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https://www.readbyqxmd.com/read/29322785/triptolide-induces-mitochondrial-apoptosis-through-modulating-dual-specificity-phosphatase-1-mitogen-activated-protein-kinases-cascade-in-osteosarcoma-cells
#1
W Qin, S Li, Y Miao, Q Shi, Y Wang, J Li, Z Chen, J Wang, C Ling
Due to chemoresistance and metastasis, the overall prognosis of osteosarcoma (OS) has not improved over the last two decades. Exploring novel therapeutic agents that can circumvent theses malignant phenotypes of OS would be essential to improve the survival of OS patients. Triptolide is a unique diterpene triepoxide that possesses potent antitumor activities.However, the effects and mechanism of triptolide on OS cells remain unknown. The effects of triptolide on viability, apoptosis, cell cycle distribution and migratory ability of OS cells were measured using MTT, flow cytometry and wound healing and transwell invasion assays...
2018: Neoplasma
https://www.readbyqxmd.com/read/29284798/high-expression-of-mkp1-dusp1-counteracts-glioma-stem-cell-activity-and-mediates-hdac-inhibitor-response
#2
Olatz Arrizabalaga, Leire Moreno-Cugnon, Jaione Auzmendi-Iriarte, Paula Aldaz, Inmaculada Ibañez de Cáceres, Laura Garros-Regulez, Veronica Moncho-Amor, Sergio Torres-Bayona, Olga Pernía, Laura Pintado-Berninches, Patricia Carrasco-Ramirez, María Cortes-Sempere, Rocío Rosas, Pilar Sanchez-Gomez, Irune Ruiz, Helena Caren, Steven Pollard, Idoia Garcia, Angel-Ayuso Sacido, Robin Lovell-Badge, Cristobal Belda-Iniesta, Nicolas Sampron, Rosario Perona, Ander Matheu
The elucidation of mechanisms involved in resistance to therapies is essential to improve the survival of patients with malignant gliomas. A major feature possessed by glioma cells that may aid their ability to survive therapy and reconstitute tumors is the capacity for self-renewal. We show here that glioma stem cells (GSCs) express low levels of MKP1, a dual-specificity phosphatase, which acts as a negative inhibitor of JNK, ERK1/2, and p38 MAPK, while induction of high levels of MKP1 expression are associated with differentiation of GSC...
December 14, 2017: Oncogenesis
https://www.readbyqxmd.com/read/29273751/excitotoxic-inactivation-of-constitutive-oxidative-stress-detoxification-pathway-in-neurons-can-be-rescued-by-pkd1
#3
Julia Pose-Utrilla, Lucía García-Guerra, Ana Del Puerto, Abraham Martín, Jerónimo Jurado-Arjona, Noelia S De León-Reyes, Andrea Gamir-Morralla, Álvaro Sebastián Serrano, Mónica García-Gallo, Leonor Kremer, Jens Fielitz, Christofer Ireson, Mª José Pérez-Álvarez, Isidro Ferrer, Félix Hernández, Jesús Ávila, Marina Lasa, Miguel R Campanero, Teresa Iglesias
Excitotoxicity, a critical process in neurodegeneration, induces oxidative stress and neuronal death through mechanisms largely unknown. Since oxidative stress activates protein kinase D1 (PKD1) in tumor cells, we investigated the effect of excitotoxicity on neuronal PKD1 activity. Unexpectedly, we find that excitotoxicity provokes an early inactivation of PKD1 through a dephosphorylation-dependent mechanism mediated by protein phosphatase-1 (PP1) and dual specificity phosphatase-1 (DUSP1). This step turns off the IKK/NF-κB/SOD2 antioxidant pathway...
