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https://www.readbyqxmd.com/read/28129433/celastrol-ameliorates-cd-induced-neuronal-apoptosis-by-targeting-nox2-derived-ros-dependent-pp5-jnk-signaling-pathway
#1
Chong Xu, Xiaoxue Wang, Chenjian Gu, Hai Zhang, Ruijie Zhang, Xiaoqing Dong, Chunxiao Liu, Xiaoyu Hu, Xiang Ji, Shile Huang, Long Chen
Celastrol, a plant-derived triterpene, has neuroprotective benefit in the models of neurodegenerative disorders that are characterized by overproduction of reactive oxygen species (ROS). Recently, we have reported that cadmium (Cd) activates c-Jun N-terminal kinase (JNK) pathway leading to neuronal cell death by inducing ROS inactivation of protein phosphatase 5 (PP5), and celastrol prevents Cd-activated JNK pathway against neuronal apoptosis. Therefore, we hypothesized that celastrol could hinder Cd induction of ROS-dependent PP5-JNK signaling pathway from apoptosis in neuronal cells...
January 27, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28096467/mir-21-mediated-radioresistance-is-via-promoting-repair-of-dna-double-strand-breaks
#2
Baocheng Hu, Xiang Wang, Suofeng Hu, Xiaomin Ying, Ping Wang, Xiangming Zhang, Jian Wang, Hongyan Wang, Ya Wang
MiR-21 as an oncogene that over-expresses in most human tumors involves radioresistance; however, the mechanism remains unclear. Here, we demonstrate that miR-21-mediated radioresistance is through promoting repair of DNA double strand breaks, which includes to facilitate both non-homologous end-joining (NHEJ) and homologous recombination repair (HRR). The miR-21-promoted NHEJ is through targeting GSK3B (a novel target of miR-21) that affects the CRY2/PP5 pathway and in turn increases DNA-PKcs activity. The miR-21-promoted HRR is through targeting both GSK3B and CDC25A (a known target of miR-21), which neutralizes the effects of targeting GSK3B-induced CDC25A increase since GSK3B promotes degradation of both CDC25A and Cyclin D1, but CDC25A and Cyclin D1 have an opposite effect on HRR...
January 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28090608/elevated-expression-of-serine-threonine-phosphatase-type-5-correlates-with-malignant-proliferation-in-human-osteosarcoma
#3
Kun Han, Zhihua Gan, Shuchen Lin, Haiyan Hu, Zan Shen, Daliu Min
Osteosarcoma is the most common primary malignant bone tumor in adolescents and young adults. However, the involvement of serine/threonine phosphatase type 5 (PP5) in osteosarcoma remains unclear. The aim of this study was to evaluate the functional role of PP5 in osteosarcoma cells. Firstly, we found that PP5 is widely expressed in several human osteosarcoma cell lines. Then we used lentivirus-delivered siRNA to silence PP5 expression in Saos-2 and U2OS cell lines. Knockdown of endogenous PP5 expression by shRNA-expressing lentivirus significantly decreased the viability and proliferation of the osteosarcoma cells...
January 13, 2017: Acta Biochimica Polonica
https://www.readbyqxmd.com/read/27886809/small-mammal-utilization-by-middle-stone-age-humans-at-die-kelders-cave-1-and-pinnacle-point-site-5-6-western-cape-province-south-africa
#4
Aaron Armstrong
Reported here are the results of a taphonomic analysis of the small mammals (between 0.75 kg and 4.5 kg adult body weight) and size 1 bovids (≤20 kg adult body weight) from the Middle Stone Age (MSA) sites of Die Kelders Cave 1 (DK1) and Pinnacle Point Site 5-6 (PP5-6), Western Cape Province, South Africa. This study provides a comprehensive taphonomic analysis of MSA small mammals with a focus on discerning the role of humans in their accumulation and the implications for human behavioral adaptations...
December 2016: Journal of Human Evolution
https://www.readbyqxmd.com/read/27827901/structure-activity-relationship-studies-using-natural-and-synthetic-okadaic-acid-dinophysistoxin-toxins
#5
Michael J Twiner, Gregory J Doucette, Yucheng Pang, Chao Fang, Craig J Forsyth, Christopher O Miles
Okadaic acid (OA) and the closely related dinophysistoxins (DTXs) are algal toxins that accumulate in shellfish and are known serine/threonine protein phosphatase (ser/thr PP) inhibitors. Phosphatases are important modulators of enzyme activity and cell signaling pathways. However, the interactions between the OA/DTX toxins and phosphatases are not fully understood. This study sought to identify phosphatase targets and characterize their structure-activity relationships (SAR) with these algal toxins using a combination of phosphatase activity and cytotoxicity assays...
