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https://www.readbyqxmd.com/read/28904347/oscillatory-dynamics-of-p38-activity-with-transcriptional-and-translational-time-delays
#1
Yuan Zhang, Haihong Liu, Fang Yan, Jin Zhou
Recent experimental evidence reports that oscillations of p38 MAPK (p38) activity would efficiently induce pro-inflammatory gene expression, which might be deleterious to immune systems and may even cause cellular damage and apoptosis. It is widely accepted now that transcriptional and translational delays are ubiquitous in gene expression, which can typically result in oscillatory responses of gene regulations. Consequently, delay-driven sustained oscillations in p38 activity (p38*) could in principle be commonplace...
September 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28876465/procyanidin-b2-3-3-di-o-gallate-induces-oxidative-stress-mediated-cell-death-in-prostate-cancer-cells-via-inhibiting-map-kinase-phosphatase-activity-and-activating-erk1-2-and-ampk
#2
Rahul Kumar, Gagan Deep, Michael F Wempe, Joseph Surek, Amit Kumar, Rajesh Agarwal, Chapla Agarwal
Neoplastic cells exhibit higher oxidative stress compared to normal cells; however, antioxidants based clinical trials have mostly failed. Another attractive therapeutic approach is to further increase the oxidative stress in cancer cells leading to cell death. Herein, we show that Procyanidin B2 3,3"-di-O-gallate (B2G2), the most active constituent of grape seed extract, treatment causes cell death in human prostate cancer (PCa) cells (LNCaP and 22Rv1) via increasing the reactive oxygen species (ROS) generation...
September 6, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28875323/evodiamine-inhibits-angiotensin-ii-induced-rat-cardiomyocyte-hypertrophy
#3
Na He, Qi-Hai Gong, Feng Zhang, Jing-Yi Zhang, Shu-Xian Lin, Hua-Hua Hou, Qin Wu, An-Sheng Sun
OBJECTIVE: To investigate the effects of evodiamine (Evo), a component of Evodiaminedia rutaecarpa Juss.) Benth, on cardiomyocyte hypertrophy induced by angiotensin II (Ang II) and further explore the potential mechanisms. METHODS: Cardiomyocytes from neonatal Sprague Dawley rats were isolated and characterized, and then the cadiomyocyte cultures were randomly divided into control, model (Ang II 0.1 μmol/L), and Evo (0.03, 0.3, 3 μmol/L) groups. The cardiomyocyte surface area, protein level, intracellular free calcium ([Ca(2+)]i) concentration, activity of nitric oxide synthase (NOS) and content of nitric oxide (NO) were measured, respectively...
September 5, 2017: Chinese Journal of Integrative Medicine
https://www.readbyqxmd.com/read/28866049/overexpression-of-mitogen-activated-protein-kinase-phosphatase-3-mkp-3-reduces-foxo1-phosphorylation-in-mice-hypothalamus
#4
Bárbara de Almeida Rodrigues, Gabriel Keine Kuga, Vitor Rosetto Muñoz, Rafael Calais Gaspar, Mariana Rosolen Tavares, José Diego Botezelli, Adelino Sanchez Ramos da Silva, Dennys Esper Cintra, Leandro Pereira de Moura, Fernando Moreira Simabuco, Eduardo Rochete Ropelle, José Rodrigo Pauli
The mitogen-activated kinase phosphatase-3 (MKP-3) has gained great importance in the scientific community by acting as a regulator of the cell cycle through dephosphorylation of FoxO1, an important transcription factor involved in the insulin intracellular signaling cascade. When dephosphorylated and translocated to the nuclei, FoxO1 can promote the transcription of orexigenic neuropeptides (NPY/AgRP) in the hypothalamus, whereas insulin signaling is responsible for the disruption of this process. However, it is not understood if the hypothalamic activation of MKP-3 affects FoxO1 phosphorylation, and we hypothesized that MKP-3 overexpression reduces the capacity of the insulin signal to phosphorylate FoxO1...
September 1, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28861806/rutaecarpine-inhibits-intimal-hyperplasia-in-a-balloon-injured-rat-artery-model
#5
Yang Xu, Xiu-Ping Chen, Feng Zhang, Hua-Hua Hou, Jing-Yi Zhang, Shu-Xian Lin, An-Sheng Sun
OBJECTIVE: To investigate the effect and potential mechanisms of rutaecarpine (Rut) in a rat artery balloon-injury model. METHODS: The intimal hyperplasia model was established by rubbing the endothelia with a balloon catheter in the common carotid artery (CCA) of rats. Fifty rats were randomly divided into fifive groups, ie. sham, model, Rut (25, 50 and 75 mg/kg) with 10 rats of each group. The rats were treated with or without Rut (25, 50, 75 mg/kg) by intragastric administration for 14 consecutive days following injury...
