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https://www.readbyqxmd.com/read/29317435/skeletal-muscle-specific-deletion-of-mkp-1-reveals-a-p38-mapk-jnk-akt-signaling-node-that-regulates-obesity-induced-insulin-resistance
#1
Ahmed Lawan, Kisuk Min, Lei Zhang, Alberto Canfran-Duque, Michael J Jurczak, Joao Paulo G Camporez, Yaohui Nie, Timothy P Gavin, Gerald I Shulman, Carlos Hernandez-Fernando, Anton M Bennett
Stress responses promote obesity and insulin resistance, in part, by activating the stress-responsive mitogen-activated protein kinases (MAPKs), p38 MAPK and c-Jun NH2 kinase (JNK). Stress also induces expression of MAPK phosphatase-1 (MKP-1), which inactivates both JNK and p38 MAPK. However, the equilibrium between JNK/p38 MAPK and MKP-1 signaling in the development of obesity and insulin resistance is unclear. Skeletal muscle is a major tissue involved in energy expenditure and glucose metabolism. In skeletal muscle, MKP-1 is upregulated in high fat-diet fed mice and in skeletal muscle of obese humans...
January 9, 2018: Diabetes
https://www.readbyqxmd.com/read/29241671/mkp-1-protects-mice-against-toxin-induced-liver-damage-by-promoting-the-nrf2-cytoprotective-response
#2
Lin Luo, Yeru Chen, Hongyan Wang, Shengcun Wang, Kaihua Liu, Xin Li, Xiu Jun Wang, Xiuwen Tang
The present study was undertaken to investigate the possible protective effect of mitogen-activated protein kinase phosphatase 1 (Mkp-1) on toxin-induced hepatic injury. Here, we uncovered a positive feedback loop between Mkp-1, a dual threonine/tyrosine phosphatase, and nuclear factor erythroid 2-related factor 2 (Nrf2), a crucial regulator of the defense system in the liver. Mkp-1-/- mice exhibited decreased protein levels of Nrf2, phase II gene products, and reduced glutathione (GSH) in the liver. Induction of detoxifying enzymes by the Nrf2 activator butylated hydroxyanisole (BHA) or sulforaphane, was attenuated in the liver and small intestines of Mkp-1-/- mice, indicating that the Nrf2 signaling pathway is impaired as a result of Mkp-1 deficiency...
December 11, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/29226622/pde4-inhibitor-rolipram-inhibits-the-expression-of-microsomal-prostaglandin-e-synthase-1-by-a-mechanism-dependent-on-map-kinase-phosphatase-1
#3
Lauri Tuure, Mari Hämäläinen, Eeva Moilanen
Phosphodiesterase-4 (PDE4) inhibitors have recently been introduced to the treatment of COPD and psoriatic arthritis. Microsomal prostaglandin E synthase-1 (mPGES-1) is an inducible enzyme synthesizing PGE2 , the most abundant prostanoid related to inflammation and inflammatory pain. mPGES-1 is a potential drug target for novel anti-inflammatory treatments aiming at an improved safety profile as compared to NSAIDs. Here we investigated the effect of the PDE4 inhibitor rolipram on the expression of mPGES-1 in macrophages; and a potential mediator role in the process for MAP kinase phosphatase-1 (MKP-1) which is an endogenous factor limiting the activity of the proinflammatory MAP kinases p38 and JNK...
December 2017: Pharmacology Research & Perspectives
https://www.readbyqxmd.com/read/29165873/andrographolide-inhibits-hypoxia-induced-hypoxia-inducible-factor-1%C3%AE-and-endothelin-1-expression-through-the-heme-oxygenase-1-co-cgmp-mkp-5-pathways-in-ea-hy926-cells
#4
Hung-Chih Lin, Shih-Li Su, Wan-Chun Lin, Ai-Hsuan Lin, Ya-Chen Yang, Chong-Kuei Lii, Haw-Wen Chen
Andrographolide is a potent anti-inflammatory agent found in Andrographis paniculata. Endothelin 1 (ET-1) is an endothelium-derived vasoconstrictor with pro-inflammatory properties secreted in response to hypoxia. Mitogen-activated protein kinase phosphatase 5 (MKP-5) is a dual-specificity phosphatase that dephosphorylates threonine and tyrosine residues of MAPKs. We showed previously that hypoxia-induced HIF-1α expression and ET-1 secretion are dependent on p38 MAPK in EA.hy926 cells. Here, we investigate what role MKP-5 plays in andrographolide's inhibition of hypoxia-induced expression of HIF-1α and ET-1...
