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https://www.readbyqxmd.com/read/28822962/glucose-transporter-4-glut4-deficient-hearts-develop-maladaptive-hypertrophy-in-response-to-physiologic-or-pathologic-stresses
#1
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
#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/28765008/microcystin-leucine-arginine-exhibits-immunomodulatory-roles-in-testicular-cells-resulting-in-orchitis
#3
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
#4
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/28720534/tgf-%C3%AE-signaling-regulates-p-akt-levels-via-pp2a-during-diapause-entry-in-the-cotton-bollworm-helicoverpa-armigera
#5
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/28700668/conditional-cell-reprogramming-involves-non-canonical-%C3%AE-catenin-activation-and-mtor-mediated-inactivation-of-akt
#6
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
https://www.readbyqxmd.com/read/28603063/overexpression-of-phosphoprotein-phosphatase-2a-predicts-worse-prognosis-in-patients-with-breast-cancer-a-15-year-follow-up
#7
Po-Ming Chen, Pei-Yi Chu, Shiao-Lin Tung, Chun-Yu Liu, Yi-Fang Tsai, Yen-Shu Lin, Wan-Lun Wang, Yu-Ling Wang, Pei-Ju Lien, Ta-Chung Chao, Ling-Ming Tseng
Breast cancer subtypes can be stratified by immunohistochemical (IHC) expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor 2 (HER2). The signaling pathways mediated by these receptors are the dominant drivers of cell proliferation and survival in the majority of human breast cancers. One of the most frequently overactivated pathways in breast cancer is the AKT signaling cascade. Protein phosphatase 2A (PP2A) acts as a switch to turn off signal transduction in the AKT pathway; however, it is frequently inactivated in many cancers by phosphorylation of Tyr-307 to form phosphoprotein phosphatase 2A (p-PP2A)...
June 8, 2017: Human Pathology
https://www.readbyqxmd.com/read/28560452/arctigenin-inhibits-triple-negative-breast-cancers-by-targeting-cip2a-to-reactivate-protein-phosphatase-2a
#8
Qiuyue Huang, Shanshan Qin, Xiaoning Yuan, Liang Zhang, Juanli Ji, Xuewen Liu, Wenjing Ma, Yunfei Zhang, Pengfei Liu, Zhiting Sun, Jingxuan Zhang, Ying Liu
We have shown that a novel STAT3 inhibitor arctigenin (Atn) induces significant cytotoxicity in triple-negative breast cancer (TNBC) cells. This study further delineated molecular mechanisms where by Atn triggered cytotoxicity in TNBC cells. We found Atn can also inhibit metastasis in TNBC cells through cancerous inhibitor of protein phosphatase 2A (CIP2A) pathway. CIP2A is an endogenous inhibitor of protein phosphatase 2A (PP2A), which can increase the migration and invasion of various cancer cells. PP2A is a tumor suppressor, which is functionally defective in various cancers...
May 24, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28526544/interleukin-18-gene-deletion-protects-against-sepsis-induced-cardiac-dysfunction-by-inhibiting-pp2a-activity
#9
Yoshitaka Okuhara, Shunichi Yokoe, Toshihiro Iwasaku, Akiyo Eguchi, Koichi Nishimura, Wen Li, Makiko Oboshi, Yoshiro Naito, Toshiaki Mano, Michio Asahi, Haruki Okamura, Tohru Masuyama, Shinichi Hirotani
BACKGROUND: Interleukin-18 (IL-18) neutralization protects against lipopolysaccharide (LPS)-induced injuries, including myocardial dysfunction. However, the mechanism is yet to be fully elucidated. The aim of the present study was to determine whether IL-18 gene deletion prevents sepsis-induced cardiac dysfunction and to elucidate the potential mechanisms underlying IL-18-mediated cardiotoxicity by LPS. METHODS AND RESULTS: Ten-week-old male wild-type (WT) and IL-18 knockout (IL-18 KO) mice were intraperitoneally administered LPS...
September 15, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/28505155/oxidative-stress-and-expression-of-insulin-signaling-proteins-in-the-brain-of-diabetic-rats-role-of-nigella-sativa-oil-and-antidiabetic-drugs
#10
Mahmoud Balbaa, Shaymaa A Abdulmalek, Sofia Khalil
BACKGROUND AND OBJECTIVES: Insulin resistance of the brain is a specific form of type2-diabetes mellitus (T2DM) and the active insulin-signaling pathway plays a neuroprotective role against damaging conditions and Alzheimer's progression. The present study identifies the mediated emerging effects of the Nigella sativa oil (NSO) on the memory enhancing process, its anti-oxidative, acetylcholinestrase (AChE) inhibition, anti-brain insulin resistance and anti-amyloidogenic activities. In addition, the possible role of some anti-diabetic drugs in the neuro-protection processes and their effect in combination with NSO and/or the insulin receptor inhibitor IOMe-AG538 were investigated...