September 1, 2017: Chinese Journal of Integrative Medicine
https://www.readbyqxmd.com/read/28797290/role-and-regulation-of-mkp-1-in-airway-inflammation
#6
REVIEW
Seyed M Moosavi, Pavan Prabhala, Alaina J Ammit
Mitogen-activated protein kinase (MAPK) phosphatase 1 (MKP-1) is a protein with anti-inflammatory properties and the archetypal member of the dual-specificity phosphatases (DUSPs) family that have emerged over the past decade as playing an instrumental role in the regulation of airway inflammation. Not only does MKP-1 serve a critical role as a negative feedback effector, controlling the extent and duration of pro-inflammatory MAPK signalling in airway cells, upregulation of this endogenous phosphatase has also emerged as being one of the key cellular mechanism responsible for the beneficial actions of clinically-used respiratory medicines, including β2-agonists, phosphodiesterase inhibitors and corticosteroids...
August 10, 2017: Respiratory Research
https://www.readbyqxmd.com/read/28765831/the-dataset-describes-hif-1-%C3%AE-expression-and-lps-mediated-cytokine-production-in-mkp-1-deficient-bone-marrow-derived-murine-macrophages
#7
Harvinder Talwar, Christian Bauerfeld, Yusen Liu, Lobelia Samavati
The data presented in this article are related to the research article entitled "MKP-1 negatively regulates LPS-mediated IL-1β production through p38 activation and HIF-1α expression" (Talwar et al., 2017) [1]. This data describes that LPS-mediated p38 and JNK phosphorylation is enhanced in MKP-1 deficient macrophages. HIF-1α expression and its nuclear accumulation are significantly increased in the nuclear extracts of MKP-1 deficient BMDMs. MKP-1 deficient BMDMs exhibited higher expression of the coactivator p300 of HIF-1α both at baseline and after LPS challenge...
October 2017: Data in Brief
https://www.readbyqxmd.com/read/28746931/treatment-outcomes-for-metastatic-melanoma-of-unknown-primary-in-the-new-era-a-single-institution-study-and-review-of-the-literature
#8
Kierstin Utter, Chloe Goldman, Sarah A Weiss, Richard L Shapiro, Russell S Berman, Melissa Ann Wilson, Anna C Pavlick, Iman Osman
BACKGROUND: Metastatic melanoma of unknown primary (MUP) is uncommon, biologically ill defined, and clinically understudied. MUP outcomes are seldom reported in clinical trials. In this study, we analyze responses of MUP patients treated with systemic therapy in an attempt to inform treatment guidelines for this unique population. METHODS: New York University (NYU)'s prospective melanoma database was searched for MUP patients treated with systemic therapy. PubMed and Google Scholar were searched for MUP patients treated with immunotherapy or targeted therapy reported in the literature, and their response and survival data were compared to the MUP patient data from NYU...
July 27, 2017: Oncology
https://www.readbyqxmd.com/read/28679626/the-bradykinin-bk-cgmp-pkg-pathway-augments-insulin-sensitivity-via-upregulation-of-mapk-phosphatase-5-and-inhibition-of-jun-kinase-jnk
#9
Maria E Frigolet, Garry Thomas, Kristin Beard, Huogen Lu, Lijiang Liu, I George Fantus
Bradykinin (BK) promotes insulin sensitivity and glucose uptake in adipocytes and other cell types. We demonstrated that in rat adipocytes BK enhances insulin-stimulated glucose transport via endothelial nitric oxide synthase (eNOS), nitric oxide (NO) generation, and decreased activity of the mitogen activated protein kinase (MAPK), JNK (c-Jun-N-terminal kinase). In endothelial cells, NO increases soluble guanylate cyclase (sGC) activity which in turn, activates protein kinase G (PKG) by increasing cGMP levels...
July 5, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28674403/characterization-and-reversal-of-doxorubicin-mediated-biphasic-activation-of-erk-and-persistent-excitability-in-sensory-neurons-of-aplysia-californica
#10
Harini Lakshminarasimhan, Brittany L Coughlin, Amber S Darr, John H Byrne
Doxorubicin (DOX), a common chemotherapeutic agent, impairs synaptic plasticity. DOX also causes a persistent increase in basal neuronal excitability, which occludes serotonin-induced enhanced excitability. Therefore, we sought to characterize and reverse DOX-induced physiological changes and modulation of molecules implicated in memory induction using sensory neurons from the marine mollusk Aplysia californica. DOX produced two mechanistically distinct phases of extracellular signal-regulated kinase (ERK) activation, an early and a late phase...
