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Protein phosphatase

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https://www.readbyqxmd.com/read/28340282/carfilzomib-induces-leukaemia-cell-apoptosis-via-inhibiting-elk1-kiaa1524-elk-1-cip2a-and-activating-pp2a-not-related-to-proteasome-inhibition
#1
Chun-Yu Liu, Feng-Shu Hsieh, Pei-Yi Chu, Wen-Chun Tsai, Chun-Teng Huang, Yuan-Bin Yu, Tzu-Ting Huang, Po-Shen Ko, Man-Hsin Hung, Wan-Lun Wang, Chung-Wai Shiau, Kuen-Feng Chen
Enhancing the tumour suppressive activity of protein phosphatase 2A (PP2A) has been suggested to be an anti-leukaemic strategy. KIAA1524 (also termed CIP2A), an oncoprotein inhibiting PP2A, is associated with disease progression in chronic myeloid leukaemia and may be prognostic in cytogenetically normal acute myeloid leukaemia. Here we demonstrated that the selective proteasome inhibitor, carfilzomib, induced apoptosis in sensitive primary leukaemia cells and in sensitive leukaemia cell lines, associated with KIAA1524 protein downregulation, increased PP2A activity and decreased p-Akt, but not with the proteasome inhibition effect of carfilzomib...
March 24, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28339485/chronic-parp-1-inhibition-reduces-carotid-vessel-remodeling-and-oxidative-damage-of-the-dorsal-hippocampus-in-spontaneously-hypertensive-rats
#2
Krisztian Eros, Klara Magyar, Laszlo Deres, Arpad Skazel, Adam Riba, Zoltan Vamos, Tamas Kalai, Ferenc Gallyas, Balazs Sumegi, Kalman Toth, Robert Halmosi
Vascular remodeling during chronic hypertension may impair the supply of tissues with oxygen, glucose and other compounds, potentially unleashing deleterious effects. In this study, we used Spontaneously Hypertensive Rats and normotensive Wistar-Kyoto rats with or without pharmacological inhibition of poly(ADP-ribose)polymerase-1 by an experimental compound L-2286, to evaluate carotid artery remodeling and consequent damage of neuronal tissue during hypertension. We observed elevated oxidative stress and profound thickening of the vascular wall with fibrotic tissue accumulation induced by elevated blood pressure...
2017: PloS One
https://www.readbyqxmd.com/read/28339072/hepatitis-b-virus-x-protein-increases-microrna%C3%A2-21-expression-and-accelerates-the-development-of-hepatoma-via-the-phosphatase-and-tensin-homolog-phosphoinositide-3%C3%A2-kinase-protein-kinase-b-signaling-pathway
#3
Zhouhua Hou, Jun Quan
Hepatitis B virus (HBV) X protein (HBx) is a key regulatory protein that is involved in HBV infection, replication and carcinogenesis of hepatocellular carcinoma (HCC). The aim of the present study was to investigate the role of HBx in the progression and metastasis of liver cancer cells and to determine the underlying molecular mechanism of HBx in metastatic liver cancer cells. HBx protein expression was detected by western blot analysis, and microRNA (miR)‑21 levels were determined by reverse transcription‑quantitative polymerase chain reaction in the highly metastatic MHCC‑97H low metastatic MHCC‑97L and SMMC‑7721 liver cancer cell lines...
March 23, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28339032/clc-7-ostm1-contribute-to-the-ability-of-tea-polyphenols-to-maintain-bone-homeostasis-in-c57bl-6-mice-protecting-against-fluorosis
#4
Bing-Yun Li, Yan-Hui Gao, Jun-Rui Pei, Yan-Mei Yang, Wei Zhang, Dian-Jun Sun
Epidemiological investigations indicate that certain ingredients in tea bricks can antagonize the adverse effects of fluoride. Tea polyphenols (TPs), the most bioactive ingredient in tea bricks, have been demonstrated to be potent bone-supporting agents. ClC‑7 is known to be crucial for osteoclast (OC) bone resorption. Thus, in this study, we investigated the potential protective effects of TPs against fluorosis using a mouse model and explored the underlying mechanisms with particular focus on ClC‑7...
March 22, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28339030/increased-phosphorylation-of-4e%C3%A2-binding-protein-1-predicts-poor-prognosis-for-patients-with-colorectal-cancer
#5
Yufeng Miao, Lige Chen, Cuifen Shi, Rengen Fan, Ping Chen, Hongqi Liu, Aihua Xia, Haixin Qian
As demonstrated in previous studies, the phosphorylated form of 4E‑binding protein 1 (p‑4E‑BP1) may be a suitable tumor biomarker. The aim of the current study was to examine the expression status of p‑4E‑BP1 in colorectal cancer (CRC), in order to determine its clinical significance. The present study enrolled 89 patients with CRC that had undergone radical resection. Paired tumor and adjacent normal tissues were evaluated using immunohistochemistry to detect the protein expression of p‑4E‑BP1 and phosphatase and tensin homolog (PTEN)...
