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Protein phosphatase 2a

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https://www.readbyqxmd.com/read/28820083/threonine-deficiency-decreased-intestinal-immunity-and-aggravated-inflammation-associated-with-nf-%C3%AE%C2%BAb-and-target-of-rapamycin-signalling-pathways-in-juvenile-grass-carp-ctenopharyngodon-idella-after-infection-with-aeromonas-hydrophila
#1
Yu-Wen Dong, Wei-Dan Jiang, Yang Liu, Pei Wu, Jun Jiang, Sheng-Yao Kuang, Ling Tang, Wu-Neng Tang, Yong-An Zhang, Xiao-Qiu Zhou, Lin Feng
This study aimed to investigate the impacts of dietary threonine on intestinal immunity and inflammation in juvenile grass carp. Six iso-nitrogenous semi-purified diets containing graded levels of threonine (3·99-21·66 g threonine/kg) were formulated and fed to fishes for 8 weeks, and then challenged with Aeromonas hydrophila for 14 d. Results showed that, compared with optimum threonine supplementation, threonine deficiency (1) decreased the ability of fish against enteritis, intestinal lysozyme activities (except in the distal intestine), acid phosphatase activities, complement 3 (C3) and C4 contents and IgM contents (except in the proximal intestine (PI)), and it down-regulated the transcript abundances of liver-expressed antimicrobial peptide (LEAP)-2A, LEAP-2B, hepcidin, IgZ, IgM and β-defensin1 (except in the PI) (P<0·05); (2) could up-regulate intestinal pro-inflammatory cytokines TNF-α, IL-1β, IL-6, IL-8 and IL-17D mRNA levels partly related to NF-κB signalling; (3) could down-regulate intestinal anti-inflammatory cytokine transforming growth factor (TGF)-β1, TGF-β2, IL-4/13A (not IL-4/13B) and IL-10 mRNA levels partly by target of rapamycin signalling...
July 2017: British Journal of Nutrition
https://www.readbyqxmd.com/read/28819544/hypoxia-downregulates-mapk-erk-but-not-stat3-signaling-in-ros-dependent-and-hif-1-independent-manners-in-mouse-embryonic-stem-cells
#2
Jan Kučera, Julie Netušilová, Stanislava Sladeček, Martina Lánová, Ondřej Vašíček, Kateřina Štefková, Jarmila Navrátilová, Lukáš Kubala, Jiří Pacherník
Hypoxia is involved in the regulation of stem cell fate, and hypoxia-inducible factor 1 (HIF-1) is the master regulator of hypoxic response. Here, we focus on the effect of hypoxia on intracellular signaling pathways responsible for mouse embryonic stem (ES) cell maintenance. We employed wild-type and HIF-1α-deficient ES cells to investigate hypoxic response in the ERK, Akt, and STAT3 pathways. Cultivation in 1% O2 for 24 h resulted in the strong dephosphorylation of ERK and its upstream kinases and to a lesser extent of Akt in an HIF-1-independent manner, while STAT3 phosphorylation remained unaffected...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28813646/antihelminthic-drug-niclosamide-inhibits-cip2a-and-reactivates-tumor-suppressor-protein-phosphatase-2a-in-non-small-cell-lung-cancer-cells
#3
Myeong-Ok Kim, Min Ho Choe, Yi Na Yoon, Jiyeon Ahn, Minjin Yoo, Kwan-Young Jung, Sungkwan An, Sang-Gu Hwang, Jeong Su Oh, Jae-Sung Kim
Protein phosphatase 2A (PP2A) is a critical tumor suppressor complex responsible for the inactivation of various oncogenes. Recently, PP2A reactivation has emerged as an anticancer strategy. Cancerous inhibitor of protein phosphatase 2A (CIP2A), an endogenous inhibitor of PP2A, is upregulated in many cancer cells, including non-small cell lung cancer (NSCLC) cells. We demonstrated that the antihelminthic drug niclosamide inhibited the expression of CIP2A and reactivated the tumor suppressor PP2A in NSCLC cells...