December 22, 2017: Nature Communications
https://www.readbyqxmd.com/read/29251255/effects-of-genetic-factors-to-inhaled-corticosteroid-response-in-children-with-asthma-a-literature-review
#4
Huong Duong-Thi-Ly, Ha Nguyen-Thi-Thu, Long Nguyen-Hoang, Hanh Nguyen-Thi-Bich, Timothy J Craig, Sy Duong-Quy
Numerous studies have examined the association between pharmacogenetic effects and the response to inhaled corticosteroids (ICS) in patients with asthma. In fact, several single nucleotide polymorphisms of a number of candidate genes have been identified that might influence the clinical response to ICS in children with asthma. Their direct or indirect effects depend on their role in the inflammatory process in asthma or the anti-inflammatory action of corticosteroids, respectively. Among the genes identified, variants in T-box 21 ( TBX21) and Fc fragment of IgE receptor II ( FCER2) contribute indirectly to the variability in the response to ICS by altering the inflammatory mechanisms in asthma, while other genes such as corticotropin releasing hormone receptor 1 ( CRHR1), nuclear receptor subfamily 3 group C member 1 ( NR3C1), stress induced phosphoprotein 1 ( STIP1), dual specificity phosphatase 1 (DUSP1), glucocorticoid induced 1 (GLCCI1), histone deacetylase 1 (HDAC), ORMDL sphingolipid biosynthesis regulator 3 (ORMDL3), and vascular endothelial growth factors (VEGF) directly affect this variability through the anti-inflammatory mechanisms of ICS...
December 2017: Journal of International Medical Research
https://www.readbyqxmd.com/read/29234123/dusp1-regulates-apoptosis-and-cell-migration-but-not-the-jip1-protected-cytokine-response-during-respiratory-syncytial-virus-and-sendai-virus-infection
#5
Alexa C Robitaille, Elise Caron, Nicolas Zucchini, Espérance Mukawera, Damien Adam, Mélissa K Mariani, Anaïs Gélinas, Audray Fortin, Emmanuelle Brochiero, Nathalie Grandvaux
The host antiviral response involves the induction of interferons and proinflammatory cytokines, but also the activation of cell death pathways, including apoptosis, to limit viral replication and spreading. This host defense is strictly regulated to eliminate the infection while limiting tissue damage that is associated with virus pathogenesis. Post-translational modifications, most notably phosphorylation, are key regulators of the antiviral defense implying an important role of protein phosphatases. Here, we investigated the role of the dual-specificity phosphatase 1 (DUSP1) in the host defense against human respiratory syncytial virus (RSV), a pathogenic virus of the Pneumoviridae family, and Sendai virus (SeV), a model virus being developed as a vector for anti-RSV vaccine...
December 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29180230/glucocorticoids-genes-and-brain-function
#6
REVIEW
Grzegorz R Juszczak, Adrian M Stankiewicz
The identification of key genes in transcriptomic data constitutes a huge challenge. Our review of microarray reports revealed 88 genes whose transcription is consistently regulated by glucocorticoids (GCs), such as cortisol, corticosterone and dexamethasone, in the brain. Replicable transcriptomic data were combined with biochemical and physiological data to create an integrated view of the effects induced by GCs. The most frequently reported genes were Errfi1 and Ddit4. Their up-regulation was associated with the altered transcription of genes regulating growth factor and mTORC1 signaling (Gab1, Tsc22d3, Dusp1, Ndrg2, Ppp5c and Sesn1) and progression of the cell cycle (Ccnd1, Cdkn1a and Cables1)...
November 24, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/29149759/dusp1-alleviates-cardiac-ischemia-reperfusion-injury-by-suppressing-the-mff-required-mitochondrial-fission-and-bnip3-related-mitophagy-via-the-jnk-pathways
#7
Qinhua Jin, Ruibing Li, Nan Hu, Ting Xin, Pingjun Zhu, Shunying Hu, Sai Ma, Hong Zhu, Jun Ren, Hao Zhou
Mitochondrial fission and selective mitochondrial autophagy (mitophagy) form an essential axis of mitochondrial quality control that plays a critical role in the development of cardiac ischemia-reperfusion (IR) injury. However, the precise upstream molecular mechanism of fission/mitophagy remains unclear. Dual-specificity protein phosphatase1 (DUSP1) regulates cardiac metabolism, but its physiological contribution in the reperfused heart, particularly its influence on mitochondrial homeostasis, is unknown. Here, we demonstrated that cardiac DUSP1 was downregulated following acute cardiac IR injury...
