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https://www.readbyqxmd.com/read/28430130/timp1-promotes-cell-survival-by-activating-the-pdk1-signaling-pathway-in-melanoma
#1
Mariana Toricelli, Fabiana H M Melo, Aline Hunger, Daniela Zanatta, Bryan E Strauss, Miriam G Jasiulionis
High TIMP1 expression is associated with poor prognosis in melanoma, where it can bind to CD63 and β1 integrin, inducing PI3-kinase pathway and cell survival. Phosphatidylinositol (3,4,5)-trisphosphate (PIP3), generated under phosphatidylinositol-3-kinase (PI3K) activation, enables the recruitment and activation of protein kinase B (PKB/AKT) and phosphoinositide-dependent kinase 1 (PDK1) at the membrane, resulting in the phosphorylation of a host of other proteins. Using a melanoma progression model, we evaluated the impact of Timp1 and AKT silencing, as well as PI3K, PDK1, and protein kinase C (PKC) inhibitors on aggressiveness characteristics...
April 21, 2017: Cancers
https://www.readbyqxmd.com/read/28417590/calcitonin-gene-related-peptide-cgrp-a-novel-target-for-alzheimer-s-disease
#2
REVIEW
Yogendra Singh, Gaurav Gupta, Birendra Shrivastava, Rajiv Dahiya, Juhi Tiwari, Madhu Ashwathanarayana, Rakesh Kumar Sharma, Mohit Agrawal, Anurag Mishra, Kamal Dua
Alzheimer's disease (AD) is leading cause of death among older characterized by neurofibrillary tangles, oxidative stress, progressive neuronal deficits, and increased levels of amyloid-β (Aβ) peptides. Cholinergic treatment could be the best suitable physiological therapy for AD. Calcitonin gene-related peptide (CGRP) is a thirty-seven-amino acid regulatory neuropeptide resulting from different merging of the CGRP gene, which also includes adrenomedullin, amylin, calcitonin, intermedin, and calcitonin receptor-stimulating peptide...
April 17, 2017: CNS Neuroscience & Therapeutics
https://www.readbyqxmd.com/read/28415610/the-tubulin-inhibitor-mg-2477-induces-autophagy-regulated-cell-death-ros-accumulation-and-activation-of-foxo3-in-neuroblastoma
#3
Judith Hagenbuchner, Lorena Lungkofler, Ursula Kiechl-Kohlendorfer, Giampietro Viola, Maria Grazia Ferlin, Michael J Ausserlechner, Petra Obexer
Neuroblastoma is the most frequent extra-cranial solid tumor in children with still high mortality in stage M. Here we studied the tubulin-inhibitor MG-2477 as a possible therapeutic agent for neuroblastoma therapy and uncovered that MG-2477 induces death in neuroblastoma cells independent of PKB-activation status and stage. MG-2477 triggers within 30 minutes extensive autophagosome-formation that finally leads to cell death associated with mitotic catastrophe. Autophagy is critical for MG-2477-induced death and is regulated by the BH3-only protein PMAIP1/NOXA which sequesters the anti-apoptotic BCL2-protein BCLXL and thereby displaces and activates the autophagy-regulator BECN1/beclin1...
March 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28413728/mechanism-of-endothelial-nitric-oxide-synthase-phosphorylation-and-activation-by-tentacle-extract-from-the-jellyfish-cyanea-capillata
#4
Beilei Wang, Dan Liu, Chao Wang, Qianqian Wang, Hui Zhang, Guoyan Liu, Xia Tao, Liming Zhang
Our previous study demonstrated that tentacle extract (TE) from the jellyfish Cyanea capillata (C. capillata) could cause a weak relaxation response mediated by nitric oxide (NO) using isolated aorta rings. However, the intracellular mechanisms of TE-induced vasodilation remain unclear. Thus, this study was conducted to examine the role of TE on Akt/eNOS/NO and Ca(2+) signaling pathways in human umbilical vein endothelial cells (HUVECs). Our results showed that TE induced dose- and time-dependent increases of eNOS activity and NO production...