August 13, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28807678/metformin-lowers-%C3%AE-synuclein-phosphorylation-and-upregulates-neurotrophic-factor-in-the-mptp-mouse-model-of-parkinson-s-disease
#4
Nikita Katila, Sunil Bhurtel, Sina Shadfar, Sunil Srivastav, Sabita Neupane, Uttam Ojha, Gil-Saeng Jeong, Dong-Young Choi
In spite of the massive research for the identification of neurorestorative or neuroprotective intervention for curing Parkinson's disease (PD), there is still lack of clinically proven neuroprotective agents. Metformin, a common anti-hyperglycemic drug has been known to possess neuroprotective properties. However, specific mechanisms by which metformin protects neurons from 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) neurotoxicity remain to be elucidated. In this study, we assessed the neuroprotective effects of metformin in the subchronic MPTP model of PD, and explored its feasible mechanisms for neuroprotection...
August 11, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28807153/c1q-tumor-necrosis-factor-related-protein-3-enhances-the-contractility-of-cardiomyocyte-by-increasing-calcium-sensitivity
#5
Cheng-Lin Zhang, Zheng-Ju Chen, Han Feng, Qian Zhao, Yang-Po Cao, Li Li, Jin-Yu Wang, Yan Zhang, Li-Ling Wu
C1q/tumor necrosis factor-related protein-3 (CTRP3) is an adipokine that protects against myocardial infarction-induced cardiac dysfunction through its pro-angiogenic, anti-apoptotic, and anti-fibrotic effects. However, whether CTRP3 can directly affect the systolic and diastolic function of cardiomyocytes remains unknown. Adult rat cardiomyocytes were isolated and loaded with Fura-2AM. The contraction and Ca(2+) transient data was collected and analyzed by IonOptix system. 1 and 2μg/ml CTRP3 significantly increased the contraction of cardiomyocytes...
September 2017: Cell Calcium
https://www.readbyqxmd.com/read/28797448/dual-peptide-mediated-targeted-delivery-of-bioactive-sirnas-to-oral-cancer-cells-in-vivo
#6
Angela A Alexander-Bryant, Haiwen Zhang, Christopher C Attaway, William Pugh, Laurence Eggart, Robert M Sansevere, Lourdes M Andino, Lu Dinh, Liliana P Cantini, Andrew Jakymiw
OBJECTIVES: Despite significant advances in cancer treatment, the prognosis for oral cancer remains poor in comparison to other cancer types, including breast, skin, and prostate. As a result, more effective therapeutic modalities are needed for the treatment of oral cancer. Consequently, in the present study, we examined the feasibility of using a dual peptide carrier approach, combining an epidermal growth factor receptor (EGFR)-targeting peptide with an endosome-disruptive peptide, to mediate targeted delivery of small interfering RNAs (siRNAs) into EGFR-overexpressing oral cancer cells and induce silencing of the targeted oncogene, cancerous inhibitor of protein phosphatase 2A (CIP2A)...
September 2017: Oral Oncology
https://www.readbyqxmd.com/read/28777780/coupling-tor-to-the-cell-cycle-by-the-greatwall-endosulfine-pp2a-b55-pathway
#7
REVIEW
Livia Pérez-Hidalgo, Sergio Moreno
Cell growth and division are two processes tightly coupled in proliferating cells. While Target of Rapamycin (TOR) is the master regulator of growth, the cell cycle is dictated by the activity of the cyclin-dependent kinases (CDKs). A long-standing question in cell biology is how these processes may be connected. Recent work has highlighted that regulating the phosphatases that revert CDK phosphorylations is as important as regulating the CDKs for cell cycle progression. At mitosis, maintaining a low level of protein phosphatase 2A (PP2A)-B55 activity is essential for CDK substrates to achieve the correct level of phosphorylation...
