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https://www.readbyqxmd.com/read/29398519/compound-c-enhances-tau-phosphorylation-at-serine396-via-pi3k-activation-in-an-ampk-and-rapamycin-independent-way-in-differentiated-sh-sy5y-cells
#1
Shohreh Majd, Simon Koblar, John Power
Aggregation of hyperphosphorylated tau (p-tau) in the form of neurofibrillary tangles (NFT) is a main hallmark for Alzheimer's disease (AD). Activation of cellular metabolic axis, made of adenosine monophosphate kinase protein kinase (AMPK) and mammalian target of rapamycin (mTOR) have been implicated in generating tau pathology of AD. Thus, blocking either of these two proteins or both, are suggested as the future therapeutic approaches for AD. How and to what level these approaches could be applied, however are not entirely clear...
January 31, 2018: Neuroscience Letters
https://www.readbyqxmd.com/read/29393542/cucurbitacin-b-induces-inhibitory-effects-via-cip2a-pp2a-akt-pathway-in-glioblastoma-multiforme
#2
Shanshan Qin, Jing Li, Yuan Si, Zhongwei He, Te Zhang, Dawei Wang, Xuewen Liu, Yang Guo, Liang Zhang, Shan Li, Qiang Li, Ying Liu
Cancerous inhibitor of protein phosphatase 2A (CIP2A) is a human oncoprotein that is overexpressed in multiple types of tumors and promotes the proliferation and transformation of cancer cells. However, whether CIP2A can be a new drug target for human glioblastoma multiforme (GBM) is largely unclear. In the present study, we demonstrated that the overexpression of CIP2A promotes invasive behavior in GBM, and a natural compound, cucurbitacin B (CuB), shows an anti-proliferative and anti-invasion effect in GBM cell lines...
February 2, 2018: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/29385539/foxg1-overexpression-in-neocortical-pyramids-stimulates-dendrite-elongation-via-hes1-and-pcreb1-upregulation
#3
Simone Chiola, Mihn Duc Do, Lucy Centrone, Antonello Mallamaci
The architecture of neocortical projection neurons is subject of a complex gene control. Here we demonstrated that Foxg1, a transcription factor gene which patterns the early rostral brain and sets the pace of telencephalic neuronogenesis, specifically stimulates dendrite elongation. This phenomenon occurs in vivo like in vitro, and it is detectable even upon moderate changes of Foxg1 expression levels. We found that Foxg1 acts by stimulating Hes1, which in turn upregulates pCreb1, a well-known pro-dendritogenic effector, and downregulates Syt and Ndr1, namely two established antagonizers of dendrite elongation...
January 28, 2018: Cerebral Cortex
https://www.readbyqxmd.com/read/29334873/nobiletin-prevents-cadmium-induced-neuronal-apoptosis-by-inhibiting-reactive-oxygen-species-and-modulating-jnk-erk1-2-and-akt-mtor-networks-in-rats
#4
Youyang Qu, Yu Liu, Li Chen, Yanmei Zhu, Xingjun Xiao, Di Wang, Yulan Zhu
Objectives Cadmium (Cd), an extremely noxious environmental pollutant is known to induce oxidative stress leading to neurodegenerative diseases. Nobiletin, a citrus flavonoid is reported to possess various pharmacological properties. This study investigates the effects of nobiletin over Cd-induced neuronal apoptosis in rodent experimental model. Methods To separate group of male Sprague Dawley rats, Cd (2 mL/kg/day) was subcutaneously injected for one month which results in a dose level of 1 mg/kg Cd. Couple of days prior to Cd injection, the treatment group rats regularly received nobiletin (50, 100, or 200 mg/kg b...
