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https://www.readbyqxmd.com/read/28222515/meta-analysis-of-parkinson-s-disease-and-alzheimer-s-disease-revealed-commonly-impaired-pathways-and-dysregulation-of-nrf2-dependent-genes
#1
Qian Wang, Wen-Xing Li, Shao-Xing Dai, Yi-Cheng Guo, Fei-Fei Han, Jun-Juan Zheng, Gong-Hua Li, Jing-Fei Huang
Many lines of evidence suggest that Parkinson's disease (PD) and Alzheimer's disease (AD) have common characteristics, such as mitochondrial dysfunction and oxidative stress. As the underlying molecular mechanisms are unclear, we perform a meta-analysis with 9 microarray datasets of PD studies and 7 of AD studies to explore it. Functional enrichment analysis revealed that PD and AD both showed dysfunction in the synaptic vesicle cycle, GABAergic synapses, phagosomes, oxidative phosphorylation, and TCA cycle pathways, and AD had more enriched genes...
February 7, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28222424/1%C3%AE-25-oh-2d3-sensitive-cytosolic-ph-regulation-and-glycolytic-flux-in-human-endometrial-ishikawa-cells
#2
Ni Zeng, Yuetao Zhou, Shaqiu Zhang, Yogesh Singh, Bing Shi, Madhuri S Salker, Florian Lang
BACKGROUND/AIMS: Tumor cell proliferation is modified by 1,25-Dihydroxy-Vitamin D3 (1,25(OH)2D3), a steroid hormone predominantly known for its role in calcium and phosphorus metabolism. Key properties of tumor cells include enhanced glycolytic flux with excessive consumption of glucose and formation of lactate. As glycolysis is highly sensitive to cytosolic pH, maintenance of glycolysis requires export of H+ ions and lactate, which is in part accomplished by Na+/H+ exchangers, such as NHE1 and monocarboxylate transporters, such as MCT4...
February 8, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28222421/luteolin-enhances-sarcoplasmic-reticulum-ca2-atpase-activity-through-p38-mapk-signaling-thus-improving-rat-cardiac-function-after-ischemia-reperfusion
#3
Shasha Zhu, Tongda Xu, Yuanyuan Luo, Yingying Zhang, Haochen Xuan, Yanfeng Ma, Defeng Pan, Dongye Li, Hong Zhu
BACKGROUND/AIMS: A major challenge for current therapeutic strategies against ischemia/reperfusion (I/R) is the lack of effective drugs. Considering luteolin enhances the activity of sarcoplasmic reticulum Ca2+-ATPase (SERCA2a) to improve the systolic/diastolic function of rat hearts and cardiomyocytes during the I/R process, we studied the regulatory function of the p38 MAPK pathway in this protective mechanism. METHODS: Isolated cardiomyocytes and perfused hearts were separately divided into five groups and used to investigate I/R...
February 21, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28222177/phospholipid-binding-to-the-fak-catalytic-domain-impacts-function
#4
Jessica E Hall, Michael D Schaller
Focal adhesion kinase is an essential nonreceptor tyrosine kinase that plays an important role in development, in homeostasis and in the progression of human disease. Multiple stimuli activate FAK, which requires a change in structure from an autoinhibited to activated conformation. In the autoinhibited conformation the FERM domain associates with the catalytic domain of FAK and PI(4,5)P2 binding to the FERM domain plays a role in the release of autoinhibition, activating the enzyme. An in silico model of FAK/PI(4,5)P2 interaction suggests that residues on the catalytic domain interact with PI(4,5)P2, in addition to the known FERM domain PI(4,5)P2 binding site...
2017: PloS One
https://www.readbyqxmd.com/read/28222148/microrna-200a-silencing-protects-neural-stem-cells-against-cerebral-ischemia-reperfusion-injury
#5
Ji Ma, Shaofeng Shui, Xinwei Han, Dong Guo, Tengfei Li, Lei Yan
Neural stem cells (NSCs) play major roles in neurological recovery after cerebral infarction (CI). This study was trying to investigate whether miR-200a, a vital regulator in cell proliferation, migration and apoptosis, also has a role in oxygen-glucose deprivation/reperfusion (OGD/R) injured NSCs. In this study, primary NSCs were subjected to OGD/R conditions to mimic an in vitro CI model. Before OGD/R induction, NSCs were transfected with vector or shRNA against miR-200a to overexpress or suppress miR-200a expression...