August 4, 2017: Biomolecules
https://www.readbyqxmd.com/read/28770955/the-regulatory-role-of-dopamine-receptor-d1-on-pp2a-via-sumo-1-modification
#8
C-Q Yu, L-Q Yin, Z-T Tu, D-W Liu, W-P Luo
OBJECTIVE: Renal dopamine receptor D1 played a critical role in the regulation of body blood pressure. Under hypertension, over-phosphorylation of D1 receptor impaired its function. G protein kinase 4 (GRK4) and protein phosphatase 2A (PP2A) exerted the effect to phosphorylate and de-phosphorylate D1 receptor. A current study revealed that the inhibition of GRK4 cannot normalize the phosphorylation level of D1 receptor. Meanwhile, the PP2A was activated under hypertension, indicating abnormal de-phosphorylation function of D1 receptor, the reason for which remains unknown...
July 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28769011/chlorpheniramine-increases-paracellular-permeability-to-marker-fluorescein-lucifer-yellow-mediated-by-internalization-of-occludin-in-murine-colonic-epithelial-cells
#9
Aya Manabe, Chisa Furukawa, Satoshi Endo, Kana Marunaka, Tsubasa Nishiyama, Naoko Fujii, Yoshiaki Tabuchi, Toshiyuki Matsunaga, Akira Ikari
Ions, small molecules, and drugs are absorbed in the intestinal epithelium mediated by transcellular and paracellular pathways. The function of various transporters expressing in the apical and basolateral membranes of intestinal epithelial cells has been well characterized. In contrast, claudins and occludin, components of the tight junctions (TJs), determine the paracellular permeability to ions and low molecular weight compounds, but the properties for permeability has not been clarified in detail. In the present study, we examined the effects of anti-histamine drugs, chlorpheniramine and diphenhydramine, on transepithelial electrical resistance (TER) and permeability to lucifer yellow (LY), a marker of paracellular permeability, using murine colonic MCE301 cells...
2017: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28765008/microcystin-leucine-arginine-exhibits-immunomodulatory-roles-in-testicular-cells-resulting-in-orchitis
#10
Yabing Chen, Jing Wang, Qin Zhang, Zou Xiang, Dongmei Li, Xiaodong Han
Microcystin-leucine arginine (MC-LR) causes testicular inflammation and hinders spermatogenesis. However, the molecular mechanisms underlying the immune responses to MC-LR in the testis have not been elucidated in detail. In this study, we show that MC-LR induced immune responses in Sertoli cells (SC), germ cells (GC), and Leydig cells (LC) via activating phosphatidylinositol 3-kinase (PI3K)/AKT/nuclear factor kappa B (NF-κB), resulting in the production of pro-inflammatory cytokines and chemokines including tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), and chemokine (C-X-C motif) ligand 10 (CXCL10)...
July 29, 2017: Environmental Pollution
https://www.readbyqxmd.com/read/28747544/activation-of-cancerous-inhibitor-of-pp2a-cip2a-contributes-to-lapatinib-resistance-through-induction-of-cip2a-akt-feedback-loop-in-erbb2-positive-breast-cancer-cells
#11
Ming Zhao, Erin W Howard, Amanda B Parris, Zhiying Guo, Qingxia Zhao, Zhikun Ma, Ying Xing, Bolin Liu, Susan M Edgerton, Ann D Thor, Xiaohe Yang
Lapatinib, a small molecule ErbB2/EGFR inhibitor, is FDA-approved for the treatment of metastatic ErbB2-overexpressing breast cancer; however, lapatinib resistance is an emerging clinical challenge. Understanding the molecular mechanisms of lapatinib-mediated anti-cancer activities and identifying relevant resistance factors are of pivotal significance. Cancerous inhibitor of protein phosphatase 2A (CIP2A) is a recently identified oncoprotein that is overexpressed in breast cancer. Our study investigated the role of CIP2A in the anti-cancer efficacy of lapatinib in ErbB2-overexpressing breast cancer cells...