January 16, 2018: Neurological Research
https://www.readbyqxmd.com/read/29331388/e4bp4-inhibits-angii-induced-apoptosis-in-h9c2-cardiomyoblasts-by-activating-the-pi3k-akt-pathway-and-promoting-calcium-uptake
#5
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/29323740/long-non-coding-rna-asbel-promotes-osteosarcoma-cell-proliferation-migration-and-invasion-by-regulating-microrna-21
#6
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/29214724/cme-1-a-novel-polysaccharide-suppresses-inos-expression-in-lipopolysaccharide-stimulated-macrophages-through-ceramide-initiated-protein-phosphatase-2a-activation
#7
Joen-Rong Sheu, Zhih-Cherng Chen, Ming-Jen Hsu, Shwu-Huey Wang, Kuo-Wei Jung, Wei-Fan Wu, Szu-Han Pan, Ruei-Dun Teng, Chih-Hao Yang, Cheng-Ying Hsieh
CME-1, a novel water-soluble polysaccharide purified from Ophiocordyceps sinensis mycelia, has anti-oxidative, antithrombotic and antitumour properties. In this study, other major attributes of CME-1, namely anti-inflammatory and immunomodulatory properties, were investigated. Treating lipopolysaccharide (LPS)-stimulated RAW 264.7 cells with CME-1 concentration-dependently suppressed nitric oxide formation and inducible nitric oxide synthase (iNOS) expression. In the CME-1-treated RAW 264.7 cells, LPS-induced IκBα degradation and the phosphorylation of p65, Akt and mitogen-activated protein kinases (MAPKs), including extracellular signal-regulated kinase, c-Jun N-terminal kinase and p38, were reduced...
December 7, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29186909/ketamine-a-clinically-used-anesthetic-inhibits-vascular-smooth-muscle-cell-proliferation-via-pp2a-activated-pi3k-akt-erk-inhibition
#8
Yi Chang, Jiun-Yi Li, Thanasekaran Jayakumar, Shou-Huang Hung, Wei-Cheng Lee, Manjunath Manubolu, Joen-Rong Sheu, Ming-Jen Hsu
Abnormal proliferation of vascular smooth muscle cells (VSMCs) gives rise to major pathological processes involved in the development of cardiovascular diseases. The use of anti-proliferative agents for VSMCs offers potential for the treatment of vascular disorders. Intravenous anesthetics are firmly established to have direct effects on VSMCs, resulting in modulation of blood pressure. Ketamine has been used for many years in the intensive care unit (ICU) for sedation, and has recently been considered for adjunctive therapy...
November 27, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29113343/pp2a-mediates-apoptosis-or-autophagic-cell-death-in-multiple-myeloma-cell-lines
#9
Hang Zhou, Wei Luo, Chao Zeng, Yu Zhang, Liyang Wang, Wenxiu Yao, Chunlai Nie
The crosstalk between apoptosis and autophagy contributes to tumorigenesis and cancer therapy. The process by which BetA (betulinic acid), a naturally occurring triterpenoid, regulates apoptosis and autophagy as a cancer therapy is unclear. In this study, we show for the first time that protein phosphatase 2A (PP2A) acts as a switch to regulate apoptosis and autophagic cell death mediated by BetA. Under normal conditions, caspase-3 is activated by the mitochondrial pathway upon BetA treatment. Activated caspase-3 cleaves the A subunit of PP2A (PP2A/A), resulting in the association of PP2A and Akt...
October 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/29079657/torc1-and-torc2-converge-to-regulate-the-saga-co-activator-in-response-to-nutrient-availability
#10
Thomas Laboucarié, Dylane Detilleux, Ricard A Rodriguez-Mias, Céline Faux, Yves Romeo, Mirita Franz-Wachtel, Karsten Krug, Boris Maček, Judit Villén, Janni Petersen, Dominique Helmlinger
Gene expression regulation is essential for cells to adapt to changes in their environment. Co-activator complexes have well-established roles in transcriptional regulation, but less is known about how they sense and respond to signaling cues. We have previously shown that, in fission yeast, one such co-activator, the SAGA complex, controls gene expression and the switch from proliferation to differentiation in response to nutrient availability. Here, using a combination of genetic, biochemical, and proteomic approaches, we show that SAGA responds to nutrients through the differential phosphorylation of its Taf12 component, downstream of both the TORC1 and TORC2 pathways...