2017: PeerJ
https://www.readbyqxmd.com/read/28412220/inflammation-induced-glua1-trafficking-and-membrane-insertion-of-ca-2-permeable-ampa-receptors-in-dorsal-horn-neurons-is-dependent-on-spinal-tumor-necrosis-factor-pi3-kinase-and-protein-kinase-a
#5
G Wigerblad, J R Huie, H Z Yin, M Leinders, R A Pritchard, F J Koehrn, W-H Xiao, G J Bennett, R L Huganir, A R Ferguson, J H Weiss, C I Svensson, L S Sorkin
Peripheral inflammation induces sensitization of nociceptive spinal cord neurons. Both spinal tumor necrosis factor (TNF) and neuronal membrane insertion of Ca(2+) permeable AMPA receptor (AMPAr) contribute to spinal sensitization and resultant pain behavior, molecular mechanisms connecting these two events have not been studied in detail. Intrathecal (i.t.) injection of TNF-blockers attenuated paw carrageenan-induced mechanical and thermal hypersensitivity. Levels of GluA1 and GluA4 from dorsal spinal membrane fractions increased in carrageenan-injected rats compared to controls...
April 12, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28405672/glucagon-like-peptide-1-related-peptides-increase-nitric-oxide-effects-to-reduce-platelet-activation
#6
Cristina Barale, Simona Buracco, Franco Cavalot, Chiara Frascaroli, Angelo Guerrasio, Isabella Russo
Glucagon-like peptide 1 (GLP-1) is object of intensive investigation for not only its metabolic effects but also the protective vascular actions. Since platelets exert a primary role in the pathogenesis of atherosclerosis, inflammation and vascular complications, we investigated whether GLP-1 directly influences platelet reactivity. For this purpose, in platelets from 72 healthy volunteers we evaluated GLP-1 receptor (GLP-1R) expression and the effects of a 15-minute incubation with the native form GLP-1(7-36), the N-terminally truncated form GLP-1(9-36) and the GLP-1 analogue Liraglutide (100 nmol/l) on: i) aggregation induced by collagen or arachidonic acid (AA); ii) platelet function under shear stress; iii) cGMP and cAMP synthesis and cGMP-dependent protein kinase (PKG)-induced Vasodilator-Stimulated-Phosphoprotein (VASP) phosphorylation; iv) activation of the signalling molecules Phosphatidylinositol 3-Kinase (PI3-K)/Akt and Mitogen Activated Protein Kinase (MAPK)/ERK-1/2; and v) oxidative stress...
April 13, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28404980/hiv-1-tat-inhibits-eaat-2-through-aeg-1-upregulation-in-models-of-hiv-associated-neurocognitive-disorder
#7
Xiang Ye, Yu Zhang, Qiping Xu, Honghua Zheng, Xiaoyan Wu, Jinhua Qiu, Zhou Zhang, Wei Wang, Yiming Shao, Hui Qin Xing
During HIV-associated neurocognitive disorder (HAND), decreasing in excitatory amino acid transporter 2 (EAAT-2) in astrocyte plasma membranes leads to elevated levels of extracellular glutamate and, in turn, neuronal apoptosis. We used immunohistochemistry, western blot, qRT-PCR, and RNA interference to elucidate the molecular mechanisms underlying the decreased EAAT-2 expression during HAND at the tissue and cellular levels. We used simian immunodeficiency virus-human immunodeficiency virus chimeric virus (SHIV)-infected macaques as an in vivo model of HAND...