2017: PloS One
https://www.readbyqxmd.com/read/28421341/insufficient-activation-of-akt-upon-reperfusion-because-of-its-novel-modification-by-reduced-pp2a-b55%C3%AE-contributes-to-enlargement-of-infarct-size-by-chronic-kidney-disease
#11
Toshiyuki Tobisawa, Toshiyuki Yano, Masaya Tanno, Takayuki Miki, Atsushi Kuno, Yukishige Kimura, Satoko Ishikawa, Hidemichi Kouzu, Keitaro Nishizawa, Hideaki Yoshida, Tetsuji Miura
Chronic kidney disease (CKD) increases myocardial infarct size by an unknown mechanism. Here we examined the hypothesis that impairment of protective PI3K-PDK1-Akt and/or mTORC-Akt signaling upon reperfusion contributes to CKD-induced enlargement of infarct size. CKD was induced in rats by 5/6 nephrectomy (SNx group) 4 weeks before myocardial infarction experiments, and sham-operated rats served as controls (Sham group). Infarct size as a percentage of area at risk after ischemia/reperfusion was significantly larger in the SNx group than in the Sham group (56...
May 2017: Basic Research in Cardiology
https://www.readbyqxmd.com/read/28382174/cysteine-transporter-slc3a1-promotes-breast-cancer-tumorigenesis
#12
Yang Jiang, Yuan Cao, Yongbin Wang, Wei Li, Xinyi Liu, Yixuan Lv, Xiaoling Li, Jun Mi
Cysteine is an essential amino acid for infants, aged people as well as patients with metabolic disorders. Although the thiol group of cysteine side chain is active in oxidative reactions, the role of cysteine in cancer remains largely unknown. Here, we report that the expression level of the solute carrier family 3, member 1 (SLC3A1), the cysteine carrier, tightly correlated with clinical stages and patients' survival. Elevated SLC3A1 expression accelerated the cysteine uptake and the accumulation of reductive glutathione (GSH), leading to reduced reactive oxygen species (ROS)...
2017: Theranostics
https://www.readbyqxmd.com/read/28340282/carfilzomib-induces-leukaemia-cell-apoptosis-via-inhibiting-elk1-kiaa1524-elk-1-cip2a-and-activating-pp2a-not-related-to-proteasome-inhibition
#13
Chun-Yu Liu, Feng-Shu Hsieh, Pei-Yi Chu, Wen-Chun Tsai, Chun-Teng Huang, Yuan-Bin Yu, Tzu-Ting Huang, Po-Shen Ko, Man-Hsin Hung, Wan-Lun Wang, Chung-Wai Shiau, Kuen-Feng Chen
Enhancing the tumour suppressive activity of protein phosphatase 2A (PP2A) has been suggested to be an anti-leukaemic strategy. KIAA1524 (also termed CIP2A), an oncoprotein inhibiting PP2A, is associated with disease progression in chronic myeloid leukaemia and may be prognostic in cytogenetically normal acute myeloid leukaemia. Here we demonstrated that the selective proteasome inhibitor, carfilzomib, induced apoptosis in sensitive primary leukaemia cells and in sensitive leukaemia cell lines, associated with KIAA1524 protein downregulation, increased PP2A activity and decreased p-Akt, but not with the proteasome inhibition effect of carfilzomib...
June 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28300280/rapamycin-attenuates-baff-extended-proliferation-and-survival-via-disruption-of-mtorc1-2-signaling-in-normal-and-neoplastic-b-lymphoid-cells
#14
Qingyu Zeng, Shanshan Qin, Hai Zhang, Beibei Liu, Jiamin Qin, Xiaoxue Wang, Ruijie Zhang, Chunxiao Liu, Xiaoqing Dong, Shuangquan Zhang, Shile Huang, Long Chen
B cell activating factor from the TNF family (BAFF) stimulates B-cell proliferation and survival, but excessive BAFF promotes the development of aggressive B cells leading to malignant and autoimmune diseases. Recently, we have reported that rapamycin, a macrocyclic lactone, attenuates human soluble BAFF (hsBAFF)-stimulated B-cell proliferation/survival by suppressing mTOR-mediated PP2A-Erk1/2 signaling pathway. Here, we show that the inhibitory effect of rapamycin on hsBAFF-promoted B cell proliferation/survival is also related to blocking hsBAFF-stimulated phosphorylation of Akt, S6K1, and 4E-BP1, as well as expression of survivin in normal and B-lymphoid (Raji and Daudi) cells...
March 16, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28298211/fty720-inhibits-mesothelioma-growth-in-vitro-and-in-a-syngeneic-mouse-model
#15
Agata Szymiczek, Sandra Pastorino, David Larson, Mika Tanji, Laura Pellegrini, Jiaming Xue, Shuangjing Li, Carlotta Giorgi, Paolo Pinton, Yasutaka Takinishi, Harvey I Pass, Hideki Furuya, Giovanni Gaudino, Andrea Napolitano, Michele Carbone, Haining Yang
BACKGROUND: Malignant mesothelioma (MM) is a very aggressive type of cancer, with a dismal prognosis and inherent resistance to chemotherapeutics. Development and evaluation of new therapeutic approaches is highly needed. Immunosuppressant FTY720, approved for multiple sclerosis treatment, has recently raised attention for its anti-tumor activity in a variety of cancers. However, its therapeutic potential in MM has not been evaluated yet. METHODS: Cell viability and anchorage-independent growth were evaluated in a panel of MM cell lines and human mesothelial cells (HM) upon FTY720 treatment to assess in vitro anti-tumor efficacy...
