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https://www.readbyqxmd.com/read/28980048/protective-effects-of-the-resveratrol-analog-piceid-in-dopaminergic-sh-sy5y-cells
#1
Sneha Potdar, Mayur S Parmar, Sidhartha D Ray, Jane E Cavanaugh
Age-related motor deficits, such as loss of balance and coordination, are caused, in part, by loss of dopaminergic neurons. Oxidative stress is known to play a role in this neuronal loss. Resveratrol, a natural antioxidant with anticancer and anti-inflammatory potential, has been shown to protect dopaminergic-like cells (SH-SY5Y) against oxidative stress. However, the low bioavailability of resveratrol makes it worthwhile to explore newer compounds with similar properties. Piceid (RV8), an analog of resveratrol, has greater bioavailability than resveratrol, and our studies found that piceid (10, 20, 30 µM) protects SH-SY5Y cells against oxidative stress...
October 4, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28887535/metabolic-stress-induced-cardiomyopathy-is-caused-by-mitochondrial-dysfunction-due-to-attenuated-erk5-signaling
#2
Wei Liu, Andrea Ruiz-Velasco, Shoubao Wang, Saba Khan, Min Zi, Andreas Jungmann, Maria Dolores Camacho-Muñoz, Jing Guo, Guanhua Du, Liping Xie, Delvac Oceandy, Anna Nicolaou, Gina Galli, Oliver J Müller, Elizabeth J Cartwright, Yong Ji, Xin Wang
The prevalence of cardiomyopathy from metabolic stress has increased dramatically; however, its molecular mechanisms remain elusive. Here, we show that extracellular signal-regulated protein kinase 5 (Erk5) is lost in the hearts of obese/diabetic animal models and that cardiac-specific deletion of Erk5 in mice (Erk5-CKO) leads to dampened cardiac contractility and mitochondrial abnormalities with repressed fuel oxidation and oxidative damage upon high fat diet (HFD). Erk5 regulation of peroxisome proliferator-activated receptor γ co-activator-1α (Pgc-1α) is critical for cardiac mitochondrial functions...
September 8, 2017: Nature Communications
https://www.readbyqxmd.com/read/28878225/the-pdk1-inhibitor-dichloroacetate-controls-cholesterol-homeostasis-through-the-erk5-mef2-pathway
#3
Abrar Ul Haq Khan, Nerea Allende-Vega, Delphine Gitenay, Sabine Gerbal-Chaloin, Claire Gondeau, Dang-Nghiem Vo, Sana Belkahla, Stefania Orecchioni, Giovanna Talarico, Francesco Bertolini, Milica Bozic, Jose M Valdivielso, Fabienne Bejjani, Isabelle Jariel, Isabel C Lopez-Mejia, Lluis Fajas, Charles-Henri Lecellier, Javier Hernandez, Martine Daujat, Martin Villalba
Controlling cholesterol levels is a major challenge in human health, since hypercholesterolemia can lead to serious cardiovascular disease. Drugs that target carbohydrate metabolism can also modify lipid metabolism and hence cholesterol plasma levels. In this sense, dichloroacetate (DCA), a pyruvate dehydrogenase kinase (PDK) inhibitor, augments usage of the glycolysis-produced pyruvate in the mitochondria increasing oxidative phosphorylation (OXPHOS). In several animal models, DCA decreases plasma cholesterol and triglycerides...
September 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28835924/vomocytosis-of-live-pathogens-from-macrophages-is-regulated-by-the-atypical-map-kinase-erk5
#4
Andrew S Gilbert, Paula I Seoane, Poppy Sephton-Clark, Aleksandra Bojarczuk, Richard Hotham, Emanuele Giurisato, Adil R Sarhan, Amy Hillen, Greetje Vande Velde, Nathanael S Gray, Dario R Alessi, Debbie L Cunningham, Cathy Tournier, Simon A Johnston, Robin C May
Vomocytosis, or nonlytic extrusion, is a poorly understood process through which macrophages release live pathogens that they have failed to kill back into the extracellular environment. Vomocytosis is conserved across vertebrates and occurs with a diverse range of pathogens, but to date, the host signaling events that underpin expulsion remain entirely unknown. We use a targeted inhibitor screen to identify the MAP kinase ERK5 as a critical suppressor of vomocytosis. Pharmacological inhibition or genetic manipulation of ERK5 activity significantly raises vomocytosis rates in human macrophages, whereas stimulation of the ERK5 signaling pathway inhibits vomocytosis...