March 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28389259/autophagy-induction-by-celastrol-augments-protection-against-bleomycin-induced-experimental-pulmonary-fibrosis-in-rats-role-of-adaptor-protein-p62-sqstm1
#8
Thomas Divya, Anandasadagopan Sureshkumar, Ganapasam Sudhandiran
Pulmonary fibrosis (PF) is a chronic pulmonary disease of unknown cause with high mortality. Autophagy is an important homeostatic process that decides the fate of cells under stress conditions. This study is aimed to investigate whether impaired autophagic activity leads to fibrosis and pharmacological induction of autophagy provides protection against bleomycin (BLM)-induced PF. A single dose of BLM (3 U/kg body weight) was administered intratracheally to induce fibrosis in rats. Celastrol, a triterpenoid (5 mg/kg/body weight, intraperitoneally) was given in every 81 h for a period of 28 days...
April 4, 2017: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28388652/evaluation-of-circulating-mirnas-during-late-pregnancy-in-the-mare
#9
Shavahn C Loux, Kirsten E Scoggin, Jason E Bruemmer, Igor F Canisso, Mats H T Troedsson, Edward L Squires, Barry A Ball
MicroRNAs (miRNAs) are small, non-coding RNAs which are produced throughout the body. Individual tissues tend to have a specific expression profile and excrete many of these miRNAs into circulation. These circulating miRNAs may be diagnostically valuable biomarkers for assessing the presence of disease while minimizing invasive testing. In women, numerous circulating miRNAs have been identified which change significantly during pregnancy-related complications (e.g. chorioamnionitis, eclampsia, recurrent pregnancy loss); however, no prior work has been done in this area in the horse...
2017: PloS One
https://www.readbyqxmd.com/read/28383821/h2-s-induced-gastric-fundus-smooth-muscle-tension-potentiation-is-mediated-by-the-pi3-k-akt-enos-pathway
#10
Xiang-Min Meng, Xu Huang, Hong-Li Lu, Chun-Mei Zhang, Young-Chul Kim, Jie Chen, Wen-Xie Xu
Hydrogen sulfide (H2 S) is considered a new gasotransmitter, along with NO and CO. It was recently confirmed that H2 S and NO play important roles in regulating gastrointestinal smooth muscle tension. The present study was designed to elucidate the interactions between H2 S and NO with respect to gastric fundus smooth muscle tension regulation using western blotting, physiology and electrochemistry techniques. Real-time H2 S and NO generation was detected in gastric smooth muscle tissue. NaHS, an H2 S donor, enhanced fundus smooth muscle tension, while SNP, an NO donor, decreased fundus smooth muscle tension in a dose-dependent manner...
April 6, 2017: Experimental Physiology
https://www.readbyqxmd.com/read/28374141/igf-ii-mediated-downregulation-of-peroxisome-proliferator-activated-receptor-%C3%AE-coactivator-1%C3%AE-in-myoblast-cells-involves-pi3k-akt-foxo1-signaling-pathway
#11
Xiaoyu Mu, Weihong Qi, Yunzhang Liu, Jianfeng Zhou, Yun Li, Xiaozhi Rong, Ling Lu
Insulin-like growth factor II (IGF-II) can stimulate myogenesis and is critically involved in skeletal muscle differentiation. The presence of negative regulators of this process, however, is not well explored. Here, we showed that in myoblast cells, IGF-II negatively regulated peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) mRNA expression, while constitutive expression of PGC-1α induced myoblast differentiation. These results suggest that the negative regulation of PGC-1α by IGF-II may act as a negative feedback mechanism in IGF-II-induced myogenic differentiation...
April 3, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28351565/new-drug-development-in-head-and-neck-squamous-cell-carcinoma-the-pi3-k-inhibitors
#12
REVIEW
Francesca De Felice, Teresa Guerrero Urbano
Over the last few years a number of new different compounds have been developed. They include phosphatidylinositol 3-kinase (PI3-K) inhibitors. Deregulation within the PI3-K pathway is common in head neck squamous cell carcinoma (HNSCC) and it represents a growing area of research. PI3-K inhibitors, including BKM120, PX-866 and BYL719, are being tested in several phase I and phase II studies in patients with locally advanced, recurrent or metastatic disease. This review provides an update of published clinical trials and highlights the challenges of PI3-K inhibitors in HNSCC...
