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https://www.readbyqxmd.com/read/27906453/syk-inhibition-blocks-airway-constriction-and-protects-from-th2-induced-airway-inflammation-and-remodeling-in-mice
#1
Christoph Tabeling, Julia Herbert, Andreas C Hocke, David Lamb, Lutz Wollin, Klaus Erb, Ekaterina Boiarina, Hesam Movassagh, Jörg Scheffel, Jan M Doehn, Stefan Hippenstiel, Marcus Maurer, Abdelilah S Gounni, Wolfgang M Kuebler, Norbert Suttorp, Martin Witzenrath
BACKGROUND: Spleen tyrosine kinase (Syk) is an intracellular non-receptor tyrosine kinase, which has been implicated as central immune modulator promoting allergic airway inflammation. Syk inhibition has been proposed as a new therapeutic approach in asthma. However, the direct effects of Syk inhibition on airway constriction independent of allergen sensitization remain elusive. METHODS: Spectral confocal microscopy of human and murine lung tissue was performed to localize Syk expression...
December 1, 2016: Allergy
https://www.readbyqxmd.com/read/27903982/m2-like-tumor-associated-macrophages-drive-vasculogenic-mimicry-through-amplification-of-il-6-expression-in-glioma-cells
#2
Lin Zhang, Yangyang Xu, Jintang Sun, Weiliang Chen, Lei Zhao, Chao Ma, Qingjie Wang, Jia Sun, Bin Huang, Yun Zhang, Xingang Li, Xun Qu
Vasculogenic mimicry (VM) has offered a new horizon for understanding tumor angiogenesis, but the mechanisms of VM in glioma progression have not been studied explicitly until now. As a significant component of immune infiltration in tumor microenvironment, macrophages have been demonstrated to play an important role in tumor growth and angiogenesis. However, whether macrophages could play a potential key role in glioma VM is still poorly understood. Herein we reported that both VM and CD163+ cells were associated with WHO grade and reduced patient survival, and VM channel counting was correlated to the number of infiltrated CD163+ cells in glioma specimens...
November 26, 2016: Oncotarget
https://www.readbyqxmd.com/read/27903584/src-independent-erk-signaling-through-the-%C3%AE-3-isoform-of-na-k-atpase
#3
Namrata Madan, Yunhui Xu, Qiming Duan, Moumita Banerjee, Isabel Larre, Sandrine V Pierre, Zijian Xie
The Na/K-ATPase α1 polypeptide supports both ion pumping and signaling functions. The Na/K-ATPase α3 polypeptide differs from α1 in both its primary structure and its tissue distribution. Alpha3 expression seems particularly important in neurons, and recent clinical evidence supports a unique role of this isoform in normal brain function. The nature of this specific role of α3 has remained elusive, because the ubiquitous presence of α1 has hindered efforts to characterize α3-specific functions in mammalian cell systems...
November 30, 2016: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/27903111/electric-stimulation-enhances-cardiac-differentiation-of-human-induced-pluripotent-stem-cells-for-myocardial-infarction-therapy
#4
Ruilian Ma, Jialiang Liang, Wei Huang, Linlin Guo, WenFeng Cai, Lei Wang, Christian Paul, Huang-Tian Yang, Ha Won Kim, Yigang Wang
AIM: Electrical stimulation (EleS) can promote cardiac differentiation, but the underlying mechanism is not well known. This study investigated the effect of EleS on cardiomyocyte (CM) differentiation of human induced pluripotent stem cells (hiPSCs) and evaluated the therapeutic effects for the treatment of myocardial infarction (MI). RESULTS: Cardiac differentiation of hiPSCs was induced with EleS after embryoid body formation. Spontaneously beating hiPSCs were observed as early at 2 days when treated with EleS as compared to control treatment...