August 2017: Science Advances
https://www.readbyqxmd.com/read/28751752/tannic-acid-as-a-plant-derived-polyphenol-exerts-vasoprotection-via-enhancing-klf2-expression-in-endothelial-cells
#5
Yanni Xu, Peng Liu, Suowen Xu, Marina Koroleva, Shuya Zhang, Shuyi Si, Zheng Gen Jin
The transcription factor Kruppel-like factor 2 (KLF2) is a critical anti-inflammatory and anti-atherogenic molecule in vascular endothelium. Enhancing KLF2 expression and activity improves endothelial function and prevents atherosclerosis. However, the pharmacological and molecular regulators for KLF2 are scarce. Using high-throughput luciferase reporter assay to screen for KLF2 activators, we have identified tannic acid (TA), a polyphenolic compound, as a potent KLF2 activator that attenuates endothelial inflammation...
July 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28746466/microrna-143-inhibits-cell-growth-by-targeting-erk5-and-map3k7-in-breast-cancer
#6
L L Zhou, J L Dong, G Huang, Z L Sun, J Wu
This study aimed to investigate the function and mechanism of microRNA-143 (miR-143) in the occurrence and development of breast cancer (BC). A total of 30 BC tissues, 30 corresponding noncancerous tissues, and 10 normal control (NC) breast tissues were obtained to detect the levels of miR-143, extracellular signal-regulated kinase 5 (ERK5) and mitogen-activated protein 3 kinase 7 (MAP3K7) using RT-qPCR, western blotting or immunohistochemistry. The correlation of miR-143 with ERK5 or MAP3K7 was evaluated using Pearson correlation analysis...
July 20, 2017: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
https://www.readbyqxmd.com/read/28681594/chop-deficiency-ameliorates-erk5-inhibition-mediated-exacerbation-of-streptozotocin-induced-hyperglycemia-and-pancreatic-%C3%AE-cell-apoptosis
#7
Dae-Hwan Nam, Jung-Hwa Han, Jae Hyang Lim, Kwon Moo Park, Chang-Hoon Woo
Streptozotocin (STZ)-induced murine models of type 1 diabetes have been used to examine ER stress during pancreatic β-cell apoptosis, as this ER stress plays important roles in the pathogenesis and development of the disease. However, the mechanisms linking type 1 diabetes to the ER stress-modulating anti-diabetic signaling pathway remain to be addressed, though it was recently established that ERK5 (Extracellular-signal-regulated kinase 5) contributes to the pathogeneses of diabetic complications. This study was undertaken to explore the mechanism whereby ERK5 inhibition instigates pancreatic β-cell apoptosis via an ER stress-dependent signaling pathway...
July 31, 2017: Molecules and Cells
https://www.readbyqxmd.com/read/28675952/a-novel-fine-tuning-scheme-of-mir-200c-in-modulating-lung-cell-redox-homeostasis
#8
Yi-Hsuan Wu, Hsin-Ru Lin, Ying-Hsuan Lee, Pin-Hao Huang, Huei-Chung Wei, Arnold Stern, Daniel Tsun-Yee Chiu
Oxidative stress induces miR-200c, the predominant microRNA (miRNA) in lung tissues; however, the antioxidant role and biochemistry of such induction have not been clearly defined. Therefore, a lung adenocarcinoma cell line (A549) and a normal lung fibroblast (MRC-5) were used as models to determine the effects of miR-200c expression on lung antioxidant response. Hydrogen peroxide (H2O2) upregulated miR-200c, whose overexpression exacerbated the decrease in cell proliferation, retarded the progression of cells in the G2/M-phase, and increased oxidative stress upon H2O2 stimulation...
July 4, 2017: Free Radical Research
https://www.readbyqxmd.com/read/28669729/mangiferin-protects-osteoblast-against-oxidative-damage-by-modulation-of-erk5-nrf2-signaling
#9
Gen Xia, Xueru Li, Xi Zhu, Xueming Yin, Huiqiang Ding, Yongdong Qiao
Oxidative stress has currently been proposed as a risk factor associated with the development and proression of osteoporosis. In this study, we identify the effect of mangiferin (MAN) on apoptosis and differentiation of osteoblast-like MC3T3-E1 cells insulted by H2O2. We firstly found that MAN can promote cell proliferation of MC3T3-E1 cells in a time- and dose-dependent manner and stimulate the phosphorylation of ERK5. Cells were divided as five groups: control, H2O2 (100 μM, control), H2O2 + MAN (5 μM), H2O2 + MAN (10 μM), and H2O2 + MAN (20 μM)...