April 2017: Oral Oncology
https://www.readbyqxmd.com/read/28348208/myo6-is-targeted-by-salmonella-virulence-effectors-to-trigger-pi3-kinase-signaling-and-pathogen-invasion-into-host-cells
#13
Andrew B E Brooks, Daniel Humphreys, Vikash Singh, Anthony C Davidson, Susan D Arden, Folma Buss, Vassilis Koronakis
To establish infections, Salmonella injects virulence effectors that hijack the host actin cytoskeleton and phosphoinositide signaling to drive pathogen invasion. How effectors reprogram the cytoskeleton network remains unclear. By reconstituting the activities of the Salmonella effector SopE, we recapitulated Rho GTPase-driven actin polymerization at model phospholipid membrane bilayers in cell-free extracts and identified the network of Rho-recruited cytoskeleton proteins. Knockdown of network components revealed a key role for myosin VI (MYO6) in Salmonella invasion...
March 27, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28335495/brain-derived-neurotrophic-factor-loaded-ps80-pbca-nanocarrier-for-in-vitro-neural-differentiation-of-mouse-induced-pluripotent-stem-cells
#14
Chiu-Yen Chung, Martin Hsiu-Chu Lin, I-Neng Lee, Tsong-Hai Lee, Ming-Hsueh Lee, Jen-Tsung Yang
Brain derived neurotrophic factor (BDNF) can induce neural differentiation in stem cells and has the potential for repair of the nervous system. In this study, a polysorbate 80-coated polybutylcyanoacrylate nanocarrier (PS80 PBCA NC) was constructed to deliver plasmid DNAs (pDNAs) containing BDNF gene attached to a hypoxia-responsive element (HRE-cmvBDNF). The hypoxia-sensing mechanism of BDNF expression and inductiveness of the nano-formulation on mouse induced pluripotent stem cells (iPSCs) to differentiate into neurons following hypoxia was tested in vitro with immunofluorescent staining and Western blotting...
March 19, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28321113/acid-sensing-ion-channel-1a-in-the-amygdala-is-involved-in-pain-and-anxiety-related-behaviours-associated-with-arthritis
#15
Youssef Aissouni, Abderrahim El Guerrab, Al Mahdy Hamieh, Jérémy Ferrier, Maryse Chalus, Diane Lemaire, Stéphanie Grégoire, Monique Etienne, Alain Eschalier, Denis Ardid, Eric Lingueglia, Fabien Marchand
Chronic pain is associated with anxiety and depression episodes. The amygdala plays a key role in the relationship between emotional responses and chronic pain. Here, we investigated the role of Acid-Sensing Ion Channels 1a within the basolateral amygdala (BLA), in pain and associated anxiety in a rat model of monoarthritis (MoAr). Administration within the BLA of PcTx1 or mambalgin-1, two specific inhibitors of ASIC1a-containing channels significantly inhibited pain and anxiety-related behaviours in MoAr rats...
March 2, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28315368/the-emerging-role-of-pi3k-akt-mediated-epigenetic-regulation-in-cancer
#16
REVIEW
Jennifer M Spangle, Thomas M Roberts, Jean J Zhao
The PI3-kinase/AKT pathway integrates signals from external cellular stimuli to regulate essential cellular functions, and is frequently aberrantly activated in human cancers. Recent research demonstrates that tight regulation of the epigenome is critical in preserving and restricting transcriptional activation, which can impact cellular growth and proliferation. In this review we examine mechanisms by which the PI3K/AKT pathway regulates the epigenome to promote oncogenesis, and highlight how connections between PI3K/AKT and the epigenome may impact the future therapeutic treatment of cancers featuring a hyperactivated PI3K/AKT pathway...
