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Protein kinase C

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https://www.readbyqxmd.com/read/28551817/discovery-of-novel-inhibitors-for-leishmania-nucleoside-diphosphatase-kinase-ndk-based-on-its-structural-and-functional-characterization
#1
Arjun K Mishra, Nidhi Singh, Pragati Agnihotri, Shikha Mishra, Saurabh P Singh, Bala K Kolli, Kwang Poo Chang, Amogh A Sahasrabuddhe, M I Siddiqi, J Venkatesh Pratap
Nucleoside diphosphate kinases (NDKs) are ubiquitous enzymes that catalyze the transfer of the γ-phosphate moiety from an NTP donor to an NDP acceptor, crucial for maintaining the cellular level of nucleoside triphosphates (NTPs). The inability of trypanosomatids to synthesize purines de novo and their dependence on the salvage pathway makes NDK an attractive target to develop drugs for the diseases they cause. Here we report the discovery of novel inhibitors for Leishmania NDK based on the structural and functional characterization of purified recombinant NDK from Leishmania amazonensis...
May 27, 2017: Journal of Computer-aided Molecular Design
https://www.readbyqxmd.com/read/28551638/modulation-of-melanotransferrin-and-transferrin-receptor-1-tfrc-and-cd44-based-signaling-for-tfrc-up-regulation-in-human-melanoma-cells
#2
Friedemann Laube, Dagobert Glanz
BACKGROUND: The human melanoma cell line IGR-1 was used for the detection and regulation of both melanotransferrin (MTf) and transferrin receptor 1 (TFRC, CD71). While the function in iron transport of the TFRC is well documented the functional importance of MTf is not yet fully understood. Due to the up-regulation of TFRC by hyaluronan (HA) some components and aspects of CD44 signaling were investigated. MATERIALS AND METHODS: The cell-surface proteins MTf, TFRC and ERBB2 receptor tyrosine kinase 2 (ERBB2) were detected by immunoluminescent technique using different polyclonal and monoclonal antibodies...
June 2017: Anticancer Research
https://www.readbyqxmd.com/read/28551635/enhanced-susceptibility-to-5-fluorouracil-in-human-colon-cancer-cells-by-silencing-of-grp78
#3
Seungpil Yun, Yong-Seok Han, Jun Hee Lee, Sangmin Kim, Sang Hun Lee
BACKGROUND: Glucose-regulated protein (GRP78), also known as immunoglobulin heavy chain binding protein and as heat shock 70 kDa protein 5, is present in the endoplasmic reticulum (ER) membrane. GRP78 is generally expressed at low concentrations, but is increased by physiological stress. GRP78 is thought to protect against tissue or organ damage under pathological conditions, such as neurotoxic stress, myocardial infarction, or arteriosclerosis. In addition, in tumors, GRP78 expression is much higher than in normal tissues...
June 2017: Anticancer Research
https://www.readbyqxmd.com/read/28551494/isoimperatorin-attenuates-airway-inflammation-and-mucus-hypersecretion-in-an-ovalbumin-induced-murine-model-of-asthma
#4
Charith U B Wijerathne, Chang-Seob Seo, Ji-Won Song, Hee-Seon Park, Og-Sung Moon, Young-Suk Won, Hyo-Jung Kwon, Hwa-Young Son
Isoimperatorin (IMP), an active natural furocoumarin, has numerous pharmacologic effects, including anti-inflammatory, analgesic, antispasmodic, and anticancer activities. This study aimed to evaluate the preventive activity of IMP in an ovalbumin (OVA)-induced murine model of asthma and to investigate its possible molecular mechanisms. Female BALB/c mice were sensitized on days 0 and 14 via intraperitoneal injection of 20μg OVA. On days 21-23 after the initial sensitization, the mice received an airway challenge with OVA (1% w/v in PBS) for 1h; meanwhile, IMP (10 or 30mg/kg once daily) was administered by gavage on days 18-23...
May 25, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28551334/structure-and-dimerization-of-ireb-a-negative-regulator-of-cephalosporin-resistance-in-enterococcus-faecalis
#5
Cherisse L Hall, Betsy L Lytle, Davin Jensen, Jessica S Hoff, Francis C Peterson, Brian F Volkman, Christopher J Kristich
Enterococcus faecalis, a leading cause of hospital-acquired infections, exhibits intrinsic resistance to most cephalosporins, which are antibiotics in the beta-lactam family that target cell-wall biosynthesis. A comprehensive understanding of the underlying genetic and biochemical mechanisms of cephalosporin resistance in E. faecalis is lacking. We previously determined that a transmembrane serine-threonine kinase (IreK) and its cognate phosphatase (IreP) reciprocally regulate cephalosporin resistance in E...