November 22, 2017: Environmental Toxicology
https://www.readbyqxmd.com/read/29143999/microrna-27a-3p-inhibits-cell-viability-and-migration-through-down-regulating-dusp16-in-hepatocellular-carcinoma
#5
Jin-Mao Li, Jun Zhou, Zhen Xu, Hai-Jin Huang, Min-Jiang Chen, Jian-Song Ji
MicroRNA (miRNA or miR) has been shown to play an important role in the initiation and development in many different cancers. Here, we demonstrated down-regulated expression of miR-27a-3p in hepatocellular carcinoma (HCC) tissues in comparison with that in adjacent normal liver tissues based on the TCGA database. Cells viability and apoptosis was measured by CCK-8 and flow cytometry assay. Cell invasion and migration was measured by Transwell and wound healing assay. The effect of miR-27a-3p on DUSP16 expression was evaluated by luciferase assays, and western blot assay...
November 16, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29141025/suppression-of-inflammatory-and-infection-responses-in-lung-macrophages-by-eucalyptus-oil-and-its-constituent-1-8-cineole-role-of-pattern-recognition-receptors-trem-1-and-nlrp3-the-map-kinase-regulator-mkp-1-and-nf%C3%AE%C2%BAb
#6
Niket Yadav, Harish Chandra
Eucalyptus oil (EO) used in traditional medicine continues to prove useful for aroma therapy in respiratory ailments; however, there is a paucity of information on its mechanism of action and active components. In this direction, we investigated EO and its dominant constituent 1,8-cineole (eucalyptol) using the murine lung alveolar macrophage (AM) cell line MH-S. In an LPS-induced AM inflammation model, pre-treatment with EO significantly reduced (P ≤0.01or 0.05) the pro-inflammatory mediators TNF-α, IL-1 (α and β), and NO, albeit at a variable rate and extent; 1,8-cineole diminished IL-1 and IL-6...
2017: PloS One
https://www.readbyqxmd.com/read/29128158/mitogen-activated-protein-kinase-regulation-in-hepatic-metabolism
#7
REVIEW
Ahmed Lawan, Anton M Bennett
The mitogen-activated protein kinases (MAPKs) participate in a multitude of processes that control hepatic metabolism. The liver regulates glucose and lipid metabolism, and under pathophysiological conditions such as obesity, type 2 diabetes mellitus (T2DM), and non-alcoholic fatty liver disease (NAFLD) these processes become dysfunctional. Stress responses activate the hepatic MAPKs, and this is thought to impair insulin action and lipid metabolism. The MAPKs also activate the MAPK phosphatases (MKPs) which oppose their actions...
November 8, 2017: Trends in Endocrinology and Metabolism: TEM
https://www.readbyqxmd.com/read/29109832/cardioprotective-effect-of-resveratrol-in-a-postinfarction-heart-failure-model
#8
Adam Riba, Laszlo Deres, Balazs Sumegi, Kalman Toth, Eszter Szabados, Robert Halmosi
Despite great advances in therapies observed during the last decades, heart failure (HF) remained a major health problem in western countries. In order to further improve symptoms and survival in patients with heart failure, novel therapeutic strategies are needed. In some animal models of HF resveratrol (RES), it was able to prevent cardiac hypertrophy, contractile dysfunction, and remodeling. Several molecular mechanisms are thought to be involved in its protective effects, such as inhibition of prohypertrophic signaling molecules, improvement of myocardial Ca(2+) handling, regulation of autophagy, and the reduction of oxidative stress and inflammation...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/29100381/dusp4-is-associated-with-increased-resistance-against-anti-her2-therapy-in-breast-cancer
#9
Otília Menyhart, Jan Budczies, Gyöngyi Munkácsy, Francisco J Esteva, András Szabó, Teresa Puig Miquel, Balázs Győrffy
The majority of patients develop resistance against suppression of HER2-signaling mediated by trastuzumab in HER2 positive breast cancer (BC). HER2 overexpression activates multiple signaling pathways, including the mitogen-activated protein kinase (MAPK) cascade. MAPK phosphatases (MKPs) are essential regulators of MAPKs and participate in many facets of cellular regulation, including proliferation and apoptosis. We aimed to identify whether differential MKPs are associated with resistance to targeted therapy in patients previously treated with trastuzumab...
