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https://www.readbyqxmd.com/read/29021338/a-daple-akt-feed-forward-loop-enhances-non-canonical-wnt-signals-by-compartmentalizing-%C3%AE-catenin
#1
Nicolas Aznar, Nina Sun, Ying Dunkel, Jason Ear, Matthew D Buschman, Pradipta Ghosh
Cellular proliferation is antagonistically regulated by canonical and non-canonical Wnt signals; their dysbalance triggers cancers. We previously showed that a multimodular signal transducer, Daple, enhances PI3-K→Akt signals within the non-canonical Wnt signaling pathway and antagonistically inhibits canonical Wnt responses. Here we demonstrate that the PI3-K→Akt pathway serves as a positive feedback loop that further enhances non-canonical Wnt signals by compartmentalizing β-catenin. By phosphorylating the phosphoinositide(PI)-binding domain of Daple, Akt abolishes Daple's ability to bind PI3-P-enriched endosomes that engage dynein motor complex for long-distance trafficking of β-catenin/E-cadherin complexes to pericentriolar recycling endosomes (PCREs)...
October 11, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28993461/brucella-abortus-promotes-a-fibrotic-phenotype-in-hepatic-stellate-cells-with-concomitant-autophagy-pathway-activation
#2
Paula Constanza Arriola Benitez, Ayelén Ivana Pesce Viglietti, Claudia Karina Herrmann, Vida A Dennis, Diego José Comerci, Guillermo Hernán Giambartolomei, María Victoria Delpino
The liver is frequently affected in patients with active brucellosis. The present study demonstrates that B. abortus infection induces the activation of the autophagic pathway in hepatic stellate cells to create a microenvironment that promote a profibrogenic phenotype through the induction of transforming growth factor-β1 (TGF-β1), collagen deposition and inhibition of matrix metalloproteinase-9 (MMP-9) secretion. Autophagy was revealed by up-regulation of the LC3II/LC3I ratio and beclin-1 expression as well as inhibition of p62 expression in infected cells...
October 9, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28983020/ekert-pg-jabbour-am-manoharan-a-et-al-cell-death-provoked-by-loss-of-interleukin-3-signaling-is-independent-of-bad-bim-and-pi3-kinase-but-depends-in-part-on-puma-blood-2006-108-5-1461-1468
#3
https://www.readbyqxmd.com/read/28978065/the-pan-bcl-2-blocker-obatoclax-gx15-070-and-the-pi3-kinase-mtor-inhibitor-bez235-produce-cooperative-growth-inhibitory-effects-in-all-cells
#4
Gabriele Stefanzl, Daniela Berger, Sabine Cerny-Reiterer, Katharina Blatt, Gregor Eisenwort, Wolfgang R Sperr, Gregor Hoermann, Karin Lind, Alexander W Hauswirth, Peter Bettelheim, Heinz Sill, Junia V Melo, Ulrich Jäger, Peter Valent
Acute lymphoblastic leukemia (ALL) is characterized by leukemic expansion of lymphoid blasts in hematopoietic tissues. Despite improved therapy only a subset of patients can be cured. Therefore, current research is focusing on new drug-targets. Members of the BCL-2 family and components of the PI3-kinase/mTOR pathway are critically involved in the regulation of growth and survival of ALL cells. We examined the effects of the pan-BCL-2 blocker obatoclax and the PI3-kinase/mTOR-inhibitor BEZ235 on growth and survival of ALL cells...
September 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28973876/critical-role-for-pi3-kinase-in-regulating-the-use-of-proteins-as-an-amino-acid-source
#5
Wilhelm Palm, Jingwen Araki, Bryan King, Raymond G DeMatteo, Craig B Thompson
Ras-transformed cells can grow in amino acid-poor environments by recovering amino acids through macropinocytosis and lysosomal catabolism of extracellular proteins. However, when studying nontransformed fibroblasts, we found that Ras GTPases are dispensable for growth-factor-stimulated macropinocytosis and lysosomal catabolism of extracellular proteins. Instead, we establish a critical role for phosphatidylinositol 3-kinase (PI3-kinase) signaling in cell proliferation that is supported by protein macropinocytosis...
September 25, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28971334/preventive-effect-of-oleate-on-palmitate-induced-insulin-resistance-in-skeletal-muscle-and-its-mechanism-of-action
#6
Hakam Alkhateeb, Esam Qnais
Insulin resistance in skeletal muscle is a feature associated with exposure to an excess of saturated fatty acids such as palmitate. Oleic acid has been shown to blunt palmitate-induced insulin resistance in muscle cells. However, there is no literature available regarding the effect of oleic acid on palmitate-induced insulin resistance in intact muscle. Therefore, this study investigated the effect of oleic acid on palmitate-induced insulin resistance in rat soleus muscle and its underlying mechanisms. For these purposes, oleic acid (1 mM) was administered for 12 h in the absence or presence of palmitate (2 mM)...