May 24, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28551077/lipopolysaccharide-detection-across-the-kingdoms-of-life
#6
REVIEW
Jonathan C Kagan
Studies in recent years have uncovered a diverse set of eukaryotic receptors that recognize lipopolysaccharide (LPS), the major outer-membrane component of Gram-negative bacteria. Indeed, Toll-like receptors, G-protein-coupled receptors, integrins, receptor-like kinases, and caspases have emerged as important LPS-interacting proteins. In this review, the mammalian receptors that detect LPS are described. I highlight how no host protein is involved in all LPS responses, but a single lipid (phosphatidylinositol-4,5-bisphosphate) regulates many LPS responses, including endocytosis, phagocytosis, inflammation, and pyroptosis...
May 24, 2017: Trends in Immunology
https://www.readbyqxmd.com/read/28550731/xanthotoxin-suppresses-lps-induced-expression-of-inos-cox-2-tnf-%C3%AE-and-il-6-via-ap-1-nf-%C3%AE%C2%BAb-and-jak-stat-inactivation-in-raw-264-7-macrophages
#7
Seung-Bin Lee, Woo Seok Lee, Ji-Sun Shin, Dae Sik Jang, Kyung Tae Lee
Although xanthotoxin has been reported to possess skin-protective and anti-oxidative properties, its anti-inflammatory capacity has not been studied to date. Therefore, we investigated this role as well as the molecular mechanisms of xanthotoxin in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages. Xanthotoxin inhibited production of nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor (TNF-α), and interleukin-6 (IL-6) by the LPS-induced macrophages in a concentration-dependent manner. It also suppressed the LPS-induced inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression at the protein levels and iNOS, COX-2, TNF-α, and IL-6 at the mRNA levels...
May 24, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28550175/chronic-hypoxia-attenuates-the-vasodilator-efficacy-of-protein-kinase-g-in-fetal-and-adult-ovine-cerebral-arteries
#8
Richard B Thorpe, Margaret C Hubbell, Jinjutha Silpanisong, James M Williams, William J Pearce
Long-term hypoxia (LTH) attenuates nitric oxide (NO) induced vasorelaxation in ovine middle cerebral arteries. Because cGMP-dependent protein kinase (PKG) is an important mediator of NO signaling in vascular smooth muscle, we tested the hypothesis that LTH diminishes the ability of PKG to interact with target proteins and cause vasorelaxation. Prominent among proteins that regulate vascular tone is the large conductance calcium-sensitive potassium (BK) channel, which is a substrate for PKG and is responsive to phosphorylation on multiple serine/threonine residues...
May 26, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28550173/experimental-cardiac-radiation-exposure-induces-ventricular-diastolic-dysfunction-with-preserved-ejection-fraction
#9
Hirofumi Saiki, Gilles Moulay, Adam J Guenzel, Weibin Liu, Teresa Decklever, Kelly Classic, Linh Pham, Horng H Chen, John C Burnett, Stephen J Russell, Margaret M Redfield
BACKGROUND: Breast cancer radiotherapy increases the risk of heart failure (HF) with preserved ejection fraction (HFpEF). Cardiomyocytes are highly radio-resistant but radiation specifically affects coronary microvascular endothelial cells with subsequent microvascular inflammation and rarefaction. The effects of radiation on left ventricular (LV) diastolic function are poorly characterized. We hypothesized that cardiac radiation exposure may result in diastolic dysfunction without reduced EF...
May 26, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28550141/role-of-dynamin-src-and-ras-in-the-protein-kinase-c-mediated-activation-of-erk-by-gonadotropin-releasing-hormone
#10
Outhiriaradjou Benard, Zvi Naor, Rony Seger
No abstract text is available yet for this article.
May 26, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28550134/gq-protein-induced-apoptosis-is-mediated-by-akt-kinase-inhibition-that-leads-to-protein-kinase-c-induced-c-jun-n-terminal-kinase-activation
#11
Ido Ben-Ami, Zhong Yao, Zvi Naor, Rony Seger
No abstract text is available yet for this article.