November 30, 2016: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/27902483/androgen-receptor-phosphorylation-status-at-serine-578-predicts-poor-outcome-in-prostate-cancer-patients
#5
Patek Sc, Willder Jm, Heng Js, Taylor B, Horgan Pg, Leung Hy, Underwood Ma, Edwards J
PURPOSE: Prostate cancer growth is dependent upon androgen receptor (AR) activation, regulated via phosphorylation. Protein kinase C (PKC) is one kinase that can mediate AR phosphorylation. This study aimed to establish if AR phosphorylation by PKC is of prognostic significance. METHODS: Immunohistochemistry for AR, AR phosphorylated at Ser-81 (pARS81), AR phosphorylated at Ser-578 (pARS578), PKC and phosphorylated PKC (pPKC) was performed on 90 hormone-naïve prostate cancer specimens...
November 25, 2016: Oncotarget
https://www.readbyqxmd.com/read/27901058/a-kinase-anchoring-protein-4-akap4-is-an-erk1-2-substrate-and-a-switch-molecule-between-camp-pka-and-pkc-erk1-2-in-human-spermatozoa
#6
Liat Rahamim Ben-Navi, Tal Almog, Zhong Yao, Rony Seger, Zvi Naor
Mammalian spermatozoa undergo capacitation and acrosome reaction in order to fertilize the egg. The PKC-ERK1/2 pathway plays an important role in human spermatozoa motility, capacitation and the acrosome reaction. Here we demonstrate that ERK1/2 phosphorylates proAKAP4 on Thr265 in human spermatozoa in vitro and in vivo. Cyclic AMP (cAMP) had no effect on ERK1/2 activity in human spermatozoa, but stimulated the MAPK in mouse pituitary LβT2 gonadotrope cells. cAMP via PKA attenuates PKC-dependent ERK1/2 activation only in the presence of proAKAP4...
November 30, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27899278/benznidazole-the-trypanocidal-drug-used-for-chagas-disease-induces-hepatic-nrf2-activation-and-attenuates-the-inflammatory-response-in-a-murine-model-of-sepsis
#7
Flavia Lambertucci, Omar Motiño, Silvina Villar, Juan Pablo Rigalli, María de Luján Alvarez, Viviana Catania, Paloma Martín-Sanz, Cristina Ester Carnovale, Ariel Darío Quiroga, Daniel Eleazar Francés, María Teresa Ronco
Molecular mechanisms on sepsis progression are linked to the imbalance between reactive oxygen species (ROS) production and cellular antioxidant capacity. Previous studies demonstrated that benznidazole (BZL), known for its antiparasitic action on Trypanosoma cruzi, has immunomodulatory effects, increasing survival in C57BL/6 mice in a model of polymicrobial sepsis induced by cecal ligation puncture (CLP). The mechanism by which BZL inhibits inflammatory response in sepsis is poorly understood. Also, our group recently reported that BZL is able to activate the nuclear erythroid 2-related factor 2 (NRF2) in vitro...
November 26, 2016: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/27896650/neuroprotection-by-chlorpromazine-and-promethazine-in-severe-transient-and-permanent-ischemic-stroke
#8
Xiaokun Geng, Fengwu Li, James Yip, Changya Peng, Omar Elmadhoun, Jiamei Shen, Xunming Ji, Yuchuan Ding
Previous studies have demonstrated depressive or hibernation-like roles of phenothiazine neuroleptics [combined chlorpromazine and promethazine (C + P)] in brain activity. This ischemic stroke study aimed to establish neuroprotection by reducing oxidative stress and improving brain metabolism with post-ischemic C + P administration. Sprague-Dawley rats were subjected to transient (2 or 4 h) middle cerebral artery occlusion (MCAO) followed by 6 or 24 h reperfusion, or permanent (28 h) MCAO without reperfusion...