October 3, 2017: Journal of Physiology and Biochemistry
https://www.readbyqxmd.com/read/28969943/deciphering-the-pathways-that-protect-from-il-13-mediated-potentiation-of-oxidative-stress-induced-dopaminergic-nerve-cell-death
#7
Pamela Maher, Bruno Conti
The majority of Parkinson's disease (PD) cases are sporadic with only about 10% of PD patients having a family history of the disease suggesting that this neurodegenerative disorder is the result of both environmental and genetic factors. Both oxidative stress and neuroinflammation are thought to contribute to PD. Previously, we showed that the activation of interleukin 13 receptor alpha 1 (IL-13Rα1) increases the sensitivity of dopaminergic neurons to oxidative damage both in cultured cells and in animals...
September 30, 2017: Cytokine
https://www.readbyqxmd.com/read/28969040/tripchlorolide-induces-autophagy-in-lung-cancer-cells-by-inhibiting-the-pi3k-akt-mtor-pathway-and-improves-cisplatin-sensitivity-in-a549-ddp-cells
#8
Li-Min Chen, Tian-Jiao Song, Jian-Hong Xiao, Zheng-Hui Huang, Yong Li, Ting-Yan Lin
Tripchlorolide (T4) has been shown to induce A549 lung cancer cell death predominantly by activating an autophagy pathway. However, the underlying mechanism remains unclear. Herein, we demonstrated that compared with T4 treatment alone, pretreatment with wortmannin (an inhibitor of phosphatidylinositol 3-kinase), perifosine (an inhibitor of AKT) or rapamycin (an inhibitor of mTOR) combined with a subsequent T4 treatment significantly impaired the cell viability of A549 and A549/DDP lung cancer cells. We found that either treatment scheme markedly reduced the activity of P13K and AKT...
September 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28966111/cationic-liposomes-suppress-intracellular-calcium-ion-concentration-increase-via-inhibition-of-pi3-kinase-pathway-in-mast-cells
#9
Yoshikazu Inoh, Aki Haneda, Satoshi Tadokoro, Satoru Yokawa, Tadahide Furuno
Cationic liposomes are commonly used as vectors to effectively introduce foreign genes (antisense DNA, plasmid DNA, siRNA, etc.) into target cells. Cationic liposomes are also known to affect cellular immunocompetences such as the mast cell function in allergic reactions. In particular, we previously showed that the cationic liposomes bound to the mast cell surface suppress the degranulation induced by cross-linking of high affinity IgE receptors in a time- and dose-dependent manner. This suppression is mediated by impairment of the sustained level of intracellular Ca(2+) concentration ([Ca(2+)]i) via inhibition of store-operated Ca(2+) entry (SOCE)...
September 29, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28965266/periostin-silencing-suppresses-the-aggressive-phenotype-of-thyroid-carcinoma-cells-by-suppressing-the-akt-thyroid-stimulating-hormone-receptor-axis
#10
Min Wang, Chunyi Gui, Shenglong Qiu, Jingdong Tang, Zhihai Peng
Clinical evidence indicates that high periostin expression correlates with aggressive phenotype in thyroid carcinoma. However, the biological roles of periostin in thyroid carcinoma development and progression are still unclear. In this study, we explored the effects of periostin silencing on thyroid carcinoma cell growth, invasion, and tumorigenesis. We also studied the impact of periostin on the activation of phosphoinositide 3-kinase (PI3-K)/Akt signaling, which is involved in the pathogenesis of thyroid carcinoma...
September 30, 2017: Cytotechnology
https://www.readbyqxmd.com/read/28962111/microrna-138-suppresses-cell-proliferation-in-laryngeal-squamous-cell-carcinoma-via-inhibiting-ezh2-and-pi3k-akt-signaling
#11
Fengzhi Si, Jie Sun, Chunli Wang
MicroRNA (miR)-138 generally has a suppressive role in various human cancer types; however, its role and the underlying mechanisms in laryngeal squamous cell carcinoma (LSCC) have remained to be elucidated. The present study assessed the clinical significance and regulatory mechanisms of miR-138 in LSCC progression. Reverse-transcription quantitative polymerase chain reaction analysis indicated that miR-138 was significantly downregulated in LSCC tissues and cell lines. In addition, the decreased expression of miR-138 was significantly associated with poor differentiation, lymph node metastasis and advanced clinical stage of LSCC...