2017: PloS One
https://www.readbyqxmd.com/read/28222108/oxidative-stress-mediated-nf%C3%AE%C2%BAb-phosphorylation-upregulates-p62-sqstm1-and-promotes-retinal-pigmented-epithelial-cell-survival-through-increased-autophagy
#6
Chunjuan Song, Sayak K Mitter, Xiaoping Qi, Eleni Beli, Haripriya V Rao, Jindong Ding, Colin S Ip, Hongmei Gu, Debra Akin, William A Dunn, Catherine Bowes Rickman, Alfred S Lewin, Maria B Grant, Michael E Boulton
p62 is a scaffolding adaptor implicated in the clearance of protein aggregates by autophagy. Reactive oxygen species (ROS) can either stimulate or inhibit NFκB-mediated gene expression influencing cellular fate. We studied the effect of hydrogen peroxide (H2O2)-mediated oxidative stress and NFκB signaling on p62 expression in the retinal pigment epithelium (RPE) and investigated its role in regulation of autophagy and RPE survival against oxidative damage. Cultured human RPE cell line ARPE-19 and primary human adult and fetal RPE cells were exposed to H2O2-induced oxidative stress...
2017: PloS One
https://www.readbyqxmd.com/read/28222070/inhibition-of-polypyrimidine-tract-binding-protein-3-induces-apoptosis-and-cell-cycle-arrest-and-enhances-the-cytotoxicity-of-5-fluorouracil-in-gastric-cancer-cells
#7
Xin Liang, Haiyang Shi, Liyan Yang, Cen Qiu, Shengchao Lin, Yingxue Qi, Jiyu Li, Aiguang Zhao, Jianwen Liu
BACKGROUND: Human polypyrimidine tract binding protein 3 (PTBP3) was first discovered in 1999 and has been well characterised as a differentiation regulator. However, its role in human cancer has rarely been reported. Our previous study revealed increased PTBP3 protein level in gastric cancer tissues. Downregulation of PTBP3 suppressed the proliferation and differentiation of gastric cancer cells in vivo. METHODS: PTBP3 mRNA levels in human gastric cancer and adjuvant non-tumour tissues were detected...
February 21, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28222042/compound-effects-of-aging-and-experimental-fsgs-on-glomerular-epithelial-cells
#8
Remington R S Schneider, Diana G Eng, J Nathan Kutz, Mariya T Sweetwyne, Jeffrey W Pippin, Stuart J Shankland
Advanced age portends a poorer prognosis in FSGS. To understand the impact of age on glomerular podocytes and parietal epithelial cells (PECs), experimental FSGS was induced in 3m-old mice (20-year old human age) and 27m-old mice (78-year old human age) by abruptly depleting podocytes with a cytopathic anti-podocyte antibody. Despite similar binding of the disease-inducing antibody, podocyte density was lower in aged FSGS mice compared to young FSGS mice. Activated PEC density was higher in aged versus young FSGS mice, as was the percentage of total activated PECs...
February 17, 2017: Aging
https://www.readbyqxmd.com/read/28221700/multikinase-inhibitors-sorafenib-and-sunitinib-as-radiosensitizers-in-head-and-neck-cancer-cell-lines
#9
Annette Affolter, Gerson Samosny, Anne-Sophie Heimes, Johanna Schneider, Wilko Weichert, Albrecht Stenzinger, Katharina Sommer, Alexandra Jensen, Arnulf Mayer, Walburgis Brenner, Wolf J Mann, Jürgen Brieger
BACKGROUND: Radioresistance is a common feature of head and neck squamous cell carcinoma (HNSCC). We previously showed that the irradiation- activated vascular endothelial growth factor (VEGF)-extracellular signal-regulated kinase (ERK)-axis is fundamental for the survival of resistant tumors. In this study, we examined if treatment with potent multikinase (MK) inhibitors, sorafenib and sunitinib, could radiosensitize tumor cells. METHODS: Cultured HNSCC cell lines were treated with inhibitors and subsequently irradiated...