November 4, 2016: Marine Drugs
https://www.readbyqxmd.com/read/27784696/serine-threonine-phosphatases-and-aquaporin-2-regulation-in-renal-collecting-duct
#6
Sophia M LeMaire, Viswanathan Raghuram, Cameron R Grady, Christina M Pickering, Chung-Lin Chou, Ezigbobiara N Umejiego, Mark A Knepper
Phosphorylation of the aquaporin-2 (AQP2) water channel at four COOH-terminal serines plays a central role in the regulation of water permeability of the renal collecting duct. The level of phosphorylation at these sites is determined by a balance between phosphorylation by protein kinases and dephosphorylation by phosphatases. The phosphatases that dephosphorylate AQP2 have not been identified. Here, we use large-scale data integration techniques to identify serine-threonine phosphatases likely to interact with AQP2 in renal collecting duct principal cells...
January 1, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/27742828/cytokine-induced-glucocorticoid-resistance-from-eosinophil-activation-protein-phosphatase-5-modulation-of-glucocorticoid-receptor-phosphorylation-and-signaling
#7
Konrad Pazdrak, Christof Straub, Rosario Maroto, Susan Stafford, Wendy I White, William J Calhoun, Alexander Kurosky
The mechanisms contributing to persistent eosinophil activation and poor eosinopenic response to glucocorticoids in severe asthma are poorly defined. We examined the effect of cytokines typically overexpressed in the asthmatic airways on glucocorticoid signaling in in vitro activated eosinophils. An annexin V assay used to measure eosinophil apoptosis showed that cytokine combinations of IL-2 plus IL-4 as well as TNF-α plus IFN-γ, or IL-3, GM-CSF, and IL-5 alone significantly diminished the proapoptotic response to dexamethasone...
November 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27687725/protein-phosphatase-pp5-controls-bone-mass-and-the-negative-effects-of-rosiglitazone-on-bone-through-reciprocal-regulation-of-ppar%C3%AE-peroxisome-proliferator-activated-receptor-%C3%AE-and-runx2-runt-related-transcription-factor-2
#8
Lance A Stechschulte, Chunxi Ge, Terry D Hinds, Edwin R Sanchez, Renny T Franceschi, Beata Lecka-Czernik
Peroxisome proliferator-activated receptor γ (PPARγ) and runt-related transcription factor 2 (RUNX2) are key regulators of mesenchymal stem cell (MSC) differentiation toward adipocytes and osteoblasts, respectively. Post-translational modifications of these factors determine their activities. Dephosphorylation of PPARγ at Ser-112 is required for its adipocytic activity, whereas phosphorylation of RUNX2 at serine 319 (Ser-319) promotes its osteoblastic activity. Here we show that protein phosphatase 5 (PP5) reciprocally regulates each receptor by targeting each serine...
November 18, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27628691/an-ultra-high-throughput-screen-for-catalytic-inhibitors-of-serine-threonine-protein-phosphatases-types-1-and-5-pp1c-and-pp5c
#9
Mark Swingle, Claude-Henry Volmar, S Adrian Saldanha, Peter Chase, Christina Eberhart, Edward A Salter, Brandon D'Arcy, Chad E Schroeder, Jennifer E Golden, Andrzej Wierzbicki, Peter Hodder, Richard E Honkanen
Although there has been substantial success in the development of specific inhibitors for protein kinases, little progress has been made in the identification of specific inhibitors for their protein phosphatase counterparts. Inhibitors of PP1 and PP5 are desired as probes for research and to test their potential for drug development. We developed and miniaturized (1536-well plate format) nearly identical homogeneous, fluorescence intensity (FLINT) enzymatic assays to detect inhibitors of PP1 or PP5. The assays were used in an ultra-high-throughput screening (uHTS) campaign, testing >315,000 small-molecule compounds...
September 14, 2016: Journal of Biomolecular Screening
https://www.readbyqxmd.com/read/27600583/oxidative-stress-impairs-the-stimulatory-effect-of-s100-proteins-on-protein-phosphatase-5-activity
#10
Fuminori Yamaguchi, Mitsumasa Tsuchiya, Seiko Shimamoto, Tomohito Fujimoto, Hiroshi Tokumitsu, Masaaki Tokuda, Ryoji Kobayashi
Oxidative stress is the consequence of an imbalance between the production of harmful reactive oxygen species and the cellular antioxidant system for neutralization, and it activates multiple intracellular signaling pathways, including apoptosis signal-regulating kinase 1 (ASK1). Protein phosphatase 5 (PP5) is a serine/threonine phosphatase involved in oxidative stress responses. Previously, we reported that S100 proteins activate PP5 in a calcium-dependent manner. S100 proteins belong to a family of small EF-hand calcium-binding proteins involved in many processes such as cell proliferation, differentiation, apoptosis, and inflammation...