November 6, 2017: Redox Biology
https://www.readbyqxmd.com/read/29133249/immunomodulation-of-dual-specificity-phosphatase-4-during-visceral-leishmaniasis
#8
Shabina Parveen, Atish Roy Chowdhury, Junaid Jibran Jawed, Suchandra Bhattacharyya Majumdar, Bhaskar Saha, Subrata Majumdar
DUSP4, an inducible protein has a substrate specificity toward ERK1/2, a component of MAP kinase which is enhanced during Leishmania infection. The DUSP4(-/-) mice show increased susceptibility towards the infection caused by Toxoplasma gondii and Leishmania mexicana. These observations emphatically established the fact that unlike DUSP1, DUSP4 has host protective role. In our study, it has been Leishmania donovani, the causative agent of visceral leishmaniasis (VL) significantly reduced the expression of DUSP4 during infection...
November 10, 2017: Microbes and Infection
https://www.readbyqxmd.com/read/29052270/crystal-structure-of-the-human-dual-specificity-phosphatase-1-catalytic-domain
#9
Rajesh Gumpena, George T Lountos, Sreejith Raran-Kurussi, Joseph E Tropea, Scott Cherry, David S Waugh
The dual specificity phosphatase DUSP1 was the first mitogen activated protein kinase phosphatase (MKP) to be identified. It dephosphorylates conserved tyrosine and threonine residues in the activation loops of mitogen activated protein kinases ERK2, JNK1 and p38-alpha. Here, we report the crystal structure of the human DUSP1 catalytic domain at 2.49 Å resolution. Uniquely, the protein was crystallized as an MBP fusion protein in complex with a monobody that binds to MBP. Sulfate ions occupy the phosphotyrosine and putative phosphothreonine binding sites in the DUSP1 catalytic domain...
October 20, 2017: Protein Science: a Publication of the Protein Society
https://www.readbyqxmd.com/read/29048612/regulation-of-erk-and-akt-pathways-by-hepatitis%C3%A2-b-virus%C3%A2-x-protein-via-the-notch1-pathway-in-hepatocellular-carcinoma
#10
Bo Liao, Honghao Zhou, Huifang Liang, Changhai Li
Hepatitis B virus (HBV) is the dominant risk factor for hepatocellular carcinoma (HCC). HBV X protein (HBx) plays crucial roles in HCC carcinogenesis. HBx interferes with several signaling pathways including the Notch1 pathway in HCC. In this study, we found that Notch1 was highly expressed in HCC, especially in large HCCs. Notch1 and HBx co-localized in HCC and their levels were positively correlated with each other. Notch1 expression was more elevated in HepG2.2.15 cells than that in HepG2 cells. HBx activated the Notch1 pathway in HepG2...
September 15, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28983624/dual-specificity-phosphatase-1-has-a-protective-role-in-osteoarthritis-fibroblast%C3%A2-like-synoviocytes-via-inhibition-of-the-mapk-signaling-pathway
#11
Hua-Zhi Peng, Zhe Yun, Wei Wang, Bao-An Ma
Increasing evidence indicates the important role of inflammation in the pathogenesis and progression of osteoarthritis (OA). Dual specificity phosphatase 1 (DUSP1), a negative regulator of the mitogen‑activated protein kinase (MAPK) signaling pathway, has anti‑inflammatory properties. In the present study, the expression of DUSP1 was investigated in human OA fibroblast‑like synoviocytes (FLSs), human normal FLSs and OA FLSs pretreated with dexamethasone at the mRNA and protein levels. Then, the activation of MAPK pathway proteins and the expression of matrix metalloproteinase‑13 (MMP‑13) and cyclooxygenase‑2 (COX‑2) were measured by western blot analysis in the three groups of cells...