September 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28960620/igf-1-promotes-angiogenesis-in-endothelial-cells-adipose-derived-stem-cells-co-culture-system-with-activation-of-pi3k-akt-signal-pathway
#12
Shiyu Lin, Qi Zhang, Xiaoru Shao, Tao Zhang, Changyue Xue, Sirong Shi, Dan Zhao, Yunfeng Lin
OBJECTIVES: The aim of this study was to investigate the role of insulin-like growth factor-1 (IGF-1) and crosstalk between endothelial cells (ECs) and adipose-derived stem cells (ASCs) in the process of angiogenesis. METHODS: A three-dimensional collagen gel used to culture mouse ASCs and mouse ECs in vitro was established. The effects of angiogenesis after exposure to IGF-1 were observed by confocal laser scanning microscopy. Western blotting and qPCR were performed to elucidate the underlying mechanisms...
September 27, 2017: Cell Proliferation
https://www.readbyqxmd.com/read/28956013/fluid-shear-stress-applied-by-orbital-shaking-induces-mg-63-osteosarcoma-cells-to-activate-erk-in-two-phases-through-distinct-signaling-pathways
#13
Takashi Fukada, Hiroki Sakajiri, Mito Kuroda, Noriyuki Kioka, Kenji Sugimoto
Fluid shear stress (FSS) induces a series of biochemical responses in osteoblasts, and this "mechanoresponse" regulates their survival, proliferation and differentiation. However, the events in cells immediately after FSS application are unclear, and how biochemical signals from soluble factors modify the mechanoresponses is largely unknown. We used the orbital shaking method, instead of the frequently used parallel plate method, to examine activation of ERK and AKT by FSS for detailed tracking of its temporal transition...
March 2017: Biochemistry and Biophysics Reports
https://www.readbyqxmd.com/read/28955964/effect-of-n-arachidonoyl-l-serine-on-human-cerebromicrovascular-endothelium
#14
Tomoyuki Kino, Toshiki Tomori, Rania Abutarboush, Paola Castri, Ye Chen, Frederick A Lenz, Richard M McCarron, Maria Spatz
N-arachidonoyl-l-serine (ARA-S) is an endogenous lipid, chemically related to the endocannabinoid, N-arachidonoyl ethanolamine (i.e., anandamide) and with similar physiologic and pathophysiologic functions. Reports indicate that ARA-S possesses vasoactive and neuroprotective properties resembling those of cannabinoids. However, in contrast to cannabinoids, ARA-S binds weakly to its known classical receptors, CB1 and CB2, and is therefore considered to be a 'cannabinoid-like' substance. The originally described ARA-S induced-endothelial-dependent vasorelaxation was not abrogated by CB1, CB2 receptor antagonists or TRPV1 competitive inhibitor...
December 2016: Biochemistry and Biophysics Reports
https://www.readbyqxmd.com/read/28938529/defining-a-therapeutic-window-for-kinase-inhibitors-in-leukemia-to-avoid-neutropenia
#15
Kate McArthur, Akshay A D'Cruz, David Segal, Kurt Lackovic, Andrew F Wilks, Joanne A O'Donnell, Cameron J Nowell, Motti Gerlic, David C S Huang, Christopher J Burns, Ben A Croker
Neutropenia represents one of the major dose-limiting toxicities of many current cancer therapies. To circumvent the off-target effects of cytotoxic chemotherapeutics, kinase inhibitors are increasingly being used as an adjunct therapy to target leukemia. In this study, we conducted a screen of leukemic cell lines in parallel with primary neutrophils to identify kinase inhibitors with the capacity to induce apoptosis of myeloid and lymphoid cell lines whilst sparing primary mouse and human neutrophils. We have utilized a high-throughput live cell imaging platform to demonstrate that cytotoxic drugs have limited effects on neutrophil viability but are toxic to hematopoietic progenitor cells, with the exception of the topoisomerase I inhibitor SN-38...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28936851/-research-of-reversal-effect-of-pesv-to-multi-drug-resistance-of-leukemia-stem-cell
#16
Xiang-Dong Yang, Xing-Li Wang, Wen-Hua Yang, Lei Zhao, Tian-Gai Yan
Using the BALB/c mouse multidrug resistance model of leukemia, the effect of peptide extract from scorpion venom (PESV) to the upstream signal factors of P-gp of MDR leukemia stem cells on the mouse tumor block was observed, and the mechanism of PESV to reverse the MDR of LSC was studied. At the same time, the expression of P-gp, MDR1 mRNA and PI3-K, NF-κB were respectively detected through flow cytometry, RT-PCR, Western blot and Elisa, and the mouse liver, spleen were examined via histopathological methods...