September 23, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28662520/regulation-of-ap-1-by-mapk-signaling-in-metal-stressed-sea-anemone
#10
Maayan Agron, Vera Brekhman, David Morgenstern, Tamar Lotan
BACKGROUND/AIMS: AP-1 transcription factor plays a conserved role in the immediate response to stress. Activation of AP-1 members jun and fos is mediated by complex signaling cascades to control cell proliferation and survival. To understand the evolution of this broadly-shared pathway, we studied AP-1 regulation by MAPK signaling in a basal metazoan. METHODS: Metal- stressed cnidarian Nematostella vectensis anemones were tested with kinase inhibitors and analyzed for gene expression levels and protein phosphorylation...
June 27, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28639275/statin-regulated-erk5-stimulates-tight-junction-formation-and-reduces-permeability-in-human-cardiac-endothelial-cells
#11
Emma L Wilkinson, James E Sidaway, Michael J Cross
The MEKK3/MEK5/ERK5 signaling axis is required for cardiovascular development in vivo. We analyzed the physiological role of ERK5 in cardiac endothelial cells and the consequence of activation of this kinase by the statin class of HMG Co-A reductase inhibitor drugs. We utilized human cardiac microvascular endothelial cells (HCMECs) and altered ERK5 expression using siRNA mediated gene silencing or overexpression of constitutively active MEK5 and ERK5 to reveal a role for ERK5 in regulating endothelial tight junction formation and cell permeability...
January 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28630262/dipeptidyl-peptidase-4-inhibitor-anagliptin-prevents-intracranial-aneurysm-growth-by-suppressing-macrophage-infiltration-and-activation
#12
Taichi Ikedo, Manabu Minami, Hiroharu Kataoka, Kosuke Hayashi, Manabu Nagata, Risako Fujikawa, Sei Higuchi, Mika Yasui, Tomohiro Aoki, Miyuki Fukuda, Masayuki Yokode, Susumu Miyamoto
BACKGROUND: Chronic inflammation plays a key role in the pathogenesis of intracranial aneurysms (IAs). DPP-4 (dipeptidyl peptidase-4) inhibitors have anti-inflammatory effects, including suppressing macrophage infiltration, in various inflammatory models. We examined whether a DPP-4 inhibitor, anagliptin, could suppress the growth of IAs in a rodent aneurysm model. METHODS AND RESULTS: IAs were surgically induced in 7-week-old male Sprague Dawley rats, followed by oral administration of 300 mg/kg anagliptin...
June 19, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28626076/cardiac-fibroblast-transcriptome-analyses-support-a-role-for-interferogenic-profibrotic-and-inflammatory-genes-in-anti-ssa-ro-associated-congenital-heart-block
#13
Robert M Clancy, Androo J Markham, Tanisha Jackson, Sara E Rasmussen, Miroslav Blumenberg, Jill P Buyon
The signature lesion of SSA/Ro autoantibody-associated congenital heart block (CHB) is fibrosis and a macrophage infiltrate, supporting an experimental focus on cues influencing the fibroblast component. The transcriptomes of human fetal cardiac fibroblasts were analyzed using two complementary approaches. Cardiac injury conditions were simulated in vitro by incubating human fetal cardiac fibroblasts with supernatants from macrophages transfected with the SSA/Ro-associated noncoding Y ssRNA. The top 10 upregulated transcripts in the stimulated fibroblasts reflected a type I interferon (IFN) response [e...
September 1, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28624320/prognostic-value-of-the-vhl-hif-1%C3%AE-and-vegf-signaling-pathway-and-associated-mapk-erk1-2-and-erk5-pathways-in-clear-cell-renal-cell-carcinoma-a-long-term-study
#14
Antonio S Salinas-Sánchez, Leticia Serrano-Oviedo, Syongh Y Nam-Cha, Olga Roche-Losada, Ricardo Sánchez-Prieto, José M Giménez-Bachs
BACKGROUND: The prognostic value of molecular markers in renal cell carcinoma has been investigated in several studies. Although their value is still not confirmed, various proteins are important. We describe the effect on long-term survival of the status of the von Hippel-Lindau (VHL) hypoxia-inducible factor 1-α (HIF1-α) signaling pathway as well as associated mitogen-activated protein kinase (extracellular signal-regulated kinase [ERK]1/2 and ERK5). PATIENTS AND METHODS: A prospective, longitudinal cohort study was conducted with 50 patients diagnosed with clear-cell renal cell carcinoma to analyze VHL mutations and hypermethylation as well as VHL, HIF1-α, vascular endothelial growth factor (VEGF), ERK1/2, and ERK5 protein expression...
