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https://www.readbyqxmd.com/read/28719888/inhibition-of-single-routes-of-intracellular-signaling-is-not-sufficient-to-neutralize-the-biphasic-disturbance-of-a-retinal-endothelial-cell-barrier-induced-by-vegf-a165
#1
Heidrun L Deissler, Gerhard K Lang, Gabriele E Lang
BACKGROUND/AIMS: Hallmark of diabetic macular edema is the enhanced permeability of retinal endothelial cells (REC) induced by vascular endothelial growth factor (VEGF-A165), which acts through activating specific receptors. To improve the predictability of inhibitors' potentials to block harmful effects of VEGF-A165, we investigated if its signaling pathways triggered in REC are redundant. METHODS: Immortalized bovine REC monolayers were treated with inhibitors specific for various protein kinases in combination with VEGF-A165...
July 18, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28719725/effects-of-eupatilin-on-the-contractility-of-corpus-cavernosal-smooth-muscle-through-nitric-oxide-independent-pathways
#2
S H Choo, S W Lee, M R Chae, S J Kang, H H Sung, D H Han, J N Chun, J K Park, C Y Kim, H K Kim, I So
Eupatilin (5,7-dihydroxy-3,4,6-trimethoxyflavone) is one of the main compounds present in Artemisia species. Eupatilin has both antioxidative and anti-inflammatory properties and a relaxation effect on vascular contraction regardless of endothelial function. We evaluated the relaxant effects of eupatilin on the corpus cavernosum (CC) of rabbits and the underlying mechanisms of its activity in human corpus cavernosum smooth muscle (CCSM) cells. Isolated rabbit CC strips were mounted in an organ bath system. A conventional whole-cell patch clamp technique was used to measure activation of calcium-sensitive K(+) -channel currents in human CCSM cells...
July 18, 2017: Andrology
https://www.readbyqxmd.com/read/28719670/suppressive-effect-of-amp-activated-protein-kinase-on-the-epithelial-mesenchymal-transition-in-retinal-pigment-epithelial-cells
#3
Ryo Matoba, Yuki Morizane, Yusuke Shiode, Masayuki Hirano, Shinichiro Doi, Shinji Toshima, Ryoichi Araki, Mika Hosogi, Tomoko Yonezawa, Fumio Shiraga
The epithelial-mesenchymal transition (EMT) in retinal pigment epithelial (RPE) cells plays a central role in the development of proliferative vitreoretinopathy (PVR). The purpose of this study was to investigate the effect of AMP-activated protein kinase (AMPK), a key regulator of energy homeostasis, on the EMT in RPE cells. In this study, EMT-associated formation of cellular aggregates was induced by co-stimulation of cultured ARPE-19 cells with tumor necrosis factor (TNF)-α (10 ng/ml) and transforming growth factor (TGF)-β2 (5 ng/ml)...
2017: PloS One
https://www.readbyqxmd.com/read/28719152/a-first-in-human-phase-i-multicenter-open-label-dose-escalation-study-of-the-oral-raf-vegfr-2-inhibitor-raf265-in-locally-advanced-or-metastatic-melanoma-independent-from-braf-mutation-status
#4
Benjamin Izar, William Sharfman, F Stephen Hodi, Donald Lawrence, Keith T Flaherty, Ravi Amaravadi, Kevin B Kim, Igor Puzanov, Jeffrey Sosman, Reinhard Dummer, Simone M Goldinger, Lyhping Lam, Shefali Kakar, Zhongwen Tang, Oliver Krieter, David F McDermott, Michael B Atkins
To establish the maximum tolerated dose (MTD), dose-limiting toxicities (DLT), safety profile, and anti-tumor efficacy of RAF265. We conducted a multicenter, open-label, phase-I, dose-escalation trial of RAF265, an orally available RAF kinase/VEGFR-2 inhibitor, in patients with advanced or metastatic melanoma. Pharmacokinetic (PK) analysis, pharmacodynamics (PD) and tumor response assessment were conducted. We evaluated metabolic tumor response by 18[F]-fluorodeoxyglucose-positron-emission tomography (FDG-PET), tissue biomarkers using immunohistochemistry (IHC), and modulators of angiogenesis...
July 18, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28719054/evolutionary-cell-biology-of-proteins-from-protists-to-humans-and-plants
#5
REVIEW
Helmut Plattner
During evolution, the cell as a fine-tuned machine had to undergo permanent adjustments to match changes in its environment, while "closed for repair work" was not possible. Evolution from protists (protozoa and unicellular algae) to multicellular organisms may have occurred in basically two lineages, Unikonta and Bikonta, culminating in mammals and angiosperms (flowering plants), respectively. Unicellular models for unikont evolution are myxamoebae (Dictyostelium) and increasingly also choanoflagellates, whereas, for bikonts, ciliates are preferred models...