December 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28861772/oral-health-may-affect-the-performance-of-mrna-based-saliva-biomarkers-for-oral-squamous-cell-cancer
#12
József Horváth, Adrien Szabó, Ildikó Tar, Balázs Dezső, Csongor Kiss, Ildikó Márton, Beáta Scholtz
Oral squamous cell carcinoma (OSCC) has a dismal 50% five-year survival rate, emphasizing the need to develop reliable and sensitive tools for early diagnosis. In this study we evaluated the performance of 7 previously identified, potential mRNA biomarkers of OSCC in saliva samples of Hungarian patients. Expression of the putative OSCC biomarkers (DUSP1, OAZ1, H3F3A, IL1B, IL8, SAT and S100P), 2 biomarkers of inflammation (IL6 and TNFα) and 8 putative normalizing genes was quantified from each sample using real-time quantitative PCR...
August 31, 2017: Pathology Oncology Research: POR
https://www.readbyqxmd.com/read/28822081/expression-profiling-of-the-map-kinase-phosphatase-family-reveals-a-role-for-dusp1-in-the-glioblastoma-stem-cell-niche
#13
Bradley N Mills, George P Albert, Marc W Halterman
The dual specificity phosphatases (DUSPs) constitute a family of stress-induced enzymes that provide feedback inhibition on mitogen-activated protein kinases (MAPKs) critical in key aspects of oncogenic signaling. While described in other tumor types, the landscape of DUSP mRNA expression in glioblastoma (GB) remains largely unexplored. Interrogation of the REpository for Molecular BRAin Neoplasia DaTa (REMBRANDT) revealed induction (DUSP4, DUSP6), repression (DUSP2, DUSP7-9), or mixed (DUSP1, DUSP5, DUSP10, DUSP15) DUSP transcription of select DUSPs in bulk tumor specimens...
August 18, 2017: Cancer Microenvironment: Official Journal of the International Cancer Microenvironment Society
https://www.readbyqxmd.com/read/28801478/phosphatases-and-solid-tumors-focus-on-glioblastoma-initiation-progression-and-recurrences
#14
REVIEW
Matthias Dedobbeleer, Estelle Willems, Stephen Freeman, Arnaud Lombard, Nicolas Goffart, Bernard Rogister
Phosphatases and cancer have been related for many years now, as these enzymes regulate key cellular functions, including cell survival, migration, differentiation and proliferation. Dysfunctions or mutations affecting these enzymes have been demonstrated to be key factors for oncogenesis. The aim of this review is to shed light on the role of four different phosphatases (PTEN, PP2A, CDC25 and DUSP1) in five different solid tumors (breast cancer, lung cancer, pancreatic cancer, prostate cancer and ovarian cancer), in order to better understand the most frequent and aggressive primary cancer of the central nervous system, glioblastoma...
August 11, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28743632/comparative-analysis-of-dual-specificity-protein-phosphatase-genes-1-2-and-5-in-response-to-immune-challenges-in-japanese-flounder-paralichthys-olivaceus
#15
Shuo Li, Gaixiang Hao, Jiafang Li, Weijiao Peng, Xuyun Geng, Jinsheng Sun
Dual-specificity MAP kinase (MAPK) phosphatases (DUSPs) are well-established negative modulators in regulating MAPK signaling in mammalian cells and tissues. Our previous studies have shown the involvement of DUSP6 in regulating innate immunity in Japanese flounder Paralichthys olivaceus. In order to gain a better understanding of the role of DUSPs in fish innate immunity, in the present study we identified and characterized three additional DUSP genes including DUSP1, 2 and 5 in P. olivaceus. The three Japanese flounder DUSP proteins share common domain structures composed of a conserved N-terminal Rhodanase/CDC25 domain and a C-terminal catalytic phosphatase domain, while they show only less than 26% sequence identities, indicating that they may have different substrate selectivity...
September 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28659609/macrophage-responses-to-lipopolysaccharide-are-modulated-by-a-feedback-loop-involving-prostaglandin-e2-dual-specificity-phosphatase-1-and-tristetraprolin
#16
Tina Tang, Thomas E Scambler, Tim Smallie, Helen E Cunliffe, Ewan A Ross, Dalya R Rosner, John D O'Neil, Andrew R Clark
In many different cell types, pro-inflammatory agonists induce the expression of cyclooxygenase 2 (COX-2), an enzyme that catalyzes rate-limiting steps in the conversion of arachidonic acid to a variety of lipid signaling molecules, including prostaglandin E2 (PGE2). PGE2 has key roles in many early inflammatory events, such as the changes of vascular function that promote or facilitate leukocyte recruitment to sites of inflammation. Depending on context, it also exerts many important anti-inflammatory effects, for example increasing the expression of the anti-inflammatory cytokine interleukin 10 (IL-10), and decreasing that of the pro-inflammatory cytokine tumor necrosis factor (TNF)...