2016: Tohoku Journal of Experimental Medicine
https://www.readbyqxmd.com/read/27565380/phosphorylated-tandembp-a-unique-protein-substrate-for-protein-phosphatase-assay
#11
Yasunori Sugiyama, Sho Yamashita, Yuuki Uezato, Yukako Senga, Syouichi Katayama, Naoki Goshima, Yasushi Shigeri, Noriyuki Sueyoshi, Isamu Kameshita
To analyze a variety of protein phosphatases, we developed phosphorylated TandeMBP (P-TandeMBP), in which two different mouse myelin basic protein isoforms were fused in tandem, as a protein phosphatase substrate. P-TandeMBP was prepared efficiently in four steps: (1) phosphorylation of TandeMBP by a protein kinase mixture (Ca(2+)/calmodulin-dependent protein kinase Iδ, casein kinase 1δ, and extracellular signal-regulated kinase 2); (2) precipitation of both P-TandeMBP and protein kinases to remove ATP, Pi, and ADP; (3) acid extraction of P-TandeMBP with HCl to remove protein kinases; and (4) neutralization of the solution that contains P-TandeMBP with Tris...
November 15, 2016: Analytical Biochemistry
https://www.readbyqxmd.com/read/27501780/protein-phosphatase-5-mediates-corticosteroid-insensitivity-in-airway-smooth-muscle-in-patients-with-severe-asthma
#12
L Chachi, M Abbasian, A Gavrila, A Alzahrani, O Tliba, P Bradding, A J Wardlaw, C Brightling, Y Amrani
BACKGROUND: The mechanisms driving glucocorticoid (GC) insensitivity in patients with severe asthma are still unknown. Recent evidence suggests the existence of GC-insensitive pathways in airway smooth muscle (ASM) caused by a defect in GC receptor (GRα) function. We examined whether other mechanisms could potentially explain the reduced sensitivity of ASM cells to GC in severe asthmatics. METHODS: Airway smooth muscle cells from healthy and severe asthmatic subjects were treated with TNF-α and responses to corticosteroids in both cohorts were compared by ELISA, immunoblot, immunohistochemistry and real-time PCR...
January 2017: Allergy
https://www.readbyqxmd.com/read/27466404/structural-and-functional-basis-of-protein-phosphatase-5-substrate-specificity
#13
Jasmeen Oberoi, Diana M Dunn, Mark R Woodford, Laura Mariotti, Jacqualyn Schulman, Dimitra Bourboulia, Mehdi Mollapour, Cara K Vaughan
The serine/threonine phosphatase protein phosphatase 5 (PP5) regulates hormone- and stress-induced cellular signaling by association with the molecular chaperone heat shock protein 90 (Hsp90). PP5-mediated dephosphorylation of the cochaperone Cdc37 is essential for activation of Hsp90-dependent kinases. However, the details of this mechanism remain unknown. We determined the crystal structure of a Cdc37 phosphomimetic peptide bound to the catalytic domain of PP5. The structure reveals PP5 utilization of conserved elements of phosphoprotein phosphatase (PPP) structure to bind substrate and provides a template for many PPP-substrate interactions...
August 9, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27412486/which-airway-pressure-should-be-applied-during-breath-hold-in-dogs-undergoing-thoracic-computed-tomography
#14
Alessandro Guarracino, Luca Lacitignola, Edoardo Auriemma, Valentina De Monte, Salvatore Grasso, Antonio Crovace, Francesco Staffieri
This randomized controlled trial study aimed to identify the optimal positive pressure (PP) level that can clear atelectasis while avoiding pulmonary hyperinflation during the breath-hold technique in dogs undergoing thoracic computed tomography (CT). Sixty dogs affected by mammary tumors undergoing thoracic CT for the screening of pulmonary metastases were randomly assigned to six groups with different levels of PP during the breath-hold technique: 0 (control), 5 (PP5), 8 (PP8), 10 (PP10), 12 (PP12), and 15 (PP15) cmH2 O...
September 2016: Veterinary Radiology & Ultrasound
https://www.readbyqxmd.com/read/26941058/effect-of-silibinin-and-vitamin-e-on-the-ask1-p38-mapk-pathway-in-d-galactosamine-lipopolysaccharide-induced-hepatotoxicity
#15
Reem M Hashem, Kamel Ma Hassanin, Laila A Rashed, Mohamed O Mahmoud, Mohamed G Hassan
Apoptosis signal-regulating kinase 1 (ASK1), a redox-sensor mitogen-activated protein kinase kinase kinase (MAPKKK) that activates p38 MAPK pathways in oxidative stress-induced hepatotoxicity in D-galactosamine/lipopolysaccharide (D-GalN/LPS) model, is a key central pathway in which specific targeting of ASK1 deactivation is of a great therapeutic potential. We tested the effect of silibinin and vitamin E in curative and prophylactic manner of treatment on the negative modulators of ASK1, thioredoxin1 (Trx1), thioredoxin reductase1 (TrxR1), and the protein phosphatase (PP5), whereas they have previously proven to have hepatoprotective effect...
