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https://www.readbyqxmd.com/read/28807827/the-endotoxemia-cardiac-dysfunction-is-attenuated-by-ampk-mtor-signaling-pathway-regulating-autophagy
#1
Jie Zhang, Peng Zhao, Nanhu Quan, Lin Wang, Xu Chen, Courtney Cates, Thomas Rousselle, Ji Li
AMP-activated protein kinase (AMPK), an enzyme that plays a role in cellular energy homeostasis, modulates myocardial signaling in the heart. Myocardial dysfunction is a common complication of sepsis. Autophagy is involved in the aging related cardiac dysfunction. However, the role of AMPK in sepsis-induced cardiotoxicity has yet to be clarified, especially in aging. In this study, we explored the role of AMPK on lipopolysaccharide (LPS)-induced myocardial dysfunction and elucidated the potential mechanisms of AMPK/mTOR pathway against autophagy in young and aged mice...
August 11, 2017: Biochemical and Biophysical Research Communications
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
#2
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/28805158/pp2a-regulatory-subunit-b55%C3%AE-is-a-gatekeeper-of-osteoblast-maturation-and-lineage-maintenance
#3
Anastassia Serguienko, Robert Hanes, Iwona Grad, Meng-Yu Wang, Ola Myklebost, Else Munthe
Bone marrow mesenchymal stem cells (BM MSCs) mediate skeletal remodeling by differentiating into osteoblasts. However, this remodeling is impaired with aging as well as following long-term glucocorticoid treatment, resulting in osteoporosis. Here we report a novel factor of osteoblast differentiation - PP2A regulatory subunit B55γ. We show that B55γ is induced by glucocorticoid receptor (GR) in human primary BM MSCs during differentiation to osteoblast, but not to adipocytes, and is required for osteoblast morphogenesis and mineralization...
August 12, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/28801478/phosphatases-and-solid-tumors-focus-on-glioblastoma-initiation-progression-and-recurrences
#4
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/28790387/gsk3%C3%AE-and-erk-regulate-the-expression-of-78%C3%A2-kda-sg2na-and-ectopic-modulation-of-its-level-affects-phases-of-cell-cycle
#5
Shweta Pandey, Indrani Talukdar, Buddhi P Jain, Shyamal K Goswami
Striatin and SG2NA are essential constituents of the multi-protein STRIPAK assembly harbouring protein phosphatase PP2A and several kinases. SG2NA has several isoforms generated by mRNA splicing and editing. While the expression of striatin is largely restricted to the striatum in brain, that of SG2NAs is ubiquitous. In NIH3T3 cells, only the 78 kDa isoform is expressed. When cells enter into the S phase, the level of SG2NA increases; reaches maximum at the G2/M phase and declines thereafter. Downregulation of SG2NA extends G1 phase and its overexpression extends G2...
August 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28777780/coupling-tor-to-the-cell-cycle-by-the-greatwall-endosulfine-pp2a-b55-pathway
#6
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
#7
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/28765008/microcystin-leucine-arginine-exhibits-immunomodulatory-roles-in-testicular-cells-resulting-in-orchitis
#8
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/28760745/a-pp2a-mediated-feedback-mechanism-controls-ca-2-dependent-no-synthesis-under-physiological-oxygen
#9
Thomas P Keeley, Richard C M Siow, Ron Jacob, Giovanni E Mann
Intracellular O2 is a key regulator of NO signaling, yet most in vitro studies are conducted in atmospheric O2 levels, hyperoxic with respect to the physiologic milieu. We investigated NO signaling in endothelial cells cultured in physiologic (5%) O2 and stimulated with histamine or shear stress. Culture of cells in 5% O2 (>5 d) decreased histamine- but not shear stress-stimulated endothelial (e)NOS activity. Unlike cells adapted to a hypoxic environment (1% O2), those cultured in 5% O2 still mobilized sufficient Ca(2+) to activate AMPK...
July 31, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28751710/aurora-b-kinase-pathway-controls-the-lateral-to-end-on-conversion-of-kinetochore-microtubule-attachments-in-human-cells
#10
Roshan L Shrestha, Duccio Conti, Naoka Tamura, Dominique Braun, Revathy A Ramalingam, Konstanty Cieslinski, Jonas Ries, Viji M Draviam
Human chromosomes are captured along microtubule walls (lateral attachment) and then tethered to microtubule-ends (end-on attachment) through a multi-step end-on conversion process. Upstream regulators that orchestrate this remarkable change in the plane of kinetochore-microtubule attachment in human cells are not known. By tracking kinetochore movements and using kinetochore markers specific to attachment status, we reveal a spatially defined role for Aurora-B kinase in retarding the end-on conversion process...
July 28, 2017: Nature Communications
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/28727495/localization-of-pp2a-b56-to-centromeres-in-drosophila
#16
Emil Peter Thrane Hertz, Jakob Nilsson
Protection of chromosome cohesion through Shugoshin-dependent recruitment of the PP2A-B56 phosphatase to the pericentromeric region has become a cornerstone of the chromosome segregation model in eukaryotes. Shugoshin is essential for meiotic chromosome segregation in all tested eukaryotes but only found to be essential for mitotic chromosome segregation in vertebrates. Nishiyama and colleagues have now found that the protein Dalmatian, an ortholog of the vertebrate cohesion regulator Sororin, performs the function of Shugoshin in Drosophila melanogaster by recruiting PP2A-B56 to the pericentromeric region supporting an unified model of mitotic chromosome segregation in the animal kingdom...
July 19, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28723647/set-contributes-to-the-epithelial-mesenchymal-transition-of-pancreatic-cancer
#17
Hardik R Mody, Sau Wai Hung, Kineta Naidu, Haesung Lee, Caitlin A Gilbert, Toan Thanh Hoang, Rakesh K Pathak, Radhika Manoharan, Shanmugam Muruganandan, Rajgopal Govindarajan
Pancreatic cancer has a devastating prognosis due to 80-90% of diagnostic cases occurring when metastasis has already presented. Activation of the epithelial-mesenchymal transition (EMT) is a prerequisite for metastasis because it allows for the dissemination of tumor cells to blood stream and secondary organs. Here, we sought to determine the role of SET oncoprotein, an endogenous inhibitor of PP2A, in EMT and pancreatic tumor progression. Among the two major isoforms of SET (isoform 1 and isoform 2), higher protein levels of SET isoform 2 were identified in aggressive pancreatic cancer cell lines...
July 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28723235/localization-of-pp2a-b56-to-centromeres-in-drosophila
#18
Emil Hertz, Thrane Hertz, Jakob Nilsson
No abstract text is available yet for this article.
July 19, 2017: Cell Cycle
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
#19
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
#20
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
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