February 21, 2017: Head & Neck
https://www.readbyqxmd.com/read/28220896/mitochondrial-dysregulation-secondary-to-endoplasmic-reticulum-stress-in-autosomal-dominant-tubulointerstitial-kidney-disease-umod-adtkd-umod
#10
Elisabeth Kemter, Thomas Fröhlich, Georg J Arnold, Eckhard Wolf, Rüdiger Wanke
'Autosomal dominant tubulointerstitial kidney disease - UMOD' (ADTKD-UMOD) is caused by impaired maturation and secretion of mutant uromodulin (UMOD) in thick ascending limb of Henle loop (TAL) cells, resulting in endoplasmic reticulum (ER) stress and unfolded protein response (UPR). To gain insight into pathophysiology, we analysed proteome profiles of TAL-enriched outer renal medulla samples from ADTKD-UMOD and control mice by quantitative LC-MS/MS. In total, 212 differentially abundant proteins were identified...
February 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28220887/mass-spectrometric-analysis-of-trpm6-and-trpm7-phosphorylation-reveals-regulatory-mechanisms-of-the-channel-kinases
#11
Na Cai, Zhiyong Bai, Vikas Nanda, Loren W Runnels
TRPM7 and TRPM6 were the first identified bifunctional channels to contain their own kinase domains, but how these channel-kinases are regulated is poorly understood. Previous studies identified numerous phosphorylation sites on TRPM7, but very little is known about TRPM6 phosphorylation or sites on TRPM7 transphosphorylated by TRPM6. Our mass spectrometric analysis of homomeric and heteromeric TRPM7 and TRPM6 channels identified phosphorylation sites on both proteins, as well as several prominent sites on TRPM7 that are commonly modified through autophosphorylation and transphosphorylation by TRPM6...
February 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28220885/cancer-cell-mitochondria-targeting-by-pancratistatin-analogs-is-dependent-on-functional-complex-ii-and-iii
#12
Dennis Ma, Christopher Pignanelli, Daniel Tarade, Tyler Gilbert, Megan Noel, Fadi Mansour, Scott Adams, Alexander Dowhayko, Kyle Stokes, Sergey Vshyvenko, Tomas Hudlicky, James McNulty, Siyaram Pandey
Enhanced mitochondrial stability and decreased dependence on oxidative phosphorylation confer an acquired resistance to apoptosis in cancer cells, but may present opportunities for therapeutic intervention. The compound pancratistatin (PST) has been shown to selectively induce apoptosis in cancer cells. However, its low availability in nature has hindered its clinical advancement. We synthesized PST analogs and a medium-throughput screen was completed. Analogs SVTH-7, -6, and -5 demonstrated potent anti-cancer activity greater than PST and several standard chemotherapeutics...
February 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28220880/parenteral-administration-of-factor-xa-iia-inhibitors-limits-experimental-aortic-aneurysm-and-atherosclerosis
#13
Corey S Moran, Sai-Wang Seto, Smriti M Krishna, Surabhi Sharma, Roby J Jose, Erik Biros, Yutang Wang, Susan K Morton, Jonathan Golledge
Intraluminal thrombus is a consistent feature of human abdominal aortic aneurysm (AAA). Coagulation factor Xa (FXa) catalyses FII to thrombin (FIIa). We examined the effect of FXa/FIIa inhibition on experimental aortic aneurysm in apolipoprotein E-deficient (ApoE(-/-)) mice infused with angiotensin II (AngII). The concentration of FXa within the supra-renal aorta (SRA) correlated positively with SRA diameter. Parenteral administration of enoxaparin (FXa/IIa inhibitor) and fondaparinux (FXa inhibitor) over 14 days reduced to severity of aortic aneurysm and atherosclerosis in AngII-infused ApoE(-/-) mice...
February 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28220794/flucrypyrim-a-novel-uterine-relaxant-has-antinociceptive-and-anti-inflammatory-effects-in-vivo
#14
Zhongtang Li, Limei Wang, Yue Cong, Lin Guo, Xiaohui Lin, Zuyin Yu, Xingan Wu, Junxing Dong, Rifang Yang, Yuwen Cong
Consequences of primary dsysmenorrhea (PD) can be severe. Increased prostaglandin production leads to uterine contraction and insufficient blood flow to the endometrium causing ischemia and pain symptoms. Protein tyrosine kinase/phosphatase activities contribute to the modulation of uterine contraction. In our previous study, we found the synthetic β-methoxyacrylates compound Fluacrypyrim (FAPM), significantly increased protein tyrosine phosphatases (PTPs) activity, resulting in dephosphorylation of tyrosine kinases...