July 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/28744751/functional-importance-of-pp2a-regulatory-subunit-loss-in-breast-cancer
#12
Lauren F Watt, Nikita Panicker, Abdul Mannan, Ben Copeland, Richard G S Kahl, Matthew D Dun, Barbara Young, Severine Roselli, Nicole M Verrills
PURPOSE: Protein phosphatase 2A (PP2A) is a family of serine/threonine phosphatases that regulate multiple cellular signalling pathways involved in proliferation, survival and apoptosis. PP2A inhibition occurs in many cancers and is considered a tumour suppressor. Deletion/downregulation of PP2A genes has been observed in breast tumours, but the functional role of PP2A subunit loss in breast cancer has not been investigated. METHODS: PP2A subunit expression was examined by immunohistochemistry in human breast tumours, and by qPCR and immunoblotting in breast cancer cell lines...
July 25, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28743803/the-glucocorticoid-angptl4-ceramide-axis-induces-insulin-resistance-through-pp2a-and-pkc%C3%AE
#13
Tzu-Chieh Chen, Daniel I Benjamin, Taiyi Kuo, Rebecca A Lee, Mei-Lan Li, Darryl J Mar, Damian E Costello, Daniel K Nomura, Jen-Chywan Wang
Chronic glucocorticoid exposure is associated with the development of insulin resistance. We showed that glucocorticoid-induced insulin resistance was attenuated upon ablation of Angptl4, a glucocorticoid target gene encoding the secreted protein angiopoietin-like 4, which mediates glucocorticoid-induced lipolysis in white adipose tissue. Through metabolomic profiling, we revealed that glucocorticoid treatment increased hepatic ceramide concentrations by inducing enzymes in the ceramide synthetic pathway in an Angptl4-dependent manner...
July 25, 2017: Science Signaling
https://www.readbyqxmd.com/read/28741704/methylation-of-protein-phosphatase-2a-influence-of-regulators-and-environmental-stress-factors
#14
Maria T Creighton, Anna Kolton, Amr R A Kataya, Jodi Maple-Grødem, Irina O Averkina, Behzad Heidari, Cathrine Lillo
Protein phosphatase 2A catalytic subunit (PP2A-C) has a terminal leucine subjected to methylation, a regulatory mechanism conserved from yeast to mammals and plants. Two enzymes, LCMT1 and PME1, methylate and demethylate PP2A-C, respectively. The physiological importance of these posttranslational modifications is still enigmatic. We investigated these processes in Arabidopsis thaliana by mutant phenotyping, global expression analysis, and by monitoring methylation status of PP2A-C under different environmental conditions...
July 25, 2017: Plant, Cell & Environment
https://www.readbyqxmd.com/read/28736280/the-serine-threonine-protein-phosphatase-2a-controls-autoimmunity
#15
Amir Sharabi, Isaac R Kasper, George C Tsokos
Protein phosphatase 2A (PP2A) is the first Ser/Thr phosphatase recognized to contribute to human and murine lupus immunopathology. PP2A expression in SLE is controlled both epigenetically and genetically, and it is increased in patients with SLE, which contributes to decreased IL-2 production, decreased CD3ζ and increased FcRγ expression on the surface of T cells, increased CREMα expression, hypomethylation of genes associated with SLE pathogenesis, and increased IL-17 production. B regulatory subunit of PP2A regulates IL-2 deprivation-induced T cell death and is decreased in SLE patients...
July 20, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28720534/tgf-%C3%AE-signaling-regulates-p-akt-levels-via-pp2a-during-diapause-entry-in-the-cotton-bollworm-helicoverpa-armigera
#16
Hai-Yin Li, Tao Wang, Yong-Pan Yang, Shao-Lei Geng, Wei-Hua Xu
Akt, which is a key kinase in the insulin signaling pathway, plays important roles in glucose metabolism, cell proliferation, transcription and cell migration. Our previous studies indicated that low insulin levels and high p-Akt levels are present in diapause-destined individuals. Here, we show that PI3K, which is upstream of Akt, is low in diapause-destined pupal brains but high in p-Akt levels, implying that p-Akt is modified by factors other than the insulin signaling pathway. Protein phosphatase 2A (PP2A), which is a key regulator in the TGF-β signaling pathway, can directly bind to and dephosphorylate Akt...
