphorylated by the MAP kinase ERK2 in vitro. Exchange of T803 to aspartic acid (D) which mimics constitutive phosphorylation at the respective position resulted in increased endocytosis compared to NCAM140 in neuroblastoma cells and primary neurons...
February 10, 2017: Neuroscience Research
https://www.readbyqxmd.com/read/28192403/a-double-negative-feedback-loop-between-epcam-and-erk-contributes-to-the-regulation-of-epithelial-mesenchymal-transition-in-cancer
#14
N V Sankpal, T P Fleming, P K Sharma, H J Wiedner, W E Gillanders
Epithelial-mesenchymal transition (EMT) is an important biological process that has been implicated in cancer metastasis. Epithelial cell adhesion molecule (EpCAM) is expressed at the basolateral membrane of most normal epithelial cells but is overexpressed in many epithelial cancers. In our studies on the role of EpCAM in cancer biology, we observed that EpCAM expression is decreased in mesenchymal-like primary cancer specimens in vivo and following induction of EMT in cancer cell lines in vitro. Extracellular signal-related kinase (ERK) is a key regulator of EMT...
February 13, 2017: Oncogene
https://www.readbyqxmd.com/read/28183201/effect-of-titanium-dioxide-nanoparticles-tio2-nps-on-the-expression-of-mucin-genes-in-human-airway-epithelial-cells
#15
Gui Ok Kim, Yoon Seok Choi, Chang Hoon Bae, Si-Youn Song, Yong-Dae Kim
OBJECTIVE: Titanium dioxide nanoparticles (TiO2 NPs) are utilized with growing frequency for a wide variety of industrial applications. Recently, acute and chronic exposures to TiO2 NPs have been found to induce inflammatory response in the human respiratory tract. However, the effect and mechanism underlying the induction of major airway mucins by TiO2 NPs have not been elucidated. This study was conducted to characterize the effect of TiO2 NPs, and the mechanism involved, on the expressions of airway mucins in human airway epithelial cells...
January 2017: Inhalation Toxicology
https://www.readbyqxmd.com/read/28174228/profiling-subcellular-protein-phosphatase-responses-to-coxsackievirus-b3-infection-of-cardiomyocytes
#16
Millie Shah, Christian M Smolko, Sarah Kinicki, Zachary D Chapman, David L Brautigan, Kevin A Janes
Cellular responses to stimuli involve dynamic and localized changes in protein kinases and phosphatases. Here, we report a generalized functional assay for high-throughput profiling of multiple protein phosphatases with subcellular resolution and apply it to analyze coxsackievirus B3 (CVB3) infection counteracted by interferon signaling. Using on-plate cell fractionation optimized for adherent cells, we isolate protein extracts containing active endogenous phosphatases from cell membranes, the cytoplasm, and the nucleus...
February 7, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28168209/familial-amyloid-polyneuropathy-in-portugal-new-genes-modulating-age-at-onset
#17
Diana Santos, Teresa Coelho, Miguel Alves-Ferreira, Jorge Sequeiros, Denisa Mendonça, Isabel Alonso, Carolina Lemos, Alda Sousa
OBJECTIVES: Familial amyloid polyneuropathy (FAP ATTRV30M) shows a wide variation in age-at-onset (AO) between clusters, families, and among generations. We will now explore some candidate genes involved in altered disease pathways in order to assess their role as genetic modifiers of AO, using a family-centered approach. METHODS: We analyzed 62 tagging SNPs from nine genes-NGAL,MMP-9,BGN,MEK1,MEK2,ERK1,ERK2,HSP27, and YWHAZ - in a sample of 318 V30M Portuguese patients (106 families), currently under follow-up...
February 2017: Annals of Clinical and Translational Neurology
https://www.readbyqxmd.com/read/28160492/a-prognostic-4-gene-expression-signature-for-squamous-cell-lung-carcinoma
#18
Jun Li, Jing Wang, Yanbin Chen, Lijie Yang, Sheng Chen
Squamous cell lung carcinoma (SQCLC), a common and fatal subtype of lung cancer, caused lots of mortalities and showed different outcomes in prognosis. This study was to screen key genes and to figure a prognostic signature to cluster the patients with SQCLC. RNA-Seq data from 550 patients with SQCLC were downloaded from The Cancer Genome Atlas (TCGA). Genetically changed genes were identified and analyzed in univariate survival analysis. Genes significantly influencing prognosis were selected with frequency higher than 100 in lasso regression...
February 4, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28145992/different-effects-of-prenatal-stress-on-erk2-creb-bcl-2-expression-in-the-hippocampus-and-the-prefrontal-cortex-of-adult-offspring-rats
#19
Zeen Zhu, Hongli Sun, Xiaojie Gong, Hui Li
It has become increasingly evident that prenatal stress and its psychological and physiological concomitants are associated with the pathophysiology of mood disorders. However, the mechanisms underlying the prenatal stress-induced offspring's anxiety disorders remain unknown. We recently reported that prenatal stress enhanced anxiety-like behavior in adult offspring rat, and involved N-methyl-D-aspartate receptor subunits, including NR1 and NR2A. In the present research, using the same prenatal stress model, we measured the ERK2/CREB/Bcl-2 mRNA levels by real-time PCR...
January 31, 2017: Neuroreport
https://www.readbyqxmd.com/read/28119463/erk-signaling-pathway-regulates-sleep-duration-through-activity-induced-gene-expression-during-wakefulness
#20
Cyril Mikhail, Angélique Vaucher, Sonia Jimenez, Mehdi Tafti
Wakefulness is accompanied by experience-dependent synaptic plasticity and an increase in activity-regulated gene transcription. Wake-induced genes are certainly markers of neuronal activity and may also directly regulate the duration of and need for sleep. We stimulated murine cortical cultures with the neuromodulatory signals that are known to control wakefulness in the brain and found that norepinephrine alone or a mixture of these neuromodulators induced activity-regulated gene transcription. Pharmacological inhibition of the various signaling pathways involved in the regulation of gene expression indicated that the extracellular signal-regulated kinase (ERK) pathway is the principal one mediating the effects of waking neuromodulators on gene expression...
January 24, 2017: Science Signaling
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