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https://www.readbyqxmd.com/read/29331388/e4bp4-inhibits-angii-induced-apoptosis-in-h9c2-cardiomyoblasts-by-activating-the-pi3k-akt-pathway-and-promoting-calcium-uptake
#1
Bih-Cheng Chen, Marthandam Asokan Shibu, Chia-Hua Kuo, Chia-Yao Shen, Shu Nu Chang-Lee, Chao-Hung Lai, Ray-Jade Chen, Chun-Hsu Yao, Vijaya Padma Viswanadha, Jian-Shen Liu, Wei-Kung Chen, Chih-Yang Huang
The bZIP transcription factor E4BP4 is a survival factor that is known to be elevated in diseased heart and promote cell survival. In this study the role of E4BP4 on angiotensin-II (AngII)-induced apoptosis has been examined in in vitro cell model. H9c2 cardiomyoblast cells that overexpressed E4BP4 were exposed to AngII to observe the cardio-protective effects of E4BP4 on hypertension related apoptosis. The results from TUNEL assays revealed that E4BP4 significantly attenuated AngII-induced apoptosis. Further analysis by Western blot and RT-PCR showed that E4BP4 inhibited AngII-induced IGF-II mRNA expression and cleavage of caspase-3 through the PI3K-Akt pathway...
January 10, 2018: Experimental Cell Research
https://www.readbyqxmd.com/read/29330298/stemness-is-enhanced-in-gastric-cancer-by-a-set-pp2a-e2f1-axis
#2
Shuhei Enjoji, Ryotaro Yabe, Shunya Tsuji, Kazuhiro Yoshimura, Hideyoshi Kawasaki, Masashi Sakurai, Yusuke Sakai, Hiroko Takenouchi, Shigefumi Yoshino, Shoichi Hazama, Hiroaki Nagano, Hiroko Oshima, Masanobu Oshima, Michael P Vitek, Tetsuya Matsuura, Yoshitaka Hippo, Tatsuya Usui, Takashi Ohama, Koichi Sato
Gastric cancer is the fifth most common malignancy and the third leading cause of cancer-related deaths worldwide. Chemotherapies against gastric cancer often fail, with cancer recurrence due potentially to the persistence of cancer stem cells. This unique subpopulation of cells in tumors possess the ability to self-renew and de-differentiate. These cancer stem cells are critical for initiation, maintenance, metastasis, and relapse of cancers; however, the molecular mechanisms supporting cancer stemness remain largely unknown...
January 12, 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29329108/cracking-novel-shared-targets-between-epilepsy-and-alzheimer-s-disease-need-of-the-hour
#3
Nitika Garg, Rupa Joshi, Bikash Medhi
Epilepsy and Alzheimer's disease (AD) are interconnected. It is well known that seizures are linked with cognitive impairment, and there are various shared etiologies between epilepsy and AD. The connection between hyperexcitability of neurons and cognitive dysfunction in the progression of AD or epileptogenesis plays a vital role for improving selection of treatment for both diseases. Traditionally, seizures occur less frequently and in later stages of age in patients with AD which in turn implies that neurodegeneration causes seizures...
January 12, 2018: Reviews in the Neurosciences
https://www.readbyqxmd.com/read/29323740/long-non-coding-rna-asbel-promotes-osteosarcoma-cell-proliferation-migration-and-invasion-by-regulating-microrna-21
#4
Jianhui Zhao, Zhongli Gao, Chao Zhang, Han Wu, Rui Gu, Rui Jiang
Osteosarcoma is the most common malignant bone tumor in children and adolescents with high rate of incidence, high frequency of recurrence and high degree of metastasis. This study aimed to investigate the effects of long noncoding RNA antisense ncRNA in the Abundant in neuroepithelium area (ANA)/B-cell translocation gene 3 (BTG3) locus (lncRNA ASBEL) on the pathogenesis of osteosarcoma. The expression levels of ASBEL in human osteoblast cells and human osteosarcoma cells were evaluated using qRT-PCR. Effects of ASBEL knockdown on cell viability, migration and invasion were detected using trypan blue exclusion assay, cell migration and invasion assay, respectively...