July 18, 2017: Journal of Eukaryotic Microbiology
https://www.readbyqxmd.com/read/28718842/secreted-protein-acidic-and-rich-in-cysteine-sparc-enhances-cell-proliferation-migration-and-epithelial-mesenchymal-transition-and-sparc-expression-is-associated-with-tumor-grade-in-head-and-neck-cancer
#6
Chih-Hau Chang, Meng-Chi Yen, Ssu-Hui Liao, Yu-Ling Hsu, Chung-Sheng Lai, Kao-Ping Chang, Ya-Ling Hsu
Secreted protein acidic and rich in cysteine (SPARC) is a secreted protein which is involved in various biological processes. SPARC expression is associated with tumor metastasis and poor prognosis in several types of cancer. However, the SPARC-induced signaling pathway was not fully understood in head and neck cancer. In this study, our results showed that SPARC treatment promoted cell proliferation and migration in head and neck cancer cell lines FaDu and Detroit 562. In addition, SPARC induced expression of epithelial mesenchymal transition (EMT) regulators, including Slug, Snail, and Twist in Detroit 562...
July 18, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28718798/co-expression-network-and-pathway-analyses-reveal-important-modules-of-mirnas-regulating-milk-yield-and-component-traits
#7
Duy N Do, Pier-Luc Dudemaine, Ran Li, Eveline M Ibeagha-Awemu
Co-expression network analyses provide insights into the molecular interactions underlying complex traits and diseases. In this study, co-expression network analysis was performed to detect expression patterns (modules or clusters) of microRNAs (miRNAs) during lactation, and to identify miRNA regulatory mechanisms for milk yield and component traits (fat, protein, somatic cell count (SCC), lactose, and milk urea nitrogen (MUN)) via miRNA target gene enrichment analysis. miRNA expression (713 miRNAs), and milk yield and components (Fat%, Protein%, lactose, SCC, MUN) data of nine cows at each of six different time points (day 30 (D30), D70, D130, D170, D230 and D290) of an entire lactation curve were used...
July 18, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28718701/occludin-regulates-glucose-uptake-and-atp-production-in-pericytes-by-influencing-amp-activated-protein-kinase-activity
#8
Victor Castro, Marta Skowronska, Jorge Lombardi, Jane He, Neil Seth, Martina Velichkovska, Michal Toborek
Energetic regulation at the blood-brain barrier is critical for maintaining its integrity, transport capabilities, and brain demands for glucose. However, the underlying mechanisms that regulate these processes are still poorly explored. We recently characterized the protein occludin as a NADH oxidase and demonstrated its influence on the expression and activation of the histone deacetylase SIRT-1. Because SIRT-1 works in concert with AMP-activated protein kinase (AMPK) (AMPK), we investigated the impact of occludin on this metabolic switch...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/28718511/genome-wide-identification-of-genes-involved-in-the-potato-response-to-drought-indicates-functional-evolutionary-conservation-with-arabidopsis-plants
#9
M Pieczynski, A Wyrzykowska, K Milanowska, D Boguszewska-Mankowska, B Zagdanska, W Karlowski, A Jarmolowski, Z Szweykowska-Kulinska
Potato is one of the four most important food crop plants worldwide and is strongly affected by drought. The following two pairs of potato cultivars, which are related in ancestry but show different drought tolerances, were chosen for comparative gene expression studies: Gwiazda/Oberon and Tajfun/Owacja. Comparative RNA-seq analyses of gene expression differences in the transcriptomes obtained from drought-tolerant versus drought-sensitive plants during water shortage conditions were performed. The twenty-three top-ranking genes were selected, 22 of which are described here as novel potato drought-responsive genes...
July 17, 2017: Plant Biotechnology Journal
https://www.readbyqxmd.com/read/28718374/cancer-associated-fibroblasts-secrete-fgf-1-to-promote-ovarian-proliferation-migration-and-invasion-through-the-activation-of-fgf-1-fgfr4-signaling
#10
Yuanzhen Sun, Xiaoli Fan, Qing Zhang, Xiaoyu Shi, Guangwei Xu, Cuimin Zou
Ovarian cancer is the most lethal gynecologic malignancy, due to its high propensity for metastasis. Cancer-associated fibroblasts, as the dominant component of tumor microenvironment, are crucial for tumor progression. However, the mechanisms underlying the regulation of ovarian cancer cells by cancer-associated fibroblasts remain little known. Here, we first isolated cancer-associated fibroblasts from patients' ovarian tissues and found that cancer-associated fibroblasts promoted SKOV3 cells' proliferation, migration, and invasion...