October 27, 2017: EMBO Reports
https://www.readbyqxmd.com/read/29056830/aloperine-protects-mice-against-dss-induced-colitis-by-pp2a-mediated-pi3k-akt-mtor-signaling-suppression
#11
Xiaoxia Fu, Fei Sun, Faxi Wang, Junai Zhang, Biying Zheng, Jixin Zhong, Tiantian Yue, Xuebao Zheng, Jun-Fa Xu, Cong-Yi Wang
Colitis is a major form of inflammatory bowel disease which involved mucosal immune dysfunction. Aloperine is an alkaloid isolated from the shrub Sophora alopecuroides L. and has been recognized as an effective treatment for inflammatory and allergic diseases. The present study aimed to examine the molecular mechanisms underlying aloperine-mediated colitis protection. We found that aloperine treatment improved colitis induced by dextran sodium sulfate (DSS) based on body weight, disease activity index, colonic length, and spleen index...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/29054680/phosphorylation-of-protein-phosphatase-2a-facilitated-an-early-stage-of-chemical-carcinogenesis
#12
Yuji Ishii, Ken Kuroda, Kohei Matsushita, Yuh Yokoo, Shinji Takasu, Aki Kijima, Takehiko Nohmi, Kumiko Ogawa, Takashi Umemura
Protein phosphatase 2A (PP2A) is a serine-threonine phosphatase that regulates cell signaling pathways. Its inactivation is correlated with tumor malignancy, possibly due to the effects on cell differentiation and malignant cell transformation. Therefore, it has been noted that PP2A could be a promising target for cancer therapy. In our previous study of the hepatocarcinogen estragole (ES), cell proliferation may be required to convert ES-specific DNA adducts to mutations. To explore the trigger for cell proliferation, gpt delta rats were administered ES by gavage at doses of 3, 30 and 300mg/kg/day for 4weeks...
October 17, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28963856/dopamine-d2-receptor-signaling-controls-inflammation-in-acute-pancreatitis-via-pp2a-dependent-akt-nf%C3%AE%C2%BAb-signaling-pathway
#13
Xiao Han, Bin Li, Xin Ye, Tunike Mulatibieke, Jianghong Wu, Juanjuan Dai, Deqing Wu, Jianbo Ni, Ruling Zhang, Jing Xue, Rong Wan, Xingpeng Wang, Guoyong Hu
BACKGROUND AND PURPOSE: Dopamine (DA) has multiple anti-inflammatory effects, but its role and molecular mechanism in acute pancreatitis (AP) is unclear. We investigated the role of DA signaling on inflammatory response in AP. EXPERIMENTAL APPROACH: We analyzed the changes of pancreatic dopaminergic system and effects of DA, antagonists and agonists of DA receptor (DRD)1 and 2 in wild-type and pancreas-specific Drd2(-/-) mice with AP (induced by caerulein and lipopolysaccharide or L-Arginine) or in pancreatic acinar cells with or without CCK stimulation...
September 30, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28941043/cocr-enriched-medium-modulates-integrin-based-downstream-signaling-and-requires-a-set-of-inflammatory-genes-reprograming-in-vitro
#14
Célio J C Fernandes, Fabio Bezerra, Maiara das D do Carmo, Georgia Feltran, Mariana C Rossi, Rodrigo A da Silva, Pedro de M Padilha, Willian F Zambuzzi
Significant health concerns have been raised by the high levels of Cr and Co ions into whole blood as resulted of corrosion process released from biomedical implants, but very little is known about their biological behavior in governing cell metabolism. Thus, we prompted to address this issue by exploring the effects of CoCr enriched medium on both fibroblast and pre-osteoblast (pre-Ob) cells. Firstly, we showed there is a significant difference in Co and Cr releasing dependent on engineered surface, it being even more released in dual acid-etching treating surface (named w/DAE) than the machined surfaces (named wo/DAE)...