January 11, 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29321323/hiv-1-vif-s-capacity-to-manipulate-the-cell-cycle-is-species-specific
#5
Edward L Evans, Jordan T Becker, Stephanie L Fricke, Kishan Patel, Nathan M Sherer
Cells derived from mice and other rodents exhibit profound blocks to HIV-1 virion production reflecting species-specific incompatibilities between viral Tat and Rev proteins and essential host factors Cyclin T1 (CCNT1) and Exportin-1 (XPO1, also known as CRM1), respectively. To determine if mouse cell blocks other than CCNT1 and XPO1 affect HIV's post-integration stages, we studied HIV-1NL4-3 gene expression in mouse NIH 3T3 cells modified to constitutively express HIV-1 compatible versions of CCNT1 and XPO1 (3T3...
January 10, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29317521/ca2-dependent-demethylation-of-phosphatase-pp2ac-promotes-glucose-deprivation-induced-cell-death-independently-of-inhibiting-glycolysis
#6
Ha Yin Lee, Yoko Itahana, Stefan Schuechner, Masahiro Fukuda, H Shawn Je, Egon Ogris, David M Virshup, Koji Itahana
Cancer cells increase glucose metabolism to support aerobic glycolysis. However, only some cancer cells are acutely sensitive to glucose withdrawal, and the underlying mechanism of this selective sensitivity is unclear. We showed that glucose deprivation initiates a cell death pathway in cancer cells that is dependent on the kinase RIPK1. Glucose withdrawal triggered rapid plasma membrane depolarization and an influx of extracellular calcium into the cell through the L-type calcium channel Cav1.3 (CACNA1D), followed by activation of the kinase CAMK1...
January 9, 2018: Science Signaling
https://www.readbyqxmd.com/read/29307602/essential-roles-of-akt-snail-pathway-in-microcystin-lr-induced-tight-junction-toxicity-in-sertoli-cell
#7
Yuan Zhou, Xiao Geng, Yu Chen, Hao Shi, Yan Yang, Chan Zhu, Guang Yu, Zongxiang Tang
Microcystin (MC)-LR is a cyclic heptapeptide that acts as a potent reproductive system toxin. However, the underlying pathways of MCLR-induced reproductive system toxicity have not been well elucidated. The blood-testis barrier is mainly constituted by tight junctions (TJs) between adjacent Sertoli cells in the seminiferous epithelium near the basement membrane. The present study was designed to investigate changes in TJs and the underlying pathway in MC-LR-induced TJs toxicity in Sertoli cell. In our study, the transepithelial electrical resistance (TER) value was decreased in a dose dependent manner due to the markers of TJs occludin, claudin and zonula occludens-1 (ZO-1) expression decline...
January 4, 2018: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/29303964/new-interactors-of-the-truncated-ebna-lp-protein-identified-by-mass-spectrometry-in-p3hr1-burkitt-s-lymphoma-cells
#8
Sonia Chelouah, Emilie Cochet, Sophie Couvé, Sandy Balkaran, Aude Robert, Evelyne May, Vasily Ogryzko, Joëlle Wiels
The Epstein-Barr virus nuclear antigen leader protein (EBNA-LP) acts as a co-activator of EBNA-2, a transcriptional activator essential for Epstein-Barr virus (EBV)-induced B-cell transformation. Burkitt's lymphoma (BL) cells harboring a mutant EBV strain that lacks both the EBNA-2 gene and 3' exons of EBNA-LP express Y1Y2-truncated isoforms of EBNA-LP (tEBNA-LP) and better resist apoptosis than if infected with the wild-type virus. In such BL cells, tEBNA-LP interacts with the protein phosphatase 2A (PP2A) catalytic subunit (PP2A C), and this interaction likely plays a role in resistance to apoptosis...