May 26, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28550045/pacsin2-accelerates-nephrin-trafficking-and-is-up-regulated-in-diabetic-kidney-disease
#12
Vincent Dumont, Tuomas A Tolvanen, Sara Kuusela, Hong Wang, Tuula A Nyman, Sonja Lindfors, Jukka Tienari, Harry Nisen, Shiro Suetsugu, Markus Plomann, Hiroshi Kawachi, Sanna Lehtonen
Nephrin is a core component of podocyte (glomerular epithelial cell) slit diaphragm and is required for kidney ultrafiltration. Down-regulation or mislocalization of nephrin has been observed in diabetic kidney disease (DKD), characterized by albuminuria. Here, we investigate the role of protein kinase C and casein kinase 2 substrate in neurons 2 (PACSIN2), a regulator of endocytosis and recycling, in the trafficking of nephrin and development of DKD. We observe that PACSIN2 is up-regulated and nephrin mislocalized in podocytes of obese Zucker Diabetic Fatty (ZDF) rats that have altered renal function...
May 26, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28549941/dietary-zinc-deficiency-reduced-growth-performance-intestinal-immune-and-physical-barrier-functions-related-to-nf-%C3%AE%C2%BAb-tor-nrf2-jnk-and-mlck-signaling-pathway-of-young-grass-carp-ctenopharyngodon-idella
#13
Zheng-Xing Song, Wei-Dan Jiang, Yang Liu, Pei Wu, Jun Jiang, Xiao-Qiu Zhou, Sheng-Yao Kuang, Ling Tang, Wu-Neng Tang, Yong-An Zhang, Lin Feng
Our study investigated the effects of dietary zinc (Zn) deficiency on growth performance, intestinal immune and physical barrier functions of young grass carp (Ctenopharyngodon idella). A total of 630 grass carp (244.14 ± 0.40 g) were fed graded levels of zinc lactate (10.71, 30.21, 49.84, 72.31, 92.56, 110.78 mg Zn/kg diet) and one zinc sulfate group (56.9 mg Zn/kg diet) for 60 days. At the end of the feeding trial, fish were challenged with Aeromonas hydrophila for 14 days. These results indicated that compared with optimal dietary Zn level, dietary Zn deficiency (10...
May 23, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28549772/codon-optimized-rpgr-improves-stability-and-efficacy-of-aav8-gene-therapy-in-two-mouse-models-of-x-linked-retinitis-pigmentosa
#14
M Dominik Fischer, Michelle E McClements, Cristina Martinez-Fernandez de la Camara, Julia-Sophia Bellingrath, Daniyar Dauletbekov, Simon C Ramsden, Doron G Hickey, Alun R Barnard, Robert E MacLaren
X-linked retinitis pigmentosa (XLRP) is generally a severe form of retinitis pigmentosa, a neurodegenerative, blinding disorder of the retina. 70% of XLRP cases are due to mutations in the retina-specific isoform of the gene encoding retinitis pigmentosa GTPase regulator (RPGR(ORF15)). Despite successful RPGR(ORF15) gene replacement with adeno-associated viral (AAV) vectors being established in a number of animal models of XLRP, progression to human trials has not yet been possible. The inherent sequence instability in the purine-rich region of RPGR(ORF15) (which contains highly repetitive nucleotide sequences) leads to unpredictable recombination errors during viral vector cloning...
May 24, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28549558/the-kv1-3-channel-blocker-vm24-enhances-muscle-glucose-transporter-4-mobilization-but-does-not-reduce-body-weight-gain-in-diet-induced-obese-male-rats
#15
Lorraine Jaimes-Hoy, Georgina B Gurrola, Miguel Cisneros, Patricia Joseph-Bravo, Lourival D Possani, Jean-Louis Charli
AIMS: Voltage-gated potassium channels 1.3 (Kv1.3) can be targeted to reduce diet-induced obesity and insulin resistance in mice. Since species-specific differences in Kv1.3 expression and pharmacology have been observed, we tested the effect of Vm24, a high-affinity specific blocker of Kv1.3 channels from Vaejovis mexicanus smithi, on body weight (BW), glucose tolerance and insulin resistance in diet-induced obese rats. MATERIALS AND METHODS: Young adult male Wistar rats were switched to a high-fat/high-fructose (HFF) diet...