September 22, 2017: Journal of Biomedical Materials Research. Part A
https://www.readbyqxmd.com/read/28938602/activation-of-cancerous-inhibitor-of-pp2a-cip2a-contributes-to-lapatinib-resistance-through-induction-of-cip2a-akt-feedback-loop-in-erbb2-positive-breast-cancer-cells
#15
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...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28919038/covalent-ligand-discovery-against-druggable-hotspots-targeted-by-anti-cancer-natural-products
#16
Elizabeth A Grossman, Carl C Ward, Jessica N Spradlin, Leslie A Bateman, Tucker R Huffman, David K Miyamoto, Jordan I Kleinman, Daniel K Nomura
Many natural products that show therapeutic activities are often difficult to synthesize or isolate and have unknown targets, hindering their development as drugs. Identifying druggable hotspots targeted by covalently acting anti-cancer natural products can enable pharmacological interrogation of these sites with more synthetically tractable compounds. Here, we used chemoproteomic platforms to discover that the anti-cancer natural product withaferin A targets C377 on the regulatory subunit PPP2R1A of the tumor-suppressor protein phosphatase 2A (PP2A) complex leading to activation of PP2A activity, inactivation of AKT, and impaired breast cancer cell proliferation...
November 16, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/28875582/identification-of-signaling-pathways-targeted-by-the-food-contaminant-fb1-transcriptome-and-kinome-analysis-of-samples-from-pig-liver-and-intestine
#17
Marion Régnier, Pascal Gourbeyre, Philippe Pinton, Scott Napper, Joëlle Laffite, Anne-Marie Cossalter, Jean-Denis Bailly, Yannick Lippi, Justine Bertrand-Michel, Ana Paula F R L Bracarense, Hervé Guillou, Nicolas Loiseau, Isabelle P Oswald
SCOPE: Fumonisin B1 (FB1) is a mycotoxin produced by Fusarium species. In mammals, this toxin causes widespread organ-specific damage; it promotes hepatotoxicity, is immunotoxic, alters intestinal functions… Despite its inhibitory effect on de novo ceramide synthesis, its molecular mechanism of action and toxicity are not totally elucidated. METHOD & RESULTS: To explore the mechanism of FB1 toxicity, we analyzed the transcriptome and kinome of two organs targeted by FB1: the liver and the jejunum...
September 5, 2017: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/28830934/op449-inhibits-breast-cancer-growth-without-adverse-metabolic-effects
#18
Gadi Shlomai, Zara Zelenko, Irini Markella Antoniou, Marilyn Stasinopoulos, Aviva Tobin-Hess, Michael P Vitek, Derek LeRoith, Emily Jane Gallagher
Hyperinsulinemia is associated with a decrease in breast cancer recurrence-free survival and overall survival. Inhibition of insulin receptor signaling is associated with glycemic dysregulation. SET is a direct modulator of PP2A, which negatively regulates the PI3K/AKT/mTOR pathway. OP449, a SET inhibitor, decreases AKT/mTOR activation. The effects of OP449 treatment on breast cancer growth in the setting of pre-diabetes, and its metabolic implications are currently unknown. We found that the volumes and weights of human MDA-MB-231 breast cancer xenografts were greater in hyperinsulinemic mice compared with controls (P < 0...
October 2017: Endocrine-related Cancer
https://www.readbyqxmd.com/read/28822962/glucose-transporter-4-glut4-deficient-hearts-develop-maladaptive-hypertrophy-in-response-to-physiologic-or-pathologic-stresses
#19
Adam Raymond Wende, Jaetaek Kim, William Holland, Benjamin E Wayment, Brian T O'Neill, Joseph Tuinei, Manoja K Brahma, Mark E Pepin, Mark A McCrory, Ivan Luptak, Ganesh V Halade, Sheldon E Litwin, E Dale Abel
Pathological cardiac hypertrophy may be associated with reduced expression of the GLUT4 glucose transporter in contrast to exercise-induced cardiac hypertrophy, where GLUT4 levels are increased. However, mice with cardiac specific deletion of GLUT4 (G4H-/-) have normal cardiac function in the unstressed state. This study tested the hypothesis that cardiac GLUT4 is required for myocardial adaptations to hemodynamic demands. G4H-/- and control littermates (Con) were subjected to either a pathological model of left ventricular pressure overload (transverse aortic constriction; TAC) or a physiological model of endurance exercise (swim training)...
August 19, 2017: American Journal of Physiology. Heart and Circulatory Physiology
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
#20
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
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