September 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29077400/structural-and-dynamic-insights-into-the-mechanism-of-allosteric-signal-transmission-in-erk2-mediated-mkp3-activation
#10
Chang Lu, Xin Liu, Chen-Song Zhang, Haipeng Gong, Jia-Wei Wu, Zhi-Xin Wang
The mitogen-activated protein kinases (MAPKs) are key components of cellular signal transduction pathways, which are down-regulated by the MAPK phosphatases (MKPs). Catalytic activity of the MKPs is controlled both by their ability to recognize selective MAPKs and by allosteric activation upon binding to MAPK substrates. Here, we use a combination of experimental and computational techniques to elucidate the molecular mechanism for the ERK2-induced MKP3 activation. Mutational and kinetic study shows that the (334)FNFM(337) motif in the MKP3 catalytic domain is essential for MKP3-mediated ERK2 inactivation and is responsible for ERK2-mediated MKP3 activation...
November 8, 2017: Biochemistry
https://www.readbyqxmd.com/read/29067454/estradiol-postconditioning-relieves-ischemia-reperfusion-injury-in-axial-skin-flaps-of-rats-inhibits-apoptosis-and-alters-the-mkp-1-erk-pathway
#11
Qianheng Jin, Jihui Ju, Lei Xu, Yuefei Liu, Zhimin Li, Yi Fu, Ruixing Hou
Previous studies have suggested that estradiol can reduce the ischemia/reperfusion (I/R) injury in skin flaps. However, the mechanism, particularly the signal pathways involved in this protective effect are not well established. In the current study, an I/R injury model was established in rats to explore the connection between estradiol protection during I/R injury and extracellular signal‑regulated kinase (ERK) signaling. Healthy male Wistar rats were divided into five groups (n=10): Control group (group I), I/R group (group II), saline group (group III), estradiol group (group IV) and inhibitor (PD‑98059) group (group V)...
August 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29062272/obesity-increases-mitogen-activated-protein-kinase-phosphatase-3-levels-in-the-hypothalamus-of-mice
#12
Bárbara de A Rodrigues, Vitor R Muñoz, Gabriel K Kuga, Rafael C Gaspar, Susana C B R Nakandakari, Barbara M Crisol, José D Botezelli, Luciana S S Pauli, Adelino S R da Silva, Leandro P de Moura, Dennys E Cintra, Eduardo R Ropelle, José R Pauli
Mitogen-activated Protein Kinase Phosphatase 3 (MKP-3) has been involved in the negative regulation of insulin signaling. The absence of MKP-3 is also associated with reduced adiposity, increased energy expenditure and improved insulin sensitivity. The MKP-3 is known as the main Erk1/2 phosphatase and FoxO1 activator, which has repercussions on the gluconeogenesis pathway and hyperglycemia in obese mice. Recently, we showed that MKP-3 overexpression decreases FoxO1 phosphorylation in the hypothalamus of lean mice...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29052270/crystal-structure-of-the-human-dual-specificity-phosphatase-1-catalytic-domain
#13
Rajesh Gumpena, George T Lountos, Sreejith Raran-Kurussi, Joseph E Tropea, Scott Cherry, David S Waugh
The dual specificity phosphatase DUSP1 was the first mitogen activated protein kinase phosphatase (MKP) to be identified. It dephosphorylates conserved tyrosine and threonine residues in the activation loops of mitogen activated protein kinases ERK2, JNK1 and p38-alpha. Here, we report the crystal structure of the human DUSP1 catalytic domain at 2.49 Å resolution. Uniquely, the protein was crystallized as an MBP fusion protein in complex with a monobody that binds to MBP. Sulfate ions occupy the phosphotyrosine and putative phosphothreonine binding sites in the DUSP1 catalytic domain...
October 20, 2017: Protein Science: a Publication of the Protein Society
https://www.readbyqxmd.com/read/29047406/loss-of-mkp-5-promotes-myofiber-survival-by-activating-stat3-bcl-2-signaling-during-regenerative-myogenesis
#14
Kisuk Min, Ahmed Lawan, Anton M Bennett
BACKGROUND: The mitogen-activated protein kinases (MAPKs) have been shown to be involved in regulating myofiber survival. In skeletal muscle, p38 MAPK and JNK are negatively regulated by MAPK phosphatase-5 (MKP-5). During muscle regeneration, MKP-5 is downregulated, thereby promoting p38 MAPK/JNK signaling, and subsequent repair of damaged muscle. Mice lacking MKP-5 expression exhibit enhanced regenerative myogenesis. However, the effect of MKP-5 on myofiber survival during regeneration is unclear...