January 5, 2018: Cancers
https://www.readbyqxmd.com/read/29299971/the-role-of-the-fas-fasl-signaling-pathway-in-environmental-toxicant-induced-testicular-cell-apoptosis-an-update
#9
Mei Wang, Ping Su
The Fas/FasL signaling pathway is one of the major pathways that regulate apoptosis. Increasing studies have shown that the activation of the Fas/FasL signaling pathway is closely associated with testicular cell apoptosis. However, the mechanism involved is still unclear. We discuss recent findings regarding the molecular mechanisms by which environmental toxicants induce testicular pathology via Fas/FasL signaling. These findings suggest that Fas/FasL signaling is employed to impact the sensitivity (a response to external factors) of germ cells, disrupt steroidogenic hormone and cytokine metabolism mediated by Sertoli cells, and elicit the activation of NFAT (nuclear factor of activated T-cells) in Leydig cell apoptosis...
January 4, 2018: Systems Biology in Reproductive Medicine
https://www.readbyqxmd.com/read/29290611/the-ebola-virus-nucleoprotein-recruits-the-host-pp2a-b56-phosphatase-to-activate-transcriptional-support-activity-of-vp30
#10
Thomas Kruse, Nadine Biedenkopf, Emil Peter Thrane Hertz, Erik Dietzel, Gertrud Stalmann, Blanca López-Méndez, Norman E Davey, Jakob Nilsson, Stephan Becker
Transcription of the Ebola virus genome depends on the viral transcription factor VP30 in its unphosphorylated form, but the underlying molecular mechanism of VP30 dephosphorylation is unknown. Here we show that the Ebola virus nucleoprotein (NP) recruits the host PP2A-B56 protein phosphatase through a B56-binding LxxIxE motif and that this motif is essential for VP30 dephosphorylation and viral transcription. The LxxIxE motif and the binding site of VP30 in NP are in close proximity, and both binding sites are required for the dephosphorylation of VP30...
December 27, 2017: Molecular Cell
https://www.readbyqxmd.com/read/29290562/cell-size-and-growth-rate-are-modulated-by-torc2-dependent-signals
#11
Rafael Lucena, Maria Alcaide-Gavilán, Katherine Schubert, Maybo He, Matthew G Domnauer, Catherine Marquer, Christian Klose, Michal A Surma, Douglas R Kellogg
The size of all cells, from bacteria to vertebrates, is proportional to the growth rate set by nutrient availability, but the underlying mechanisms are unknown. Here, we show that nutrients modulate cell size and growth rate via the TORC2 signaling network in budding yeast. An important function of the TORC2 network is to modulate synthesis of ceramide lipids, which play roles in signaling. TORC2-dependent control of ceramide signaling strongly influences both cell size and growth rate. Thus, cells that cannot make ceramides fail to modulate their growth rate or size in response to changes in nutrients...
December 20, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/29288365/methylphenidate-disrupts-cytoskeletal-homeostasis-and-reduces-membrane-associated-lipid-content-in-juvenile-rat-hippocampus
#12
Felipe Schmitz, Paula Pierozan, Helena Biasibetti-Brendler, Fernanda Silva Ferreira, Fernanda Dos Santos Petry, Vera Maria Treis Trindade, Regina Pessoa-Pureur, Angela T S Wyse
Although methylphenidate (MPH) is ubiquitously prescribed to children and adolescents, the consequences of chronic utilization of this psychostimulant are poorly understood. In this study, we investigated the effects of MPH on cytoskeletal homeostasis and lipid content in rat hippocampus. Wistar rats received intraperitoneal injections of MPH (2.0 mg/kg) or saline solution (controls), once a day, from the 15th to the 44th day of age. Results showed that MPH provoked hypophosphorylation of glial fibrillary acidic protein (GFAP) and reduced its immunocontent...