July 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28657665/obacunone-causes-sustained-expression-of-mkp-1-thus-inactivating-p38-mapk-to-suppress-pro-inflammatory-mediators-through-intracellular-mif
#11
Yuan Gao, Rui Hou, Fen Liu, Haibo Liu, Qiaoling Fei, Yixin Han, Runlan Cai, Cheng Peng, Yun Qi
Obacunone (OBA) is a highly oxygenated triterpenoid with various pharmacological activities. In this study, we explored its anti-inflammatory effect and underlying mechanisms in LPS-activated macrophages. Our data showed that OBA potently decreased pro-inflammatory mediators (eg, NO, IL-6, IL-1β, and MCP-1) at the transcriptional and translational levels without cytotoxicity. A mechanism study showed that OBA significantly suppressed p38-mediated AP-1 signaling by stabilizing the mRNA of mitogen-activated protein kinase phosphatase 1 (MKP-1), thus prolonging the expression time of the MKP-1 protein...
June 28, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28650468/mkp-1-suppresses-parp-1-degradation-to-mediate-cisplatin-resistance
#12
J Wang, D H Kho, J-Y Zhou, R J Davis, G S Wu
Understanding the mechanisms of platinum compound resistance, including cisplatin resistance, has important implications for improving cancer treatments. Previous studies identified a potential role for mitogen-activated protein kinase phosphatase-1 (MKP-1) in cisplatin resistance. This work focuses on the regulation of poly(ADP-ribose) polymerase-1 (PARP-1) expression by MKP-1. We found that MKP-1 overexpression stimulates PARP-1 and poly(ADP-ribose) (PAR) protein expression and cisplatin resistance while its downregulation suppresses PARP-1 and PAR protein expression and cisplatin resistance...
June 26, 2017: Oncogene
https://www.readbyqxmd.com/read/28619580/corrigendum-to-mkp-1-negatively-regulates-lps-mediated-il-1%C3%AE-production-through-p38-activation-and-hif-1%C3%AE-expression-cell-signal-34-1-10-2017-epub-2017-feb-24
#13
H Talwar, C Bauerfeld, M Bouhamdan, P Farshi, Y Liu, L Samavati
No abstract text is available yet for this article.
June 12, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28551880/the-role-of-mkp-1-in-insulin-induced-cardioprotection
#14
Ingrid Webster, Angelique Smith, Amanda Lochner, Barbara Huisamen
PURPOSE: The mitogen-activated protein kinase phosphatases (MKPs) are a family of dual-specificity phosphatases that inactivate MAPKs by dephosphorylation. Impairment of MKP-1 expression in insulin resistance has been suggested to affect the cardioprotective properties of insulin. We hypothesized that manipulation of its activity during myocardial ischaemia/reperfusion of control as well as insulin-resistant rats may affect the outcome. METHODS: Hearts from 16 week dietary induced obese Wistar rats and their age matched controls were isolated, perfused in the working mode and subjected to 15 min global ischaemia / 30 min reperfusion or 35 min coronary artery ligation/ 60 min reperfusion...
May 27, 2017: Cardiovascular Drugs and Therapy
https://www.readbyqxmd.com/read/28550735/clarithromycin-inhibits-tnf-%C3%AE-induced-muc5ac-mucin-gene-expression-via-the-mkp-1-p38mapk-dependent-pathway
#15
Said Ahmad Shah, Hajime Ishinaga, Kazuhiko Takeuchi
Clarithromycin is a 14-membered macrolide antibiotic. Low-dose, long-term macrolide therapy is effective in patients with chronic airway diseases, such as diffuse panbronchitis, chronic bronchitis, and chronic sinusitis. However, the mechanism underlying this clinical efficacy remains unclear. The dual specificity phosphatase MKP-1 (MAPK phosphatase-1), also called DUSP (dual specificity phosphatase-1), was initially identified as an in vitro ERK-specific phosphatase, but depending on the cell type, it can also dephosphorylate other members of the MAPK family, such as p38 and JNK, and thus suppress downstream signaling of these kinases...