March 14, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28306502/pacer-mediates-the-function-of-class-iii-pi3k-and-hops-complexes-in-autophagosome-maturation-by-engaging-stx17
#17
Xiawei Cheng, Xiuling Ma, Xianming Ding, Lin Li, Xiao Jiang, Zhirong Shen, She Chen, Wei Liu, Weihua Gong, Qiming Sun
Class III PI3-kinase (PI3KC3) is essential for autophagy initiation, but whether PI3KC3 participates in other steps of autophagy remains unknown. The HOPS complex mediates the fusion of intracellular vesicles to lysosome, but how HOPS specifically tethers autophagosome to lysosome remains elusive. Here, we report Pacer (protein associated with UVRAG as autophagy enhancer) as a regulator of autophagy. Pacer localizes to autophagic structures and positively regulates autophagosome maturation. Mechanistically, Pacer antagonizes Rubicon to stimulate Vps34 kinase activity...
March 16, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28303260/evidence-for-an-additive-neurorestorative-effect-of-simultaneously-administered-cdnf-and-gdnf-in-hemiparkinsonian-rats-implications-for-different-mechanism-of-action
#18
Merja H Voutilainen, Francesca De Lorenzo, Polina Stepanova, Susanne Bäck, Li-Ying Yu, Päivi Lindholm, Eeva Pörsti, Mart Saarma, Pekka T Männistö, Raimo K Tuominen
Parkinson's disease (PD) is a neurodegenerative disorder associated with a progressive loss of dopaminergic (DAergic) neurons of the substantia nigra (SN) and the accumulation of intracellular inclusions containing α-synuclein. Current therapies do not stop the progression of the disease, and the efficacy of these treatments wanes over time. Neurotrophic factors (NTFs) are naturally occurring proteins promoting the survival and differentiation of neurons and the maintenance of neuronal contacts. CDNF (cerebral dopamine NTF) and GDNF (glial cell line-derived NTF) are able to protect DAergic neurons against toxin-induced degeneration in experimental models of PD...
January 2017: ENeuro
https://www.readbyqxmd.com/read/28302666/mtorc1-signalling-mediates-pi3k-dependent-large-lipid-droplet-accumulation-in-drosophila-ovarian-nurse-cells
#19
Lawrence B Mensah, Deborah C I Goberdhan, Clive Wilson
Insulin and insulin-like growth factor signalling (IIS), which is primarily mediated by the PI3-kinase (PI3K)/PTEN/Akt kinase signalling cassette, is a highly evolutionary conserved pathway involved in co-ordinating growth, development, ageing and nutrient homeostasis with dietary intake. It controls transcriptional regulators, in addition to promoting signalling by mechanistic Target of Rapamycin (mTOR) Complex 1 (mTORC1), which stimulates biosynthesis of proteins and other macromolecules, and drives organismal growth...
March 16, 2017: Biology Open
https://www.readbyqxmd.com/read/28291540/roux-en-y-gastric-bypass-improves-glucose-homeostasis-reduces-oxidative-stress-and-inflammation-in-livers-of-obese-rats-and-in-kupffer-cells-via-an-ampk-dependent-pathway
#20
Yanhua Peng, James Zongyu Li, Min You, Michel M Murr
BACKGROUND: Oxidative stress and inflammation are implicated in the pathogenesis of steatohepatitis. We hypothesize that Roux-en-Y gastric bypass reduces oxidative stress and inflammation in the liver of obese rats via activation of AMPK-α. METHODS: Obese Sprague-Dawley male rats underwent either sham operation or Roux-en-Y gastric bypass. Hepatic TNF-α, NF-κB, IRS-2, PI3 kinase, PKC-ζ, NOX2, and AMPK-α were measured. Mechanistic studies were done in a rat Kupffer cell line (RKC1) that was treated with free fatty acids to mimic lipotoxicity and then transfected with AMPK-α siRNA...
March 10, 2017: Surgery
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