July 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28718286/functionalized-selenium-nanosystem-as-radiation-sensitizer-of-125i-seeds-for-precise-cancer-therapy
#11
Yahui Yang, Qiang Xie, Zhennan Zhao, Lizhen He, Leung Chan, Yingxiang Liu, Yongle Chen, Mingjun Bai, Tao Pan, Yanni Qu, Long Ling, Tianfeng Chen
Although radiotherapy has been extensively applied in cancer treatment, external beam radiation therapy is still difficult to avoid damage to adjacent normal tissues in the process of delivering a sufficient radiation dose to the tumor sites of patients. To overcome this limitation, chemoradiotherapy, as a combination of chemotherapy and radiotherapy of radioactive seed, has been proposed to decrease the damage for tumor surrounding tissues and enhance the radiosensitivity of solid tumors. In the study, we designed and synthesized folic acid-conjugated selenium nanoparticles (FA@SeNPs) as cancer-targeting agent, which could be synergistically enhanced by the radioactive 125I seeds to realize anticancer efficacy and inhibited colony formation ability...
July 18, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28717875/mast-like-protein-kinase-ireh1-from-arabidopsis-thaliana-co-localizes-with-the-centrosome-when-expressed-in-animal-cells
#12
Elena M Chudinova, Pavel A Karpov, Artem I Fokin, Alla I Yemets, Dmytro I Lytvyn, Elena S Nadezhdina, Yaroslav B Blume
The similarity of IREH1 (Incomplete Root Hair Elongation 1) and animal MAST kinases was confirmed; IREH1cDNA was cloned while expressing in cultured animal cells co-localized with the centrosome. In mammals and fruit flies, microtubule-associated serine/threonine-protein kinases (MAST) are strongly involved in the regulation of the microtubule system. Higher plants also possess protein kinases homologous to MASTs, but their function and interaction with the cytoskeleton remain unclear. Here, we confirmed the sequence and structural similarity of MAST-related putative protein kinase IREH1 (At3g17850) and known animal MAST kinases...
July 17, 2017: Planta
https://www.readbyqxmd.com/read/28717253/prostacyclin-reverses-platelet-stress-fibre-formation-causing-platelet-aggregate-instability
#13
M Z Yusuf, Z Raslan, L Atkinson, A Aburima, S G Thomas, K M Naseem, S D J Calaminus
Prostacyclin (PGI2) modulates platelet activation to regulate haemostasis. Evidence has emerged to suggest that thrombi are dynamic structures with distinct areas of differing platelet activation. It was hypothesised that PGI2 could reverse platelet spreading by actin cytoskeletal modulation, leading to reduced capability of platelet aggregates to withstand a high shear environment. Our data demonstrates that post-flow of PGI2 over activated and spread platelets on fibrinogen, identified a significant reduction in platelet surface area under high shear...
July 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28717149/transcriptome-analysis-of-rice-seedling-roots-in-response-to-potassium-deficiency
#14
Xiaoqin Zhang, Hua Jiang, Hua Wang, Jun Cui, Jiahui Wang, Jiang Hu, Longbiao Guo, Qian Qian, Dawei Xue
Rice is one of the most important food crops in the world, and its growth, development, yield, and grain quality are susceptible to a deficiency of the macronutrient potassium (K(+)). The molecular mechanism for K(+) deficiency tolerance remains poorly understood. In this study, K(+) deficient conditions were employed to investigate the resulting changes in the transcriptome of rice seedling roots. Using ribonucleic acid sequencing (RNA-Seq) and analysis, a total of 805 differentially expressed genes were obtained, of which 536 genes were upregulated and 269 were downregulated...
July 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28717010/phosphorylation-of-the-kainate-receptor-kar-auxiliary-subunit-neto2-at-serine-409-regulates-synaptic-targeting-of-the-kar-subunit-gluk1
#15
Richa Madan Lomash, Nengyin Sheng, Yan Li, Roger A Nicoll, Katherine W Roche
Synaptic strength at excitatory synapses is determined by the presence of glutamate receptors (i.e. AMPA, NMDA and kainate receptors) at the synapse. Synaptic strength is modulated by multiple factors including assembly of different receptor subunits, interaction with auxiliary subunits and post translational modifications of either the receptors or their auxiliary subunits. Using mass spectrometry, we find that the intracellular region of neuropilin and tolloid-like proteins (Neto)1 and Neto2, the auxiliary subunits of KARs are phosphorylated by multiple kinases in vitro...