November 28, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27895670/wnt5a-increases-properties-of-lung-cancer-stem-cells-and-resistance-to-cisplatin-through-activation-of-wnt5a-pkc-signaling-pathway
#9
Jiali Yang, Kangjian Zhang, Jing Wu, Juan Shi, Jing Xue, Jing Li, Juan Chen, Yongzhao Zhu, Jun Wei, Jinxi He, Xiaoming Liu
The development of chemoresistance to cisplatin regimens causes a poor prognosis in patients with advanced NSCLC. The role of noncanonical Wnt signaling in the regulation of properties of lung cancer stem cells and chemoresistance was interrogated, by accessing capacities of cell proliferation, migration, invasion, and clonogenicity as well as the apoptosis in A549 cell lines and cisplatin-resistant A549 cells treated with Wnt5a conditional medium or protein kinase C (PKC) inhibitor GF109203X. Results showed that the noncanonical Wnt signaling ligand, Wnt5a, could promote the proliferation, migration, invasion, and colony formation in A549 lung adenocarcinoma cells and cisplatin-resistant A549/DDP cells and increase the fraction of ALDH-positive cell in A549/DDP cells...
2016: Stem Cells International
https://www.readbyqxmd.com/read/27895577/fus1-ko-mouse-as-a-model-of-oxidative-stress-mediated-sporadic-alzheimer-s-disease-circadian-disruption-and-long-term-spatial-and-olfactory-memory-impairments
#10
Guillermo Coronas-Samano, Keeley L Baker, Winston J T Tan, Alla V Ivanova, Justus V Verhagen
Insufficient advances in the development of effective therapeutic treatments of sporadic Alzheimer's Disease (sAD) to date are largely due to the lack of sAD-relevant animal models. While the vast majority of models do recapitulate AD's hallmarks of plaques and tangles by virtue of tau and/or beta amyloid overexpression, these models do not reflect the fact that in sAD (unlike familial AD) these genes are not risk factors per se and that other mechanisms like oxidative stress, metabolic dysregulation and inflammation play key roles in AD etiology...
2016: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/27893829/sansevieria-roxburghiana-schult-schult-f-family-asparagaceae-attenuates-type-2-diabetes-and-its-associated-cardiomyopathy
#11
Niloy Bhattacharjee, Ritu Khanra, Tarun K Dua, Susmita Das, Bratati De, M Zia-Ul-Haq, Vincenzo De Feo, Saikat Dewanjee
BACKGROUND: Sansevieria roxburghiana Schult. & Schult. F. (Family: Asparagaceae) rhizome has been claimed to possess antidiabetic activity in the ethno-medicinal literature in India. Therefore, present experiments were carried out to explore the protective role of edible (aqueous) extract of S. roxburghiana rhizome (SR) against experimentally induced type 2 diabetes mellitus (T2DM) and its associated cardiomyopathy in Wistar rats. METHODS: SR was chemically characterized by GC-MS analysis...
2016: PloS One
https://www.readbyqxmd.com/read/27890559/fluoxetine-and-its-active-metabolite-norfluoxetine-disrupt-estrogen-synthesis-in-a-co-culture-model-of-the-feto-placental-unit
#12
Andrée-Anne Hudon Thibeault, Laetitia Laurent, Sung Vo Duy, Sébastien Sauvé, Patrick Caron, Chantal Guillemette, J Thomas Sanderson, Cathy Vaillancourt
The effects of fluoxetine, one of the most prescribed selective serotonin-reuptake inhibitors (SSRIs) during pregnancy, and its active metabolite norfluoxetine were studied on placental aromatase (CYP19) and feto-placental steroidogenesis Fluoxetine did not alter estrogen secretion in co-culture of fetal-like adrenocortical (H295R) and trophoblast-like (BeWo) cells used as a model of the feto-placental unit, although it induced CYP19 activity, apparently mediated by the serotonin (5-HT) 2A receptor/PKC signalling pathway...