May 23, 2017: Life Sciences
https://www.readbyqxmd.com/read/28549343/hmgb1-mediated-autophagy-attenuates-gemcitabine-induced-apoptosis-in-bladder-cancer-cells-involving-jnk-and-erk-activation
#16
Hubin Yin, Xiaoyu Yang, Wen Gu, Yan Liu, Xinyuan Li, Xiaolong Huang, Xin Zhu, Yong Tao, Xin Gou, Weiyang He
High-mobility group box 1 (HMGB1) has been found to mediate autophagy during chemotherapy in several cancers. However, whether HMGB1plays a role in autophagy and chemoresistance in bladder cancer is elusive. In this report, HMGB1 expression was found to be increased in 30 primary bladder cancer tissue specimens compared to their matched adjacent non-tumor tissues. While gemcitabine induced apoptotic cell death, it also induced HMGB1 expression and autophagy in bladder cancer T24 and BIU-87 cells. Suppressing HMGB1 expression with siRNA strongly potentiated gemcitabine-induced apoptosis...
May 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28549111/diabetic-db-db-mice-do-not-develop-heart-failure-upon-pressure-overload-a-longitudinal-in-vivo-pet-mri-and-mrs-study-on-cardiac-metabolic-structural-and-functional-adaptations
#17
Desiree Abdurrachim, Miranda Nabben, Verena Hoerr, Michael T Kuhlmann, Philipp Bovenkamp, Jolita Ciapaite, Ilvy M E Geraets, Will Coumans, Joost J F P Luiken, Jan F C Glatz, Michael Schäfers, Klaas Nicolay, Cornelius Faber, Sven Hermann, Jeanine J Prompers
Aim: Heart failure is associated with altered myocardial substrate metabolism and impaired cardiac energetics. Comorbidities like diabetes may influence the metabolic adaptations during heart failure development. We quantified to what extent changes in substrate preference, lipid accumulation, and energy status predict the longitudinal development of hypertrophy and failure in the non-diabetic and the diabetic heart. Methods and results: Transverse aortic constriction (TAC) was performed in non-diabetic ( db /+) and diabetic ( db/db ) mice to induce pressure overload...
May 26, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28548942/the-n-terminal-tail-coordinates-with-carbohydrate-recognition-domain-to-mediate-galectin-3-induced-apoptosis-in-t-cells
#18
Huiting Xue, Lu Liu, Zihan Zhao, Zhongyu Zhang, Yuan Guan, Hairong Cheng, Yifa Zhou, Guihua Tai
Galectin-3 is a galectin with a unique flexible N-terminal tail (NT) connected to the conserved carbohydrate recognition domain (CRD). Galectin-3 is associated with tumor immune tolerance and exhibits an ability to induce T cell apoptosis. We used Jurkat, Jurkat E6-1 and CEM T-cell lines and human peripheral blood mononuclear cells (PBMCs) to investigate the specific roles of the CRD and NT in inducing T cell apoptosis. Galectin-3 triggered sustained extracellular signal-regulated kinase (ERK) phosphorylation that induced apoptosis...
May 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28548702/p16-loss-and-e2f-cell-cycle-deregulation-in-infant-posterior-fossa-ependymoma
#19
Seth C Lummus, Andrew M Donson, Katherine Gowan, Kenneth L Jones, Rajeev Vibhakar, Nicholas K Foreman, B K Kleinschmidt-DeMasters
BACKGROUND: Posterior fossa (PF) ependymomas (EPNs) in infants less than 1 year of age (iEPN-PF) have a poorer clinical outcome than EPNs in older children. While radiation therapy is the standard of care for the latter, it is withheld in infants to avoid neurotoxicity to immature brain. It is unknown whether the adverse outcome in iEPN-PFs is due to treatment differences or aggressive biology. We examined this question using molecular profiling. METHODS: Six anaplastic iEPN-PFs were subjected to transcriptomic analysis and FISH for p16 loss and gains of 1q, and compared with anaplastic PF EPNs from older children...
May 26, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28546787/pepsinogen-c-expression-regulation-and-its-relationship-with-cancer
#20
REVIEW
Shixuan Shen, Jingyi Jiang, Yuan Yuan
Pepsinogen C (PGC) belongs to the aspartic protease family and is secreted by gastric chief cells. PGC could be activated to pepsin C and digests polypeptides and amino acids, but as a zymogen PGC's functions is unclear. In normal physiological conditions, PGC is initially detected in the late embryonic stage and is mainly expressed in gastric mucosa. The in situ expression of PGC in gastric mucosa is decreased considerably in the process of superficial gastritis → atrophic gastritis → gastric cancer (GC), proving that PGC is a comparatively ideal negative marker of GC...
2017: Cancer Cell International
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