March 22, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28339014/effects-of-remote-ischemic-post%C3%A2-conditioning-on-fracture-healing-in-rats
#6
Meng Zhou, Shibao Lu, Guowei Lu, Jiang Huang, Limin Liu, Shuai An, Zheng Li, Huiliang Shen
Remote ischemic post‑conditioning (RIPC) is an established method to activate the hypoxia‑inducible factor‑1α (HIF‑1α) pathway, which is involved in the impairment of fracture healing. However, the role of RIPC in fracture healing remains to be fully elucidated. In the present study, rats received fractures and were divided into two groups: Control and RIPC, in which hind limb occlusion was performed. Rats were sacrificed at 7, 14, 28 and 42 days subsequent to tibial fracture. Micro‑computed tomography was performed to measure healing of the bone tissue and biomechanical testing was used to test mechanical strength...
March 22, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28337797/standardized-sophora-pachycarpa-root-extract-enhances-osteogenic-differentiation-in-adipose-derived-human-mesenchymal-stem-cells
#7
Samaneh Mollazadeh, Vajiheh Neshati, Bibi Sedigheh Fazly Bazzaz, Mehrdad Iranshahi, Majid Mojarrad, Hojjat Naderi-Meshkin, Mohammad Amin Kerachian
Bone defect is an important topic in public health. Novel therapies are based on osteogenic induction by natural antiosteoporotic compounds including plant-derived estrogens. In the current study, the osteogenic potential of Sophora pachycarpa root extract (SPRE) was explored on human adipose-derived mesenchymal stem cells. Herein, adipose-derived mesenchymal stem cells were osteoinducted in the presence of increased concentrations of the extract for 21 days. Then, cell viability was evaluated by MTT assay, and the differentiated cells were stained by Alizarin Red S for calcium deposition and subjected to alkaline phosphatase (ALP) assay for enzymatic activity...
March 24, 2017: Phytotherapy Research: PTR
https://www.readbyqxmd.com/read/28337773/histone-h2b-monoubiquitination-regulates-salt-stress-induced-microtubule-depolymerization-in-arabidopsis
#8
Sa Zhou, Qiuhong Chen, Yuhui Sun, Yingzhang Li
Histone H2B monoubiquitination (H2Bub1) is recognized as a regulatory mechanism that controls a range of cellular processes. We previously showed that H2Bub1 was involved in responses to biotic stress in Arabidopsis. However, the molecular regulatory mechanisms of H2Bub1 in controlling responses to abiotic stress remain limited. Here, we report that HISTONE MONOUBIQUITINATION1 (HUB1) and HUB2 played important regulatory roles in response to salt stress. Phenotypic analysis revealed that H2Bub1 mutants confer decreased tolerance to salt stress...
March 24, 2017: Plant, Cell & Environment
https://www.readbyqxmd.com/read/28337542/%C3%AE-synuclein-binds-to-the-er-mitochondria-tethering-protein-vapb-to-disrupt-ca-2-homeostasis-and-mitochondrial-atp-production
#9
Sébastien Paillusson, Patricia Gomez-Suaga, Radu Stoica, Daniel Little, Paul Gissen, Michael J Devine, Wendy Noble, Diane P Hanger, Christopher C J Miller
α-Synuclein is strongly linked to Parkinson's disease but the molecular targets for its toxicity are not fully clear. However, many neuronal functions damaged in Parkinson's disease are regulated by signalling between the endoplasmic reticulum (ER) and mitochondria. This signalling involves close physical associations between the two organelles that are mediated by binding of the integral ER protein vesicle-associated membrane protein-associated protein B (VAPB) to the outer mitochondrial membrane protein, protein tyrosine phosphatase-interacting protein 51 (PTPIP51)...