November 24, 2016: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/27889530/identification-of-proximal-biomarkers-of-pkc-agonism-and-evaluation-of-their-role-in-hiv-reactivation
#13
Sai Vikram Vemula, Jill W Maxwell, Alexey Nefedov, Bang-Lin Wan, Justin Steve, William Newhard, Rosa I Sanchez, David Tellers, Richard J Barnard, Wade Blair, Daria Hazuda, Andrea L Webber, Bonnie J Howell
DESIGN: The HIV latent CD4(+) T cell reservoir is broadly recognized as a barrier to HIV cure. Induction of HIV expression using protein kinase C (PKC) agonists is one approach under investigation for reactivation of latently infected CD4(+) T cells (Beans et al., 2013; Abreu et al., 2014; Jiang et al., 2014; Jiang and Dandekar, 2015). We proposed that an increased understanding of the molecular mechanisms of action of PKC agonists was necessary to inform on biological signaling and pharmacodynamic biomarkers...
November 23, 2016: Antiviral Research
https://www.readbyqxmd.com/read/27882945/adiponectin-reduces-er-stress-induced-apoptosis-through-ppar%C3%AE-transcriptional-regulation-of-atf2-in-mouse-adipose
#14
Zhenjiang Liu, Lu Gan, Tianjiao Wu, Fei Feng, Dan Luo, Huihui Gu, Shimin Liu, Chao Sun
Adiponectin is a cytokine produced predominantly by adipose tissue and correlates with glucose and lipid homeostasis. However, the effects of adiponectin on endoplasmic reticulum (ER) stress and apoptosis of adipose tissue remain elusive. In this study, we found that tunicamycin-induced ER stress increased serum free fatty acid (FFA) and impaired glucose tolerance, elevated the mRNA levels of GRP78, Chop, ATF2 and caspase 3, but reduced adiponectin mRNA level in white adipose tissue. Moreover, ER stress-triggered adipocyte apoptosis by increasing cellular FFA level and Ca(2+) level...
November 24, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27876895/multiple-crosstalk-between-tor-and-the-cell-integrity-mapk-signaling-pathway-in-fission-yeast
#15
Marisa Madrid, Beatriz Vázquez-Marín, Alejandro Franco, Teresa Soto, Jero Vicente-Soler, Mariano Gacto, José Cansado
In eukaryotic cells, the highly conserved Target of Rapamycin (TOR) and the Mitogen Activated Protein Kinase (MAPK) signaling pathways elicit adaptive responses to extra- and intracellular conditions by regulating essential cellular functions. However, the nature of the functional relationships between both pathways is not fully understood. In the fission yeast Schizosaccharomyces pombe the cell integrity MAPK pathway (CIP) regulates morphogenesis, cell wall structure and ionic homeostasis. We show that the Rab GTPase Ryh1, a TORC2 complex activator, cross-activates the CIP and its core member, the MAPK Pmk1, by two distinct mechanisms...
November 23, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27876620/the-gabab-positive-allosteric-modulators-cgp7930-and-gs39783-stimulate-erk1-2-signalling-in-cells-lacking-functional-gabab-receptors
#16
Maria C Olianas, Simona Dedoni, Pierluigi Onali
The present study shows that the GABAB positive allosteric modulators (PAMs) CGP7930 and GS39783 stimulate extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) signalling in cells that do not express functional GABAB receptors. In human SH-SY5Y neuroblastoma cells, CGP7930 and GS39783 induced a time- and concentration-dependent increase in ERK1/2 phosphorylation with potencies similar to those displayed as GABAB PAMs. Conversely, γ-aminobutyric acid and the GABAB receptor agonists (-)baclofen and SKF97541 were completely inactive...
November 19, 2016: European Journal of Pharmacology
https://www.readbyqxmd.com/read/27874143/total-synthesis-of-natural-derivatives-and-artificial-analogs-of-13-oxyingenol-and-their-biological-evaluation
#17
Takayuki Ohyoshi, Yuki Tamura, Ichiro Hayakawa, Go Hirai, Yamato Miyazawa, Shota Funakubo, Mikiko Sodeoka, Hideo Kigoshi
We have established an efficient synthetic methodology for the 13-oxyingenol natural derivative (13-oxyingenol-13-dodecanoate-20-hexanoate), featuring a ring-closing olefin metathesis reaction for the "direct" construction of a highly strained inside-outside framework and a Mislow-Evans-type [2,3]-sigmatropic rearrangement for the stereoselective introduction of the hydroxy group at C5. We also synthesized artificial analogs of 13-oxyingenol and ingenol by using our synthetic strategy. In vitro activation assays of protein kinase C (PKC) α and δ revealed that the dodecanoyl group at O13 on 13-oxyingenol analogs had a significant role in PKCδ activation...