October 18, 2017: Skeletal Muscle
https://www.readbyqxmd.com/read/29041978/linc-ror-promotes-mapk-erk-signaling-and-confers-estrogen-independent-growth-of-breast-cancer
#15
Wan-Xin Peng, Jian-Guo Huang, Liu Yang, Ai-Hua Gong, Yin-Yuan Mo
BACKGROUND: The conversion from estrogen-dependent to estrogen-independent state of ER+ breast cancer cells is the key step to promote resistance to endocrine therapies. Although the crucial role of MAPK/ERK signaling pathway in estrogen-independent breast cancer cell growth is well established, the underlying mechanism is not fully understood. METHODS: In this study, we profiled lncRNA expression against a focused group of lncRNAs selected from lncRNA database...
October 17, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/28983247/microsomal-prostaglandin-e-synthase-1-expression-in-inflammatory-conditions-is-downregulated-by-dexamethasone-seminal-role-of-the-regulatory-phosphatase-mkp-1
#16
Lauri Tuure, Mari Hämäläinen, Brendan J Whittle, Eeva Moilanen
Microsomal prostaglandin E synthase-1 (mPGES-1) is an inducible enzyme situated downstream of cyclo-oxygenase-2, promoting the excessive PGE2 production in inflammation. Dexamethasone is known to suppress mPGES-1 but the mechanisms regulating mPGES-1 expression remain poorly known. MKP-1 is a phosphatase controlling the proinflammatory MAP kinase pathways p38 and JNK, thus limiting the inflammatory responses. We have now investigated the role of MKP-1 and MAP kinases p38 and JNK in the regulation of mPGES-1 expression by dexamethasone...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28974930/induction-of-mkp-1-and-nuclear-translocation-of-nrf2-by-limonoids-from-khaya-grandifoliola-c-dc-protect-l-02-hepatocytes-against-acetaminophen-induced-hepatotoxicity
#17
Arnaud F Kouam, Fei Yuan, Frédéric N Njayou, Hongtao He, Roméo F Tsayem, Babayemi O Oladejo, Fuhang Song, Paul F Moundipa, George F Gao
Drug-induced liver injury (DILI) is a major clinical problem where natural compounds hold promise for its abrogation. Khaya grandifoliola (Meliaceae) is used in Cameroonian traditional medicine for the treatment of liver related diseases and has been studied for its hepatoprotective properties. Till date, reports showing the hepatoprotective molecular mechanism of the plant are lacking. The aim of this study was therefore to identify compounds from the plant bearing hepatoprotective activity and the related molecular mechanism by assessing their effects against acetaminophen (APAP)-induced hepatotoxicity in normal human liver L-02 cells line...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28959039/mkp-1-negative-regulates-staphylococcus-aureus-induced-inflammatory-responses-in-raw264-7-cells-roles-of-pka-mkp-1-pathway-and-enhanced-by-rolipram
#18
Yiqing Pan, Chen Xu, Zhixing K Pan
MAP phosphatases (MKP)-1 acts as an important regulator of innate immune response through a mechanism of control and attention both MAPK and NF-κB molecules during bacterial infection. However, the regulatory role of MKP-1 in the interplay between MAPK and NFκB pathway molecules is still not fully understood. In present study, we showed a direct interactions of p38, ERK or IκBα with MKP-1, and demonstrated that MKP-1 was a pivotal feedback control for both MAP kinases and NF-κB pathway in response to S...
September 28, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28941781/glucocorticoids-and-toll-like-receptor-2-cooperatively-induce-acute-phase-serum-amyloid-a
#19
Qi Su, Günther Weindl
Serum amyloid A (SAA) is a highly conserved acute-phase protein and extrahepatic produced SAA1/2 contributes to cutaneous inflammation. Prolonged systemic or topical treatment with glucocorticoids can provoke skin diseases such as steroid-induced acne. Glucocorticoids increase Toll-like receptor 2 (TLR2) expression, however, an inflammatory mediator linked to this side effect remains elusive. We report that TLR2 agonists in combination with dexamethasone substantially increase SAA expression and production in human keratinocytes and epithelial cells...
September 20, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28904347/oscillatory-dynamics-of-p38-activity-with-transcriptional-and-translational-time-delays
#20
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
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