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https://www.readbyqxmd.com/read/29623928/effect-of-tibolone-pretreatment-on-kinases-and-phosphatases-that-regulate-the-expression-and-phosphorylation-of-tau-in-the-hippocampus-of-rats-exposed-to-ozone
#1
Rodolfo Pinto-Almazan, Julia J Segura-Uribe, Marvin A Soriano-Ursúa, Eunice D Farfán-García, Juan M Gallardo, Christian Guerra-Araiza
Oxidative stress (OS) is a key process in the development of many neurodegenerative diseases, memory disorders, and other pathological processes related to aging. Tibolone (TIB), a synthetic hormone used as a treatment for menopausal symptoms, decreases lipoperoxidation levels, prevents memory impairment and learning disability caused by ozone (O3 ) exposure. However, it is not clear if TIB could prevent the increase in phosphorylation induced by oxidative stress of the microtubule-associated protein Tau. In this study, the effects of TIB at different times of administration on the phosphorylation of Tau, the activation of glycogen synthase kinase-3β (GSK3β), and the inactivation of Akt and phosphatases PP2A and PTEN induced by O3 exposure were assessed in adult male Wistar rats...
March 2018: Neural Regeneration Research
https://www.readbyqxmd.com/read/29530069/inhibition-of-creb-binding-protein-beta-catenin-signaling-down-regulates-cd133-expression-and-activates-pp2a-pten-signaling-in-tumor-initiating-liver-cancer-cells
#2
Yuanyuan Tang, Joshua Berlind, Nirmala Mavila
BACKGROUND: The WNT-beta-catenin pathway is known to regulate cellular homeostasis during development and tissue regeneration. Activation of WNT signaling increases the stability of cytoplasmic beta-catenin and enhances its nuclear translocation. Nuclear beta-catenin function is regulated by transcriptional co-factors such as CREB binding protein (CBP) and p300. Hyper-activated WNT-beta-catenin signaling is associated with many cancers. However, its role in inducing stemness to liver cancer cells, its autoregulation and how it regulates tumor suppressor pathways are not well understood...
March 12, 2018: Cell Communication and Signaling: CCS
https://www.readbyqxmd.com/read/29511968/amphetamine-neurotoxicity-in-pc12-cells-through-the-pp2a-akt-gsk3%C3%AE-pathway
#3
Wenji He, Xinyu Yan, Sanqiang Pan
Amphetamine (AMPH) abuse can influence neuropsychiatric disorders and cell apoptosis by interfering with the protein kinase B/ glycogen synthase kinase 3 beta (AKT/GSK3β) pathway. However, the mechanisms underlying this regulation are poorly understood. Using PC12 cells, we found that AMPH inhibited AKT and GSK-3β phosphorylation levels and increased total GSK-3β levels. Furthermore, AMPH caused an increase in the activity of protein phosphatase 2 (PP2A), a signaling protein upstream of AKT, which in turn inhibited phosphorylated AKT levels...
March 6, 2018: Neurotoxicity Research
https://www.readbyqxmd.com/read/29500169/antiphospholipid-antibodies-induce-thrombosis-by-pp2a-activation-via-apoer2-dab2-shc1-complex-formation-in-endothelium
#4
Anastasia Sacharidou, Ken L Chambliss, Victoria Ulrich, Jane E Salmon, Yu-Min Shen, Joachim Herz, David Y Hui, Lance S Terada, Philip W Shaul, Chieko Mineo
In the antiphospholipid syndrome (APS), antiphospholipid antibody (aPL) recognition of β2 glycoprotein (β2GPI) promotes thrombosis, and preclinical studies indicate that this is due to endothelial NO synthase (eNOS) antagonism via apoER2-dependent processes. How apoER2 molecularly links these events is unknown. Here we show that in endothelial cells the apoER2 cytoplasmic tail serves as a scaffold for aPL-induced assembly and activation of the heterotrimeric protein phosphatase PP2A. Dab2 recruitment to the apoER2 NPXY motif promotes the activating L309 methylation of the PP2A catalytic subunit by leucine methyl transferase-1...