December 29, 2017: Metabolic Brain Disease
https://www.readbyqxmd.com/read/29281045/protein-phosphatase-2a-and-its-methylation-modulating-enzymes-lcmt-1-and-pme-1-are-dysregulated-in-tauopathies-of-progressive-supranuclear-palsy-and-alzheimer-disease
#13
Hye-Jin Park, Kang-Woo Lee, Stephanie Oh, Run Yan, Jie Zhang, Thomas G Beach, Charles H Adler, Michael Voronkov, Steven P Braithwaite, Jeffry B Stock, M Maral Mouradian
Hyperphosphorylated tau aggregates are characteristic of tauopathies including progressive supranuclear palsy (PSP) and Alzheimer disease (AD), but factors contributing to pathologic tau phosphorylation are not well understood. Here, we studied the regulation of the major tau phosphatase, the heterotrimeric AB55αC protein phosphatase 2 A (PP2A), in PSP and AD. The assembly and activity of this PP2A isoform are regulated by reversible carboxyl methylation of its catalytic C subunit, while the B subunit confers substrate specificity...
December 21, 2017: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/29280352/mg-al-and-zn-al-layered-double-hydroxides-promote-dynamic-expression-of-marker-genes-in-osteogenic-differentiation-by-modulating-mitogen-activated-protein-kinases
#14
Ha Ram Kang, Célio Junior da Costa Fernandes, Rodrigo Augusto da Silva, Vera Regina Leopoldo Constantino, Ivan Hong Jun Koh, Willian F Zambuzzi
The effect of LDH samples comprised of chloride anions intercalated between positive layers of magnesium/aluminum (Mg-Al LDH) or zinc/aluminum (Zn-Al LDH) chemical composition on pre-osteoblast performance is investigated. Non-cytotoxic concentrations of both LDHs modulated pre-osteoblast adhesion by triggering cytoskeleton rearrangement dependent on recruiting of Cofilin, which is modulated by the inhibition of the Protein Phosphatase 2A (PP2A), culminating in osteoblast differentiation with a significant increase of osteogenic marker genes...
December 27, 2017: Advanced Healthcare Materials
https://www.readbyqxmd.com/read/29275362/regulation-of-%C3%AE-catenin-phosphorylation-by-pr55%C3%AE-in-adenoid-cystic-carcinoma
#15
Kana Ishibashi, Kotaro Ishii, Goro Sugiyama, Y U Kamata, Azusa Suzuki, Wataru Kumamaru, Yukiko Ohyama, Hiroyuki Nakano, Tamotsu Kiyoshima, Tomoki Sumida, Tomohiro Yamada, Yoshihide Mori
BACKGROUND/AIM: Adenoid cystic carcinoma (AdCC) is a rare cancer of the salivary gland with high risk of recurrence and metastasis. Wnt signalling is critical for determining tumor grade in AdCC, as it regulates invasion and migration. β-catenin dephosphorylation plays an important role in the Wnt pathway, but its underlying molecular mechanism remains unclear. MATERIALS AND METHODS: Because the regulatory subunits of protein phosphatase 2A (PP2A) drive Wnt signalling via target molecules, including β-catenin, we used qRT-PCR and immunoblot analysis to investigate the expression of these subunits in an AdCC cell line (ACCS) and a more aggressive subline (ACCS-M)...
January 2018: Cancer Genomics & Proteomics
https://www.readbyqxmd.com/read/29273778/methylation-regulated-decommissioning-of-multimeric-pp2a-complexes
#16
Cheng-Guo Wu, Aiping Zheng, Li Jiang, Michael Rowse, Vitali Stanevich, Hui Chen, Yitong Li, Kenneth A Satyshur, Benjamin Johnson, Ting-Jia Gu, Zuojia Liu, Yongna Xing
Dynamic assembly/disassembly of signaling complexes are crucial for cellular functions. Specialized latency and activation chaperones control the biogenesis of protein phosphatase 2A (PP2A) holoenzymes that contain a common scaffold and catalytic subunits and a variable regulatory subunit. Here we show that the butterfly-shaped TIPRL (TOR signaling pathway regulator) makes highly integrative multibranching contacts with the PP2A catalytic subunit, selective for the unmethylated tail and perturbing/inactivating the phosphatase active site...