February 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28220785/c-edge-loops-of-arrestin-function-as-a-membrane-anchor
#15
Ciara C M Lally, Brian Bauer, Jana Selent, Martha E Sommer
G-protein-coupled receptors are membrane proteins that are regulated by a small family of arrestin proteins. During formation of the arrestin-receptor complex, arrestin first interacts with the phosphorylated receptor C terminus in a pre-complex, which activates arrestin for tight receptor binding. Currently, little is known about the structure of the pre-complex and its transition to a high-affinity complex. Here we present molecular dynamics simulations and site-directed fluorescence experiments on arrestin-1 interactions with rhodopsin, showing that loops within the C-edge of arrestin function as a membrane anchor...
February 21, 2017: Nature Communications
https://www.readbyqxmd.com/read/28220552/activation-of-the-mtor-dependent-signaling-pathway-underlies-ketamine-induced-uropathy
#16
Chih-Chieh Lin, An-Hang Yang, Alex Tong-Long Lin
AIMS: To investigate the pathogenic role of activation of the mammalian target of the rapamycin (mTOR) in the ketamine induced microvascular injury. METHODS: Twenty-three patients with ketamine-induced cystitis (KC) and 16 control volunteers were recruited. Bladder tissues were obtained from both groups by cystoscopic biopsies. Phospho-S6 ribosomal protein (p-S6RP), an end product of the mTOR pathway, was stained in the urinary bladder from both groups. Endothelial cells of the urinary bladder (HBdMECs) were examined to investigate the in vitro activation of the mTOR pathway and the co-expression of the endothelial marker (cluster of differentiation 31 [CD31]) and the mesenchymal marker (fibroblast-specific protein 1 [FSP-1])...
February 21, 2017: Neurourology and Urodynamics
https://www.readbyqxmd.com/read/28220438/methods-to-quantify-pamp-triggered-oxidative-burst-map-kinase-phosphorylation-gene-expression-and-lignification-in-brassicas
#17
Simon R Lloyd, Christopher J Ridout, Henk-Jan Schoonbeek
Quantitative disease resistance (QDR) based on PAMP-triggered immunity (PTI) could be durable and effective against many pathogens (broad spectrum). Development of methods to evaluate PTI responses in crops could therefore accelerate breeding for durable QDR. Most PTI-studies involved model plants such as Arabidopsis and Nicotiana benthamiana or cell cultures, and cannot be directly applied to diverse germplasm of crop plants.We developed methods to measure PTI in Brassica crop species (Lloyd et al., Mol Plant Microbe Interact 27:286-295, 2014) which we have elaborated and expanded here to enable their use for screening and evaluating germplasm for potential QDR in breeding programs...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28220425/chitin-and-stress-induced-protein-kinase-activation
#18
Chandra Kenchappa, Raquel Azevedo da Silva, Simon Bressendorff, Sabrina Stanimirovic, Jakob Olsen, Morten Petersen, John Mundy
The assays described here are pertinent to protein kinase studies in any plant. They include an immunoblot phosphorylation/activation assay and an in-gel activity assay for MAP kinases (MPKs) using the general protein kinase substrate myelin basic protein. They also include a novel in-gel peptide substrate assay for Snf1-related kinase family 2 members (SnRK2s). This kinase family-specific assay overcomes some limitations of in-gel assays and permits the identification of different types of kinase activities in total protein extracts...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28220424/cdpk-activation-in-prr-signaling
#19
Heike Seybold, Marie Boudsocq, Tina Romeis
Calcium-dependent protein kinases undergo a rapid biochemical activation in response to an intracellular Ca increase induced by the PRR-dependent perception of a pathogen-related stimulus. Based on SDS gel resolution, the in-gel kinase assay allows the analysis of multiple in vivo protein samples in parallel, combining the advantage of protein separation according to molecular mass with the activity read-out of a protein kinase assay. It thus enables to follow the transient CDPK activation and inactivation in response to in vivo elicitation with a time-wise resolution...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28220422/mapk-assays-in-arabidopsis-mamp-prr-signal-transduction
#20
Hoo Sun Chung, Jen Sheen
Activation of MAPK (Mitogen-Activated Protein Kinase) cascades after MAMP (Microbe-Associated Molecular Pattern) perception through PRR (Pattern Recognition Receptor) is one of the first conserved responses when plants encounter microbial organisms. Phosphorylation of various cellular factors in the MAMP-PRR pathway by MAPK cascades is critical for broad-spectrum plant innate immunity. Measurement of MAPK activation and identification of MAPK phosphorylation targets in the MAMP-PRR signal transduction pathway are essential to understand how plants reprogram their cellular processes to cope with unfavorable microbial attack...
2017: Methods in Molecular Biology
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