November 22, 2016: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/27871063/dioscorea-esculenta-induced-increase-in-muscle-sex-steroid-hormones-is-associated-with-enhanced-insulin-sensitivity-in-a-type-2-diabetes-rat-model
#18
Koji Sato, Satoshi Fujita, Motoyuki Iemitsu
The effects of chronic Dioscorea esculenta administration and exercise training on muscle sex steroid hormone levels and insulin resistance in type 2 diabetes rats was assessed. Twenty-wk-old male Otsuka Long Evans Tokushima Fatty (OLETF) rats were assigned randomly to the control, D. esculenta treatment, D. esculenta with 5α-reductase inhibitor treatment, or the exercise training groups (running at 25 m/min for 1 h, 5 d/wk; n = 10 each group). Eight weeks of D. esculenta treatment or exercise training significantly attenuated the increase in plasma insulin and fasting glucose levels...
November 8, 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/27869138/the-helminth-product-es-62-modulates-dendritic-cell-responses-by-inducing-the-selective-autophagolysosomal-degradation-of-tlr-transducers-as-exemplified-by-pkc%C3%AE
#19
Russell J Eason, Kara S Bell, Fraser A Marshall, David T Rodgers, Miguel A Pineda, Christina N Steiger, Lamyaa Al-Riyami, William Harnett, Margaret M Harnett
We have previously shown that ES-62, a phosphorylcholine (PC)-containing glycoprotein secreted by the parasitic filarial nematode Acanthocheilonema viteae targets dendritic cell (DC) responses, specifically by suppressing TLR4 signalling to inhibit Th1/Th17-driven inflammation. We have now investigated the molecular mechanisms underpinning such immunomodulation and show here that ES-62-mediated downregulation of protein kinase C-δ (PKC-δ), a TLR4-associated signalling mediator required for full activation of LPS-driven pro-inflammatory responses, is associated with induction of a low level of autophagic flux, as evidenced by upregulation and trafficking of p62 and LC3 and their consequent autophagolysosomal degradation...
November 21, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27866837/high-density-lipoproteins-exert-pro-inflammatory-effects-on-macrophages-via-passive-cholesterol-depletion-and-pkc-nf-%C3%AE%C2%BAb-stat1-irf1-signaling
#20
Emiel P C van der Vorst, Kosta Theodorou, Yongzheng Wu, Marten A Hoeksema, Pieter Goossens, Christina A Bursill, Taghi Aliyev, Leonie F A Huitema, Sander W Tas, Ine M J Wolfs, Marijke J E Kuijpers, Marion J Gijbels, Casper G Schalkwijk, Debby P Y Koonen, Shahla Abdollahi-Roodsaz, Kimberly McDaniels, Chih-Chieh Wang, Michael Leitges, Toby Lawrence, Jogchum Plat, Miranda Van Eck, Kerry-Anne Rye, Lhousseine Touqui, Menno P J de Winther, Erik A L Biessen, Marjo M P C Donners
Membrane cholesterol modulates a variety of cell signaling pathways and functions. While cholesterol depletion by high-density lipoproteins (HDLs) has potent anti-inflammatory effects in various cell types, its effects on inflammatory responses in macrophages remain elusive. Here we show overt pro-inflammatory effects of HDL-mediated passive cholesterol depletion and lipid raft disruption in murine and human primary macrophages in vitro. These pro-inflammatory effects were confirmed in vivo in peritoneal macrophages from apoA-I transgenic mice, which have elevated HDL levels...
November 16, 2016: Cell Metabolism
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