May 24, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28550662/-effects-of-simvastatin-on-the-proliferation-invasion-and-radiosensitivity-in-lewis-lung-cancer-cell-line
#16
S F Yu, J Cheng, S Geng, S Gao
Objective: To investigate the effects of simvastatin on proliferation, invasion and radiosensitivity of mouse Lewis lung cancer cell line in vitro. Methods: The inhibitory effects of simvastatin on proliferation of Lewis lung cancer cells were detected by MTT assay. Matrigel invasion and migration assay was used to determine the invasion and motility ability of the Lewis cells. P38 activity was measured by p38 activity detection kit, and the expressions of p-p38, MKP-1, RhoA and MMP-2 were analyzed by Western blot...
April 23, 2017: Zhonghua Zhong Liu za Zhi [Chinese Journal of Oncology]
https://www.readbyqxmd.com/read/28504466/nepetoidin-b-a-natural-product-inhibits-lps-stimulated-nitric-oxide-production-via-modulation-of-inos-mediated-by-nf-%C3%AE%C2%BAb-mkp-5-pathways
#17
Xiaxia Wu, Hongwei Gao, Wen Sun, Jie Yu, Hao Hu, Qiongming Xu, Xiuping Chen
Previous reports showed that nepetoidin B (NTB), a natural product isolated from many herbs, has anti-fungal and anti-bacterial effects. In this study, the antiinflammatory effect of NTB was investigated in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. The cytotoxic effect of NTB and LPS was determined by MTT assay. The nitric oxide (NO) production was detected by Griess assay. The TNF-α and IL-6 levels were determined by enzyme-linked immunosorbent assay kits. Protein expressions were tested by western blotting...
May 15, 2017: Phytotherapy Research: PTR
https://www.readbyqxmd.com/read/28490570/mouse-runx1c-regulates-premegakaryocytic-erythroid-output-and-maintains-survival-of-megakaryocyte-progenitors
#18
Julia E Draper, Patrycja Sroczynska, Hui Sun Leong, Muhammad Z H Fadlullah, Crispin Miller, Valerie Kouskoff, Georges Lacaud
RUNX1 is crucial for the regulation of megakaryocyte specification, maturation, and thrombopoiesis. Runx1 possesses 2 promoters: the distal P1 and proximal P2 promoters. The major protein isoforms generated by P1 and P2 are RUNX1C and RUNX1B, respectively, which differ solely in their N-terminal amino acid sequences. RUNX1C is the most abundantly expressed isoform in adult hematopoiesis, present in all RUNX1-expressing populations, including the cKit(+) hematopoietic stem and progenitor cells. RUNX1B expression is more restricted, being highly expressed in the megakaryocyte lineage but downregulated during erythropoiesis...
July 20, 2017: Blood
https://www.readbyqxmd.com/read/28487811/curcumin-inhibits-nthi-induced-muc5ac-mucin-overproduction-in-otitis-media-via-upregulation-of-mapk-phosphatase-mkp-1
#19
Anuhya Sharma Konduru, Shingo Matsuyama, Byung-Cheol Lee, Kensei Komatsu, Jian-Dong Li
Otitis media (OM), characterized by the presence of mucus overproduction and excess inflammation in the middle ear, is the most common childhood infection. Nontypeable Haemophilus influenzae (NTHi) pathogen is responsible for approximately one-third of episodes of bacteria-caused OM. Current treatments for bacterial OM rely on the systemic use of antibiotics, which often leads to the emergence of multidrug resistant bacterial strains. Therefore there is an urgent need for developing alternative therapies strategies for controlling mucus overproduction in OM...
2017: International Journal of Inflammation
https://www.readbyqxmd.com/read/28460125/how-protein-kinase-a-activates-canonical-tyrosine-kinase-signaling-pathways-to-promote-granulosa-cell-differentiation
#20
Nathan C Law, Elyse M Donaubauer, Anthony J Zeleznik, Mary Hunzicker-Dunn
Protein kinase A (PKA) has recently been shown to mimic the actions of follicle-stimulating hormone (FSH) by activating signaling pathways that promote granulosa cell (GC) differentiation, such as phosphatidylinositol 3-kinase (PI3K) and mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK). We sought to elucidate the mechanism by which PKA, a Ser/Thr kinase, intersected the PI3K/AKT and MAPK/ERK pathways that are canonically activated by receptor tyrosine kinases (RTKs). Our results show that for both of these pathways, the RTK is active in the absence of FSH yet signaling down the pathways to commence transcriptional responses requires FSH-stimulated PKA activation...
July 1, 2017: Endocrinology
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