June 28, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28626076/cardiac-fibroblast-transcriptome-analyses-support-a-role-for-interferogenic-profibrotic-and-inflammatory-genes-in-anti-ssa-ro-associated-congenital-heart-block
#17
Robert M Clancy, Androo J Markham, Tanisha Jackson, Sara E Rasmussen, Miroslav Blumenberg, Jill P Buyon
The signature lesion of SSA/Ro autoantibody-associated congenital heart block (CHB) is fibrosis and a macrophage infiltrate, supporting an experimental focus on cues influencing the fibroblast component. The transcriptomes of human fetal cardiac fibroblasts were analyzed using two complementary approaches. Cardiac injury conditions were simulated in vitro by incubating human fetal cardiac fibroblasts with supernatants from macrophages transfected with the SSA/Ro-associated noncoding Y ssRNA. The top 10 upregulated transcripts in the stimulated fibroblasts reflected a type I interferon (IFN) response [e...
September 1, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28624985/dusp1-and-kcnj2-mrna-upregulation-can-serve-as-a-biomarker-of-mechanical-asphyxia-induced-death-in-cardiac-tissue
#18
Yan Zeng, Li Tao, Jianlong Ma, Liujun Han, Yehui Lv, Pan Hui, Heng Zhang, Kaijun Ma, Bi Xiao, Qun Shi, Hongmei Xu, Long Chen
The incidence of death by asphyxia is second to the incidence of death by mechanical injury; however, death by mechanical asphyxia may be difficult to prove in court, particularly in cases in which corpses do not exhibit obvious signs of asphyxia. To identify a credible biomarker of asphyxia, we first examined the expression levels of 47,000 mRNAs in human cardiac tissue specimens from individuals who died of mechanical asphyxia and compared the expression levels with the levels of the corresponding mRNAs in specimens from individuals who died of craniocerebral injury using microarray...
June 17, 2017: International Journal of Legal Medicine
https://www.readbyqxmd.com/read/28618934/identification-of-curcumin-inhibited-extracellular-matrix-receptors-in-non-small-cell-lung-cancer-a549-cells-by-rna-sequencing
#19
Huiping Li, Hongjin Wu, Hongfang Zhang, Ying Li, Shuang Li, Qiang Hou, Shixiu Wu, Shuan-Ying Yang
Curcumin is a potent anti-cancer drug in several types of human cancers. Despite of several preclinical and clinical studies of curcumin, the precise mechanism of curcumin in cancer prevention has remained unclear. In our study, we for the first time investigated whole transcriptome alteration in A549 non-small cell lung cancer (NSCLC) cell lines after treatment with curcumin using RNA sequencing. We found that lots of genes and signaling pathways were significantly altered after curcumin treatment in A549 cells...
June 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28594854/identification-of-key-micrornas-and-genes-in-preeclampsia-by-bioinformatics-analysis
#20
Shouling Luo, Nannan Cao, Yao Tang, Weirong Gu
Preeclampsia is a leading cause of perinatal maternal-foetal mortality and morbidity. The aim of this study is to identify the key microRNAs and genes in preeclampsia and uncover their potential functions. We downloaded the miRNA expression profile of GSE84260 and the gene expression profile of GSE73374 from the Gene Expression Omnibus database. Differentially expressed miRNAs and genes were identified and compared to miRNA-target information from MiRWalk 2.0, and a total of 65 differentially expressed miRNAs (DEMIs), including 32 up-regulated miRNAs and 33 down-regulated miRNAs, and 91 differentially expressed genes (DEGs), including 83 up-regulated genes and 8 down-regulated genes, were identified...
2017: PloS One
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