March 23, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28337461/molecular-mechanism-for-the-regulation-of-microcystin-toxicity-to-protein-phosphatase-1-by-glutathione-conjugation-pathway
#10
Wansong Zong, Xiaoning Wang, Yonggang Du, Shuhan Zhang, Ying Zhang, Yue Teng
Glutathione (GSH) conjugation was an important pathway to regulate the toxicity of microcystins (MCs) targeted to protein phosphatases. To explore the specific molecular mechanism for GSH detoxification, two typical MC-GSHs (derived from MCLR and MCRR) were synthesized, prepared, and purified according to previous research. Then, the reduced inhibition effect for MC-GSHs on protein phosphatase 1 was verified by comparing with their original toxins. To further clarify the molecular mechanism for MC-GSHs detoxification, we evaluated the interactions between MCs/MC-GSHs and PP1 with the assistance of MOE molecule simulation...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28337284/hepatoprotective-effects-of-gentianella-turkestanerum-extracts-on-acute-liver-injury-induced-by-carbon-tetrachloride-in-mice
#11
Jianghua Yang, Dandan Zhu, Bowei Ju, Xiangying Jiang, Junping Hu
Objective: To investigate the contents of secoiridoid compounds (i.e. sweroside, swertiamarin and gentiopicrin) from Gentianella turkestanerum extracts, and the potential effects of G. turkestanerum extracts against carbon tetrachloride (CCl4) induced liver injury in mice. Methods: The contents of swertiamarin, gentiopicroside and sweroside from different G. turkestanerum extracts were determined with high performance liquid chromatography (HPLC). CCl4 was used to induce acute liver injury in mice. The serum aspartate amino transferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), total protein (TP), total bilirubin (TB), superoxide dismutase (SOD), malondialdehyde (MDA), glutathione transferase (GSH) and catalase (CAT) were measured...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28336172/curcuma-longa-linn-extract-and-curcumin-protect-cyp-2e1-enzymatic-activity-against-mercuric-chloride-induced-hepatotoxicity-and-oxidative-stress-a-protective-approach
#12
Deepmala Joshi, Deepak Kumar Mittal, Sangeeta Shukla, Sunil Kumar Srivastav, Vaibhav A Dixit
The present investigation has been conducted to evaluate the therapeutic potential of Curcuma longa (200mgkg(-1), po) and curcumin (80mgkg(-1), po) for their hepatoprotective efficacy against mercuric chloride (HgCl2: 12μmolkg(-1), ip; once only) hepatotoxicity. The HgCl2 administration altered various biochemical parameters, including transaminases, alkaline phosphatase, lactate dehydrogenase, bilirubin, gamma-glutamyl transferase, triglycerides and cholesterol contents with a concomitant decline in protein and albumin concentration in serum which were restored towards control by therapy of Curcuma longa or curcumin...
March 20, 2017: Experimental and Toxicologic Pathology: Official Journal of the Gesellschaft Für Toxikologische Pathologie
https://www.readbyqxmd.com/read/28335251/nanostructured-tio%C3%A2-surfaces-promote-human-bone-marrow-mesenchymal-stem-cells-differentiation-to-osteoblasts
#13
Marco Vercellino, Gabriele Ceccarelli, Francesco Cristofaro, Martina Balli, Federico Bertoglio, Gianna Bruni, Laura Benedetti, Maria Antonietta Avanzini, Marcello Imbriani, Livia Visai
Micro- and nano-patterning/modification are emerging strategies to improve surfaces properties that may influence critically cells adherence and differentiation. Aim of this work was to study the in vitro biological reactivity of human bone marrow mesenchymal stem cells (hBMSCs) to a nanostructured titanium dioxide (TiO₂) surface in comparison to a coverglass (Glass) in two different culture conditions: with (osteogenic medium (OM)) and without (proliferative medium (PM)) osteogenic factors. To evaluate cell adhesion, hBMSCs phosphorylated focal adhesion kinase (pFAK) foci were analyzed by confocal laser scanning microscopy (CLSM) at 24 h: the TiO₂ surface showed a higher number of pFAK foci with respect to Glass...
June 24, 2016: Nanomaterials
https://www.readbyqxmd.com/read/28334935/genome-wide-association-study-of-iron-traits-and-relation-to-diabetes-in-the-hispanic-community-health-study-study-of-latinos-hchs-sol-potential-genomic-intersection-of-iron-and-glucose-regulation
#14
Laura M Raffield, Tin Louie, Tamar Sofer, Deepti Jain, Eli Ipp, Kent D Taylor, George J Papanicolaou, Larissa Avilés-Santa, Leslie A Lange, Cathy C Laurie, Matthew P Conomos, Timothy A Thornton, Yii-Der Ida Chen, Qibin Qi, Scott Cotler, Bharat Thyagarajan, Neil Schneiderman, Jerome I Rotter, Alex P Reiner, Henry J Lin
Genetic variants contribute to normal variation of iron-related traits and may also cause clinical syndromes of iron deficiency or excess. Iron overload and deficiency can adversely affect human health. For example, elevated iron storage is associated with increased diabetes risk, although mechanisms are still being investigated. We conducted the first genome-wide association study (GWAS) of serum iron, total iron binding capacity (TIBC), transferrin saturation, and ferritin in a Hispanic/Latino cohort, the Hispanic Community Health Study/Study of Latinos (HCHS/SOL; >12,000 participants) and also assessed the generalization of previously known loci to this population...