March 15, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28251149/fibrillar-type-i-collagen-enhances-the-differentiation-and-proliferation-of-myofibroblasts-by-lowering-%C3%AE-2%C3%AE-1-integrin-expression-in-cardiac-fibrosis
#16
Jian Hong, Ming Chu, Lijun Qian, Junhong Wang, Yan Guo, Di Xu
Many studies have shown that α2β1 integrin plays an important role in the development of cardiac fibrosis. However, the mechanism of how α2β1 integrin regulates the differentiation and proliferation of myofibroblasts in cardiac fibrosis through fibrillar collagen (FC) remains uncertain. We established that FC mimicked the 3-dimensional extracellular matrix (ECM) of fibroblasts from post-myocardial infarction (MI) patients in vivo. This allowed us to explore the differentiation and proliferation of cardiac fibroblasts on FC...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28224476/protein-phosphatase-2a-a-double-faced-phosphatase-of-cellular-system-and-its-role-in-neurodegenerative-disorders
#17
REVIEW
Md Nematullah, M N Hoda, Farah Khan
Protein phosphatase 2A (PP2A), a ubiquitously expressed serine/threonine phosphatase, is a vitally important phosphatase for the cellular system. Structurally, it is constituted of three different subunits, namely catalytic subunit (PP2Ac), structural scaffold subunit (PP2A-A), and regulatory subunit (PP2A-B). All subunits have various isoforms, and catalytic and scaffold subunits are ubiquitously expressed, whereas regulatory subunits are more specific to tissue and cell type. It is the numerous possibilities of PP2A holoenzyme assembly with varying isoform components that make it possess a dual nature of activator or the inhibitory character in different signaling pathways, namely neural developmental pathways, Akt/protein kinase B pathway, NF-kB pathway, MAPK pathway, apoptosis pathway, and cell cycle progression to name a few...
February 21, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28222497/correction-lapatinib-inhibits-cip2a-pp2a-p-akt-signaling-and-induces-apoptosis-in-triple-negative-breast-cancer-cells
#18
Chun-Yu Liu, Ming-Hung Hu, Chia-Jung Hsu, Chun-Teng Huang, Duen-Shian Wang, Wen-Chun Tsai, Yi-Ting Chen, Chia-Han Lee, Pei-Yi Chu, Chia-Chi Hsu, Ming-Huang Chen, Chung-Wai Shiau, Ling-Ming Tseng, Kuen-Feng Chen
No abstract text is available yet for this article.
February 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28174209/oncoprotein-cip2a-is-stabilized-via-interaction-with-tumor-suppressor-pp2a-b56
#19
Jiao Wang, Juha Okkeri, Karolina Pavic, Zhizhi Wang, Otto Kauko, Tuuli Halonen, Grzegorz Sarek, Päivi M Ojala, Zihe Rao, Wenqing Xu, Jukka Westermarck
Protein phosphatase 2A (PP2A) is a critical human tumor suppressor. Cancerous inhibitor of PP2A (CIP2A) supports the activity of several critical cancer drivers (Akt, MYC, E2F1) and promotes malignancy in most cancer types via PP2A inhibition. However, the 3D structure of CIP2A has not been solved, and it remains enigmatic how it interacts with PP2A. Here, we show by yeast two-hybrid assays, and subsequent validation experiments, that CIP2A forms homodimers. The homodimerization of CIP2A is confirmed by solving the crystal structure of an N-terminal CIP2A fragment (amino acids 1-560) at 3...
March 2017: EMBO Reports
https://www.readbyqxmd.com/read/28167675/arpp-16-is-a-striatal-enriched-inhibitor-of-protein-phosphatase-2a-regulated-by-microtubule-associated-serine-threonine-kinase-3-mast-3-kinase
#20
Erika C Andrade, Veronica Musante, Atsuko Horiuchi, Hideo Matsuzaki, A Harrison Brody, Terence Wu, Paul Greengard, Jane R Taylor, Angus C Nairn
ARPP-16 (cAMP-regulated phospho-protein of molecular weight 16 kDa) is one of several small acid-soluble proteins highly expressed in medium spiny neurons of striatum that are phosphorylated in response to dopamine acting via D1 receptor/protein kinase A (PKA) signaling. We show here that ARPP-16 is also phosphorylated in vitro and in vivo by microtubule-associated serine/threonine kinase 3 (MAST3 kinase), an enzyme of previously unknown function that is enriched in striatum. We find that ARPP-16 interacts directly with the scaffolding A subunit of the serine/threonine protein phosphatase, PP2A, and that phosphorylation of ARPP-16 at Ser46 by MAST3 kinase converts the protein into a selective inhibitor of B55α- and B56δ-containing heterotrimeric forms of PP2A...
March 8, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
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