August 2017: Insect Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28720530/downregulation-of-protein-phosphatase-2a-by-apolipoprotein-e-implications-for-alzheimer-s-disease
#17
Veena Theendakara, Dale E Bredesen, Rammohan V Rao
The apolipoprotein E ε4 allele is the single most important genetic risk factor associated with Alzheimer's disease (AD). Tau phosphorylation and hyperphosphorylation is an underlying feature of AD and is regulated by specific kinases and phosphatases. Among phosphatases, protein phosphatase 2A (PP2A) is the principal tau dephosphorylating enzyme in the brain. Several abnormalities of PP2A have been reported in AD, including among others decreased protein levels of PP2A, decreased mRNA and protein levels of the catalytic subunit PP2AC and variable regulatory B subunits and reduced methylation of the catalytic subunit, all of which results in disruption of the PP2A phosphatase activity...
July 15, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/28711506/sodium-selenate-activated-wnt-%C3%AE-catenin-signaling-and-repressed-amyloid-%C3%AE-formation-in-a-triple-transgenic-mouse-model-of-alzheimer-s-disease
#18
Na Jin, Huazhang Zhu, Xiao Liang, Wei Huang, Qingguo Xie, Peng Xiao, Jiazuan Ni, Qiong Liu
Accumulating evidences show that selenium dietary intake is inversely associated with the mortality of Alzheimer's disease (AD). Sodium selenate has been reported to reduce neurofibrillary tangles (NFT) in the tauopathic mouse models, but its effects on the Wnt/β-catenin signaling pathway and APP processing remain unknown during AD formation. In this paper, triple transgenic AD mice (3×Tg-AD) had been treated with sodium selenate in drinking water for 10month before the detection of hippocampal pathology...
July 13, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28700947/acute-dietary-restriction-acts-via-tor-pp2a-and-myc-signaling-to-boost-innate-immunity-in-drosophila
#19
Jung-Eun Lee, Morsi Rayyan, Allison Liao, Isaac Edery, Scott D Pletcher
Dietary restriction promotes health and longevity across taxa through mechanisms that are largely unknown. Here, we show that acute yeast restriction significantly improves the ability of adult female Drosophila melanogaster to resist pathogenic bacterial infections through an immune pathway involving downregulation of target of rapamycin (TOR) signaling, which stabilizes the transcription factor Myc by increasing the steady-state level of its phosphorylated forms through decreased activity of protein phosphatase 2A...
July 11, 2017: Cell Reports
https://www.readbyqxmd.com/read/28700668/conditional-cell-reprogramming-involves-non-canonical-%C3%AE-catenin-activation-and-mtor-mediated-inactivation-of-akt
#20
Frank A Suprynowicz, Christopher M Kamonjoh, Ewa Krawczyk, Seema Agarwal, Anton Wellstein, Fadeke A Agboke, Sujata Choudhury, Xuefeng Liu, Richard Schlegel
The combination of irradiated fibroblast feeder cells and Rho kinase inhibitor, Y-267362, converts primary epithelial cells growing in vitro into an undifferentiated adult stem cell-like state that is characterized by long-term proliferation. This cell culture method also maintains the proliferation of adult epithelial stem cells from various tissues. Both primary and adult stem cells retain their tissue-specific differentiation potential upon removal of the culture conditions. Due to the ability to modulate the proliferation and differentiation of the cells, this method is referred to as conditional reprogramming and it is increasingly being used in studies of tumor heterogeneity, personalized medicine and regenerative medicine...
2017: PloS One
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