March 2, 2018: Blood
https://www.readbyqxmd.com/read/29470962/indomethacin-induced-glioma-apoptosis-involving-ceramide-signals
#5
Cheng-Yi Chang, Jian-Ri Li, Chih-Cheng Wu, Jiaan-Der Wang, Ching-Ping Yang, Wen-Ying Chen, Wen-Yi Wang, Chun-Jung Chen
Nonsteroidal anti-inflammatory drugs (NSAIDs) are increasingly implicated in the prevention and treatment of cancers apart from their known inhibitory effects on eicosanoid production. One of the NSAIDs, indomethacin, in particular shows promising antineoplastic outcome against glioma. To extend such finding, we here studied in human H4 and U87 glioma cells the possible involvement of the ceramide/protein phosphatase 2A (PP2A)/Akt axis in the indomethacin-induced apoptosis. We found that the induced apoptosis was accompanied by a series of biochemical events, including intracellular ceramide generation, PP2A activation, Akt dephosphorylation, Mcl-1 and FLICE inhibiting protein (FLIP) transcriptional downregulation, Bax mitochondrial distribution, and caspase 3 activation...
February 19, 2018: Experimental Cell Research
https://www.readbyqxmd.com/read/29464081/dapk-and-cip2a-are-involved-in-gas6-axl-mediated-schwann-cell-proliferation-in-a-rat-model-of-bilateral-cavernous-nerve-injury
#6
Yen-Lin Chen, Yi-Ting Tsai, Ting-Ting Chao, Yi-No Wu, Meng-Chuan Chen, Ying-Hung Lin, Chun-Hou Liao, Shang-Shing P Chou, Han-Sun Chiang
Purpose: Impotence is one of the major complications occurring in prostate cancer patients after radical prostectomy (RP). Self-repair of the injured nerve has been observed in animal models and in patients after RP. However, the downstream signalling is not well documented. Here, we found that the DAPK/CIP2A complex is involved in GAS6/AXL-related Schwann cell proliferation. Materials and Methods: The 3 groups were a sham group, a 14-day post-bilateral cavernous nerve injury (BCNI) group and a 28-day post-BCNI group...
January 19, 2018: Oncotarget
https://www.readbyqxmd.com/read/29462574/adiponectin-receptor-agonist-adiporon-decreased-ceramide-and-lipotoxicity-and-ameliorated-diabetic-nephropathy
#7
Sun Ryoung Choi, Ji Hee Lim, Min Young Kim, Eun Nim Kim, Yaeni Kim, Beom Soon Choi, Yong-Soo Kim, Hye Won Kim, Kyung-Min Lim, Min Jeong Kim, Cheol Whee Park
BACKGROUND: Adiponectin is known to take part in the regulation of energy metabolism. AdipoRon, an orally-active synthetic adiponectin agonist, binds to both adiponectin receptors (AdipoR)1/R2 and ameliorates diabetic complications. Among the lipid metabolites, the ceramide subspecies of sphingolipids have been linked to features of lipotoxicity, including inflammation, cell death, and insulin resistance. We investigated the role of AdipoRon in the prevention and development of type 2 diabetic nephropathy...
February 17, 2018: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/29455644/mir-19b-enhances-proliferation-and-apoptosis-resistance-via-the-egfr-signaling-pathway-by-targeting-pp2a-and-bim-in-non-small-cell-lung-cancer
#8
Ulrich Baumgartner, Fabienne Berger, Ali Hashemi Gheinani, Sabrina Sofia Burgener, Katia Monastyrskaya, Erik Vassella
BACKGROUND: Epidermal growth factor receptor (EGFR) mutations enable constitutive active downstream signaling of PI3K/AKT, KRAS/ERK and JAK/STAT pathways, and promote tumor progression by inducing uncontrolled proliferation, evasion of apoptosis and migration of non-small cell lung cancer (NSCLC). In addition, such EGFR mutations increase the susceptibility of patients with NSCLC to tyrosine kinase inhibitor (TKI) therapy, but treated patients will invariably relapse with resistant disease...
February 19, 2018: Molecular Cancer
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
#9
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
#10
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
#11
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
#12
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...
March 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
#13
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...
February 15, 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
#14
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
#15
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...
February 2018: 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
#16
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
#17
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
#18
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...
December 2017: EMBO Reports
https://www.readbyqxmd.com/read/29056830/aloperine-protects-mice-against-dss-induced-colitis-by-pp2a-mediated-pi3k-akt-mtor-signaling-suppression
#19
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
#20
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...
December 1, 2017: Toxicology and Applied Pharmacology
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