March 7, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28334808/downregulation-of-pathways-implicated-in-liver-inflammation-and-tumorigenesis-of-glycogen-storage-disease-type-ia-mice-receiving-gene-therapy
#15
Goo-Young Kim, Joon Hyun Kwon, Jun-Ho Cho, Lisa Zhang, Brian C Mansfield, Janice Y Chou
Glycogen storage disease type Ia (GSD-Ia) is characterized by impaired glucose homeostasis and long-term risks of hepatocellular adenoma (HCA) and carcinoma (HCC). We have shown that the non-tumor-bearing (NT), recombinant adeno-associated virus (rAAV) vector-treated GSD-Ia mice (AAV-NT mice) expressing a wide range (0.9-63%) of normal hepatic glucose-6-phosphatase-α activity maintain glucose homeostasis and display physiologic features mimicking animals living under calorie restriction (CR). We now show that in AAV-NT mice, the signaling pathways of the CR mediators, AMP-activated protein kinase (AMPK) and sirtuin-1 are activated...
March 13, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28334609/basolateral-to-central-amygdala-neural-circuits-for-appetitive-behaviors
#16
Joshua Kim, Xiangyu Zhang, Shruti Muralidhar, Sarah A LeBlanc, Susumu Tonegawa
Basolateral amygdala (BLA) principal cells are capable of driving and antagonizing behaviors of opposing valence. BLA neurons project to the central amygdala (CeA), which also participates in negative and positive behaviors. However, the CeA has primarily been studied as the site for negative behaviors, and the causal role for CeA circuits underlying appetitive behaviors is poorly understood. Here, we identify several genetically distinct populations of CeA neurons that mediate appetitive behaviors and dissect the BLA-to-CeA circuit for appetitive behaviors...
March 22, 2017: Neuron
https://www.readbyqxmd.com/read/28334048/hepatoprotective-effect-of-sitagliptin-against-methotrexate-induced-liver-toxicity
#17
Hany M Abo-Haded, Mohamed A Elkablawy, Zeyad Al-Johani, Osama Al-Ahmadi, Dina S El-Agamy
Sitagliptin is selective dipeptidyl peptidase-4 inhibitor (DPP4-I), used clinically as a new oral anti-diabetic agent. This study explored the underlying mechanisms of the hepatoprotective role of sitagliptin pretreatment against methotrexate (MTX) induced hepatotoxicity in mice. Forty mice were divided into four groups (10 mice each); control, MTX, and two sitagliptin groups (pretreated with sitagliptin 10 and 20 mg/kg/day, respectively) for five consecutive days prior to MTX injection. Results showed that MTX induced marked hepatic injury in the form of cloudy swelling, hydropic degeneration, apoptosis and focal necrosis in all hepatic zones...
2017: PloS One
https://www.readbyqxmd.com/read/28333146/cdc25a-phosphatase-a-key-cell-cycle-protein-that-regulates-neuron-death-in-disease-and-development
#18
Subhas Chandra Biswas, Priyankar Sanphui, Nandini Chatterjee, Stav Kemeny, Lloyd A Greene
No abstract text is available yet for this article.
March 23, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28333141/npas2-promotes-cell-survival-of-hepatocellular-carcinoma-by-transactivating-cdc25a
#19
Peng Yuan, Jibin Li, Feng Zhou, Qichao Huang, Jiansheng Zhang, Xu Guo, Zhuomin Lyu, Hongxin Zhang, Jinliang Xing
Emerging evidences show that disruption of the circadian rhythm is associated with tumor initiation and progression. Neuronal PAS domain protein 2 (NPAS2), one of the core circadian molecules, has been proved to be a potential prognostic biomarker in colorectal and breast cancers. However, to date, the potential functional roles and molecular mechanisms by which NPAS2 affects cancer cell survival are greatly unclear, especially in hepatocellular carcinoma (HCC). We first investigated the expression of NPAS2 and its clinical significance in HCC...
March 23, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28332354/cyclized-oligopeptide-targeting-lrp5-6-dkk1-interaction-reduces-the-growth-of-tumor-burden-in-a-multiple-myeloma-mouse-model
#20
Bo Mi Park, Eun Jin Kim, Hee Jin Nam, Dongdong Zhang, Chu Hyun Bae, Myeongmo Kang, Heeyoun Kim, Weontae Lee, Bjarne Bogen, Sung Kil Lim
PURPOSE: Dickkopf 1 (DKK1) has been extensively investigated in mouse models of multiple myeloma, which results in osteolytic bone lesions. Elevated DKK1 levels in bone marrow plasma and serum inhibit the differentiation of osteoblast precursors. Present pharmaceutical approaches to target bone lesions are limited to antiresorptive agents. In this study, we developed a cyclized oligopeptide against DKK1-low density lipoprotein receptor-related protein (LRP) 5/6 interaction and tested the effects of the oligopeptide on tumor burden...
May 2017: Yonsei Medical Journal
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