July 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28716990/proof-of-principle-for-a-novel-class-of-antihypertensives-that-target-the-oxidative-activation-of-protein-kinase-g-i%C3%AE
#16
Joseph R Burgoyne, Oleksandra Prysyazhna, Daniel A Richards, Philip Eaton
Arterial hypertension continues to be a major health burden. Development of new antihypertensive drugs that engage vasodilatory mechanisms not harnessed by available therapies offer therapeutic potential. Oxidants induce an interprotein disulfide in protein kinase G Iα (PKG Iα) at C42, which is associated with its targeting and activation, resulting in vasodilation and blood pressure lowering. Consequently, we developed an assay and screened for electrophilic drugs that activate PKG Iα by selectively targeting C42, as such compounds have potential as novel antihypertensives with a mechanism of action that differs from current therapies...
July 17, 2017: Hypertension
https://www.readbyqxmd.com/read/28716986/development-of-protein-kinase-g-i%C3%AE-dimerizing-antihypertensive-drugs-are-we-standing-at-the-shore-of-the-rubicon
#17
EDITORIAL
Paula K Bautista-Niño, Anton J M Roks, A H Jan Danser
No abstract text is available yet for this article.
July 17, 2017: Hypertension
https://www.readbyqxmd.com/read/28716951/a-calcium-diacylglycerol-stimulated-protein-kinase-c-c-elegans-pkc-2-links-thermal-signals-to-learned-behavior-by-acting-in-a-sensory-neuron-and-intestinal-cells
#18
Marianne Land, Charles S Rubin
Ca(2+) and diacylglycerol (DAG) activated protein kinase C (cPKC) promotes learning and behavioral plasticity. However, knowledge of in vivo regulation and exact functions of cPKCs that affect behavior is limited. We show that PKC-2, a C. elegans cPKC, is essential for a complex behavior, thermotaxis. C. elegans memorizes a nutrient-associated cultivation temperature (Tc) and migrates along Tc within a 17-25°C gradient. pkc-2 gene disruption abrogated thermotaxis; a PKC-2 transgene, driven by endogenous pkc-2 promoters, restored thermotaxis behavior in pkc-2(-/-) animals...
July 17, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28716922/local-destabilization-rigid-body-and-fuzzy-docking-facilitate-the-phosphorylation-of-the-transcription-factor-ets-1-by-the-mitogen-activated-protein-kinase-erk2
#19
Andrea Piserchio, Mangalika Warthaka, Tamer S Kaoud, Kari Callaway, Kevin N Dalby, Ranajeet Ghose
Mitogen-activated protein (MAP) kinase substrates are believed to require consensus docking motifs (D-site, F-site) to engage and facilitate efficient site-specific phosphorylation at specific serine/threonine-proline sequences by their cognate kinases. In contrast to other MAP kinase substrates, the transcription factor Ets-1 has no canonical docking motifs, yet it is efficiently phosphorylated by the MAP kinase ERK2 at a consensus threonine site (T38). Using NMR methodology, we demonstrate that this phosphorylation is enabled by a unique bipartite mode of ERK2 engagement by Ets-1 and involves two suboptimal noncanonical docking interactions instead of a single canonical docking motif...
July 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28716882/protein-kinase-d-at-the-golgi-controls-nlrp3-inflammasome-activation
#20
Zhirong Zhang, Gergö Meszaros, Wan-Ting He, Yanfang Xu, Helena de Fatima Magliarelli, Laurent Mailly, Michael Mihlan, Yansheng Liu, Marta Puig Gámez, Alexander Goginashvili, Adrien Pasquier, Olga Bielska, Bénédicte Neven, Pierre Quartier, Rudolf Aebersold, Thomas F Baumert, Philippe Georgel, Jiahuai Han, Romeo Ricci
The inflammasomes are multiprotein complexes sensing tissue damage and infectious agents to initiate innate immune responses. Different inflammasomes containing distinct sensor molecules exist. The NLRP3 inflammasome is unique as it detects a variety of danger signals. It has been reported that NLRP3 is recruited to mitochondria-associated endoplasmic reticulum membranes (MAMs) and is activated by MAM-derived effectors. Here, we show that in response to inflammasome activators, MAMs localize adjacent to Golgi membranes...
July 17, 2017: Journal of Experimental Medicine
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