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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
#1
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
#2
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
#3
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 (e.g. 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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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-pre-megakaryocytic-erythroid-output-and-maintains-survival-of-megakaryocyte-progenitors
#10
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 two 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 (HSPCs). RUNX1B expression is more restricted, being highly expressed in the megakaryocyte lineage but downregulated during erythropoiesis...
May 10, 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
#11
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
#12
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...
April 28, 2017: Endocrinology
https://www.readbyqxmd.com/read/28457938/parp-inhibition-protects-mitochondria-and-reduces-ros-production-via-parp-1-atf4-mkp-1-mapk-retrograde-pathway
#13
Eniko Hocsak, Viktor Szabo, Nikoletta Kalman, Csenge Antus, Anna Cseh, Katalin Sumegi, Krisztian Eros, Zoltan Hegedus, Ferenc Gallyas, Balazs Sumegi, Boglarka Racz
Oxidative stress induces DNA breaks and PARP-1 activation which initiates mitochondrial reactive oxygen species (ROS) production and cell death through pathways not yet identified. Here, we show the mechanism by which PARP-1 influences these processes via PARylation of activating transcription factor-4 (ATF4) responsible for MAP kinase phosphatase-1 (MKP-1) expression and thereby regulates MAP kinases. PARP inhibitor, or silencing, of PARP induced MKP-1 expression by ATF4-dependent way, and inactivated JNK and p38 MAP kinases...
April 27, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28444485/evaluation-of-kinetic-programs-in-various-automated-perimeters
#14
Shigeki Hashimoto, Chota Matsumoto, Mariko Eura, Sachiko Okuyama, Yoshikazu Shimomura
PURPOSE: Kinetic programs in four automated perimeters were evaluated and compared for their clinical usefulness using four simulated visual field (VF) patterns. METHODS: Using the results of conventional Goldmann manual kinetic perimetry (MKP), simulated fields with concentric contraction, a temporal residual island only, a small central island with a temporal island, and a ring scotoma were created. Four kinetic programs, Humphrey 750i Kinetic Test (Humphrey), OCULUS Twinfield 2 Kinetic Perimetry (OCULUS), OCTOPUS 900 Goldmann Kinetic Perimetry (OCTOPUS GKP), and Kowa AP-7000 Isopter (Kowa) were tested by the 4 simulated defect patterns using stimuli of V/4e, I/4e, I/3e, I/2e, and I/1e at speeds of 3 and 5°/s...
April 25, 2017: Japanese Journal of Ophthalmology
https://www.readbyqxmd.com/read/28438162/targeting-of-nicotinamide-phosphoribosyltransferase-enzymatic-activity-ameliorates-lung-damage-induced-by-ischemia-reperfusion-in-rats
#15
Geng-Chin Wu, Wen-I Liao, Shu-Yu Wu, Hsin-Ping Pao, Shih-En Tang, Min-Hui Li, Kun-Lun Huang, Shi-Jye Chu
BACKGROUND: Emerging evidence reveals that nicotinamide phosphoribosyltransferase (NAMPT) has a significant role in the pathophysiology of the inflammatory process. NAMPT inhibition has a beneficial effect in the treatment of a variety of inflammatory diseases. However, it remains unclear whether NAMPT inhibition has an impact on ischemia-reperfusion (I/R)-induced acute lung injury. In this study, we examined whether NAMPT inhibition provided protection against I/R lung injury in rats...
April 24, 2017: Respiratory Research
https://www.readbyqxmd.com/read/28429785/natriuretic-peptide-receptor-guanylyl-cyclase-a-pathway-counteracts-glomerular-injury-evoked-by-aldosterone-through-p38-mitogen-activated-protein-kinase-inhibition
#16
Yukiko Kato, Kiyoshi Mori, Masato Kasahara, Keisuke Osaki, Akira Ishii, Keita P Mori, Naohiro Toda, Shoko Ohno, Takashige Kuwabara, Takeshi Tokudome, Ichiro Kishimoto, Moin A Saleem, Taiji Matsusaka, Kazuwa Nakao, Masashi Mukoyama, Motoko Yanagita, Hideki Yokoi
Guanylyl cyclase-A (GC-A) signaling, a natriuretic peptide receptor, exerts renoprotective effects by stimulating natriuresis and reducing blood pressure. Previously we demonstrated massive albuminuria with hypertension in uninephrectomized, aldosterone-infused, and high salt-fed (ALDO) systemic GC-A KO mice with enhanced phosphorylation of p38 mitogen-activated protein kinase (MAPK) in podocytes. In the present study, we examined the interaction between p38 MAPK and GC-A signaling. The administration of FR167653, p38 MAPK inhibitor, reduced systolic blood pressure (SBP), urinary albumin excretion, segmental sclerosis, podocyte injury, and apoptosis...