June 2016: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/26870184/knockdown-of-protein-phosphatase-5-inhibits-ovarian-cancer-growth-in-vitro
#16
Xiaojiao Zheng, Lianxiao Zhang, Bohong Jin, Fubin Zhang, Duoyi Zhang, Lining Cui
Ovarian cancer is the most common cause of gynecological cancer-related mortality. Serine/threonine protein phosphatase 5 (PP5, PPP5C) has been recognized to be involved in the regulation of multiple cellular signaling cascades that control diverse cellular processes, including cell growth, differentiation, proliferation, motility and apoptosis. In this study, to evaluate the functional role of PP5 in ovarian cancer cells, lentivirus-mediated RNA interference (RNAi) was applied to silence PPP5C in the human ovarian cancer cell line CAOV-3...
January 2016: Oncology Letters
https://www.readbyqxmd.com/read/26545043/a-circle-has-no-end-role-of-cyclic-topology-and-accompanying-structural-reorganization-on-the-hole-distribution-in-cyclic-and-linear-poly-p-phenylene-molecular-wires
#17
Marat R Talipov, Ramesh Jasti, Rajendra Rathore
π-Conjugated organic oligomers/polymers hold great promise as long-range charge-transfer materials for modern photovoltaic applications. However, a set of criteria for the rational design of functional materials is not yet available, in part because of a lack of understanding of charge distribution in extended π-conjugated systems of different topologies, and concomitant effects on redox and optical properties. Herein we demonstrate the role of cyclic versus linear topology in controlling the redox/optical properties and hole distribution in poly-p-phenylenes (PPs) with the aid of experiment, computation, and our recently developed multistate parabolic model (MPM)...
December 2, 2015: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/26381179/dna-pkcs-interference-sensitizes-colorectal-cancer-cells-to-a-mtor-kinase-inhibitor-way-600
#18
Ling Wu, Jiansheng Zhang, Huiguo Wu, Enkun Han
Colorectal cancer (CRC) is one leading contributor of cancer-related mortalities. Mammalian target of rapamycin (mTOR), existing in two complexes (mTORC1/2), is a valuable target for possible CRC interference. In the current study, we showed that WAY-600, a potent mTOR inhibitor, only exerted moderate activity against primary and HT-29 CRC cells. We proposed that DNA-dependent protein kinase catalytic subunit (DNA-PKcs) could be the major resistance factor of WAY-600 in CRC cells. DNA-PKcs inhibitors, including NU7026 and NU7441, dramatically enhanced WAY-600-induced cytotoxic and pro-apoptotic effect against the CRC cells...
October 23, 2015: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/26224894/steroid-receptor-associated-immunophilins-a-gateway-to-steroid-signalling
#19
REVIEW
Thomas Ratajczak, Carmel Cluning, Bryan K Ward
The steroid receptor-associated immunophilins FKBP51, FKBP52, CyP40 and PP5 have specific roles in steroid receptor function that impact steroid hormone-binding affinity, nucleocytoplasmic shuttling and transcriptional activation of target genes in a tissue-specific manner. Aberrant expression of these functionally unique immunophilins has the potential to cause steroid-based diseases, including breast and prostate cancer, diabetes and related metabolic disorders, male and female infertility and major depressive disorders...
May 2015: Clinical Biochemist. Reviews
https://www.readbyqxmd.com/read/26190207/insights-into-the-key-interactions-between-human-protein-phosphatase-5-and-cantharidin-using-molecular-dynamics-and-site-directed-mutagenesis-bioassays
#20
Ji-Yuan Liu, Xi-En Chen, Ya-Lin Zhang
Serine/threonine protein phosphatase 5 (PP5) is a promising novel target for anticancer therapies. This work aims to uncover the key interactions at the atomic level between PP5 and three inhibitors (cantharidin, norcantharidin and endothall). We found that, unlike previous report, Arg 100 contributes less to PP5-inhibitor binding, and the residues His 69, Asn 128, His 129, Arg 225, His 252 and Arg 250 are of importance to PP5-inhibitor binding. The hydrophobic interactions established between the residues Val 254, Phe 271 and Tyr 276, especially Glu 253, are very important to enhance the inhibitive interaction...
2015: Scientific Reports
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