December 22, 2017: Nature Communications
https://www.readbyqxmd.com/read/29262338/homeostatic-control-of-hpo-mst-kinase-activity-through-autophosphorylation-dependent-recruitment-of-the-stripak-pp2a-phosphatase-complex
#17
Yonggang Zheng, Bo Liu, Li Wang, Huiyan Lei, Katiuska Daniela Pulgar Prieto, Duojia Pan
The Hippo pathway controls organ size and tissue homeostasis through a kinase cascade leading from the Ste20-like kinase Hpo (MST1/2 in mammals) to the transcriptional coactivator Yki (YAP/TAZ in mammals). Whereas previous studies have uncovered positive and negative regulators of Hpo/MST, how they are integrated to maintain signaling homeostasis remains poorly understood. Here, we identify a self-restricting mechanism whereby autophosphorylation of an unstructured linker in Hpo/MST creates docking sites for the STRIPAK PP2A phosphatase complex to inactivate Hpo/MST...
December 19, 2017: Cell Reports
https://www.readbyqxmd.com/read/29261144/pp2a-as-the-main-node-of-therapeutic-strategies-and-resistance-reversal-in-triple-negative-breast-cancer
#18
REVIEW
Henan Zhao, Duojiao Li, Baojing Zhang, Yan Qi, Yunpeng Diao, Yuhong Zhen, Xiaohong Shu
Triple negative breast cancer (TNBC), is defined as a type of tumor lacking the expression of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2). The ER, PR and HER2 are usually the molecular therapeutic targets for breast cancers, but they are ineffective for TNBC because of their negative expressions, so chemotherapy is currently the main treatment strategy in TNBC. However, drug resistance remains a major impediment to TNBC chemotherapeutic treatment. Recently, the protein phosphatase 2A (PP2A) has been found to regulate the phosphorylation of some substrates involved in the relevant target of TNBC, such as cell cycle control, DNA damage responses, epidermal growth factor receptor, immune modulation and cell death resistance, which may be the effective therapeutic strategies or influence drug sensitivity to TNBCs...
December 20, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29247302/purification-of-target-proteins-from-native-tissues-cct-complex-from-bovine-testes-and-pp2ac-from-porcine-brains
#19
Feng Guo, Nathan Wlodarchak, Patrick Menden, Yongna Xing
Proteomics is a powerful approach for systematic identification and quantification of the entire proteome of a biological system (cell, tissue, organ, biological fluid, or organism) at specific time points ( http://www.nature.com ). Extracting and purifying target proteins from native tissues are essential steps for many aspects of proteomic studies. In this chapter, we will introduce the experimental procedures to obtain soluble proteins from two different tissues: (1) the CCT (cpn-containing TCP-1) complex from bovine testes and (2) the protein phosphatase 2A (PP2A) catalytic subunit (PP2Ac or C) from porcine brains...
December 17, 2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29241734/maduramicin-activated-protein-phosphatase-2a-results-in-extracellular-signal-regulated-kinase-1-2-inhibition-leading-to-cytotoxicity-in-myocardial-h9c2-cells
#20
Xin Chen, Shanxiang Jiang
Maduramicin, a polyether ionophore antibiotic used as an anticoccidial agent in poultry industry, has been reported to be toxic to animals and humans if improperly used or by accident, resulting in heart failure, skeletal muscle degeneration and even death. However, the molecular mechanism underlying its cardiotoxicity remains elusive. Mitogen activated protein kinases (MAPKs) and protein phosphatases signaling pathways have been documented to be involved in the cell survival regulation. The present study was set to investigate the role of above pathways in maduramicin-induced myocardial cytotoxicity...
December 11, 2017: Toxicology Letters
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