April 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28414142/doxofylline-does-not-increase-formoterol-induced-camp-nor-mkp-1-expression-in-asm-cells-resulting-in-lack-of-anti-inflammatory-effect
#17
Brijeshkumar S Patel, Michael J Kugel, Gina Baehring, Alaina J Ammit
The xanthine doxofylline has been examined in clinical trials and shown to have efficacy and greater tolerability than theophylline in asthma and chronic obstructive pulmonary disease. The 'novofylline' doxofylline has demonstrated bronchodilatory and anti-inflammatory actions in in vivo and ex vivo experimental models of respiratory disease. However, there are limited studies in vitro. We address this herein and examine whether doxofylline has anti-inflammatory impact on primary cultures of airway smooth muscle (ASM) cells...
April 13, 2017: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28408478/antagonistic-roles-for-styx-pseudophosphatases-in-neurite-outgrowth
#18
REVIEW
Arya Dahal, Shantá D Hinton
Mitogen-activated protein kinases (MAPKs) are essential players in important neuronal signaling pathways including neuronal development, plasticity, survival, learning, and memory. The inactivation of MAPKs is tightly controlled by MAPK phosphatases (MKPs), which also are important regulators of these neuronal processes. Considering that MAPKs and MKPs are major players in neuronal signaling, it follows that their misregulation is pivotal in neurodegenerative diseases such as Alzheimer's, Huntington's, Parkinson's, and amyotrophic lateral sclerosis...
April 15, 2017: Biochemical Society Transactions
https://www.readbyqxmd.com/read/28405172/mitogen-activated-protein-kinase-phosphatase-3-mkp-3-in-the-surgical-wound-is-necessary-for-the-resolution-of-postoperative-pain-in-mice
#19
Sladjana Skopelja-Gardner, Madhurima Saha, Perla Abigail Alvarado-Vazquez, Brenna S Liponis, Elena Martinez, E Alfonso Romero-Sandoval
Mitogen-activated protein kinase (MAPK) phosphatase-3 (MKP-3) and its substrates (extracellular signal-regulated kinase [ERK] and p38) play an important role in pathophysiological mechanisms of acute postoperative and chronic neuropathic pain in the spinal cord. This study aimed to understand the role of MKP-3 and its target MAPKs at the site of surgical incision in nociceptive behavior. Wild-type (WT) and MKP-3 knockout (KO) mice underwent unilateral plantar hind paw incision. Mechanical allodynia was assessed by using von Frey filaments...
2017: Journal of Pain Research
https://www.readbyqxmd.com/read/28359564/cingulate-overexpression-of-mitogen-activated-protein-kinase-phosphatase-1-as-a-key-factor-for-depression
#20
Florent Barthas, Muris Humo, Ralf Gilsbach, Elisabeth Waltisperger, Meltem Karatas, Samuel Leman, Lutz Hein, Catherine Belzung, Anne-Laurence Boutillier, Michel Barrot, Ipek Yalcin
BACKGROUND: Depression is frequently associated with chronic pain or chronic stress. Among cortical areas, the anterior cingulate cortex (ACC, areas 24a and 24b) appears to be important for mood disorders and constitutes a neuroanatomical substrate for investigating the underlying molecular mechanisms. The current work aimed at identifying ACC molecular factors subserving depression. METHODS: Anxiodepressive-like behaviors in C57BL/6J male mice were induced by neuropathic pain, unpredictable chronic mild stress, and optogenetic ACC stimulation and were evaluated using novelty suppressed feeding, splash, and forced swim tests...
February 14, 2017: Biological Psychiatry
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