December 2016: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
https://www.readbyqxmd.com/read/28930961/impact-of-a-novel-phosphoinositol-3-kinase-inhibitor-in-preventing-mitochondrial-dna-damage-and-damage-associated-molecular-pattern-accumulation-results-from-the-biochronicity-project
#17
George Edward Black, Kyle K Sokol, Donald M Moe, Jon D Simmons, David Muscat, Victor Pastukh, Gina Capley, Olena Gorodnya, Mykhaylo Ruchko, Mark B Roth, Mark Gillespie, Matthew J Martin
BACKGROUND: Despite improvements in the management of severely injured patients, development of multiple organ dysfunction syndrome (MODS) remains a morbid complication of traumatic shock. One of the key attributes of MODS is a profound bioenergetics crisis, for which the mediators and mechanisms are poorly understood. We hypothesized that metabolic uncoupling using an experimental phosphoinositol-3 kinase (PI3-K) inhibitor, LY294002 (LY), may prevent mitochondrial abnormalities that lead to the generation of mitochondrial DNA (mtDNA) damage and the release of mtDNA damage-associated molecular patterns (DAMPs)...
October 2017: Journal of Trauma and Acute Care Surgery
https://www.readbyqxmd.com/read/28912810/latent-inflammation-and-insulin-resistance-in-adipose-tissue
#18
REVIEW
I S Stafeev, A V Vorotnikov, E I Ratner, M Y Menshikov, Ye V Parfyonova
Obesity is a growing problem in modern society and medicine. It closely associates with metabolic disorders such as type 2 diabetes mellitus (T2DM) and hepatic and cardiovascular diseases such as nonalcoholic fatty liver disease, atherosclerosis, myocarditis, and hypertension. Obesity is often associated with latent inflammation; however, the link between inflammation, obesity, T2DM, and cardiovascular diseases is still poorly understood. Insulin resistance is the earliest feature of metabolic disorders. It mostly develops as a result of dysregulated insulin signaling in insulin-sensitive cells, as compared to inactivating mutations in insulin receptor or signaling proteins that occur relatively rare...
2017: International Journal of Endocrinology
https://www.readbyqxmd.com/read/28903400/hyperglycemia-and-advanced-glycation-end-products-ages-suppress-the-differentiation-of-3t3-l1-preadipocytes
#19
Chia-Chu Chang, Chen-Yu Chen, Geen-Dong Chang, Ting-Huan Chen, Woan-Ling Chen, Hui-Chin Wen, Chih-Yang Huang, Chung-Ho Chang
Aging is characterized by mild hyperglycemia and accumulation of advanced glycation end products (AGEs). Effects of chronic exposure to hyperglycemia or AGEs on the adipogenic differentiation of 3T3-L1 preadipocytes remain unclear. We examined the chronic effect of AGEs and high glucose on the differentiation of 3T3-L1 cells by culturing 3T3-L1 cells in the presence of AGEs or 25 mM glucose for 1 month. Chronic incubation of 3T3-L1 cells with AGEs or high glucose blocked their differentiation into mature adipocytes as evidenced by reduced levels of adipocyte markers such as accumulated oil droplets, GPDH, aP2, adiponectin and of adipogenesis regulators PPARγ and C/EBPα...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28893228/xiap-over-expression-is-an-independent-poor-prognostic-marker-in-middle-eastern-breast-cancer-and-can-be-targeted-to-induce-efficient-apoptosis
#20
Azhar R Hussain, Abdul Khalid Siraj, Maqbool Ahmed, Rong Bu, Poyil Pratheeshkumar, Alanood M Alrashed, Zeeshan Qadri, Dahish Ajarim, Fouad Al-Dayel, Shaham Beg, Khawla S Al-Kuraya
BACKGROUND: Breast cancer is the most common cancer in females and is ranked second in cancer-related deaths all over the world in women. Despite improvement in diagnosis, the survival rate of this disease has still not improved. X-linked Inhibitor of Apoptosis (XIAP) has been shown to be over-expressed in various cancers leading to poor overall survival. However, the role of XIAP in breast cancer from Middle Eastern region has not been fully explored. METHODS: We examined the expression of XIAP in more than 1000 Middle Eastern breast cancer cases by immunohistochemistry...
September 11, 2017: BMC Cancer
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