May 25, 2017: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/28603902/extracellular-signal-regulated-kinase-5-associates-with-casein-kinase-ii-to-regulate-gpib-ix-mediated-platelet-activation-via-the-pten-pi3k-akt-pathway
#15
Z Cheng, W Gao, X Fan, X Chen, H Mei, J Liu, X Luo, Y Hu
Essentials The mechanisms of extracellular signal-regulated kinase 5 (ERK5) in GPIb-IX signaling are unclear. Function of ERK5 in GPIb-IX was tested using aggregation, western blotting, and mass spectrometry. The protein interacting with ERK5 in human platelets was identified as casein kinase II (CKII). ERK5 associates with CKII to regulate the activation of the PI3K/Akt pathway in GPIb-IX signaling. SUMMARY: Background The platelet glycoprotein (GP) Ib-IX complex plays essential roles in thrombosis and hemostasis...
June 11, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28592707/endothelial-nitric-oxide-synthase-independent-pleiotropic-effects-of-pitavastatin-against-atherogenesis-and-limb-ischemia-in-mice
#16
Takeshi Mitsuhashi, Ryoko Uemoto, Kazue Ishikawa, Sumiko Yoshida, Yasumasa Ikeda, Shusuke Yagi, Toshio Matsumoto, Masashi Akaike, Ken-Ichi Aihara
AIM: Statins have a protective impact against cardiovascular diseases through not only lipid-lowering effects but also pleiotropic effects, including activation of the endothelial nitric oxide synthase (eNOS) system. We aimed to clarify the protective effects of a statin against atherogenesis and ischemia in eNOS(-/-) mice. METHODS: Study 1. eNOS(-/-) Apolipoprotein E (ApoE)(-/-) mice were treated with a vehicle or pitavastatin (0.3 mg/kg/day) for 4 weeks...
June 6, 2017: Journal of Atherosclerosis and Thrombosis
https://www.readbyqxmd.com/read/28585748/effects-of-curcumin-on-tobacco-smoke-induced-hepatic-mapk-pathway-activation-and-epithelial-mesenchymal-transition-in-vivo
#17
Zhaofeng Liang, Rui Wu, Wei Xie, Chunfeng Xie, Jieshu Wu, Shanshan Geng, Xiaoting Li, Mingming Zhu, Weiwei Zhu, Jianyun Zhu, Cong Huang, Xiao Ma, Wenrong Xu, Caiyun Zhong, Hongyu Han
Tobacco smoke is a major risk factor for hepatic cancer. Epithelial-mesenchymal transition (EMT) induced by tobacco smoke is crucially involved in the initiation and development of cancer. Mitogen-activated protein kinase (MAPK) pathways play important roles in tobacco smoke-associated carcinogenesis including EMT process. The chemopreventive effect of curcumin supplementation against cancers has been reported. In this study, we investigated the effects of tobacco smoke on MAPK pathway activation and EMT alterations, and then the preventive effect of curcumin was examined in the liver of BALB/c mice...
August 2017: Phytotherapy Research: PTR
https://www.readbyqxmd.com/read/28566937/shear-stress-induces-change-in-extracellular-signal-regulated-kinase-5-levels-with-sustained-activation-under-disturbed-and-continuous-laminar-flow
#18
S Y Shalaby, G Chitragari, B J Sumpio, B E Sumpio
Extracellular signal-regulated kinase 5 (ERK5) has been reported to regulate endothelial integrity and protect from vascular dysfunction under laminar flow. Previously reported research indicates that under laminar flow ERK5 is activated with production of atheroprotective molecules. However, the characterization of ERK5 activation and levels under different flow patterns has not been investigated. Confluent HUVECs were serum-starved then seeded on glass slides. HUVECs incubated in 1% FBS were exposed to continuous laminar flow (CLF), to-and-fro flow (TFF), or pulsatile forward flow (PFF) in a parallel plate flow chamber...
June 2017: International Journal of Angiology: Official Publication of the International College of Angiology, Inc
https://www.readbyqxmd.com/read/28560410/dclk1-is-correlated-with-met-and-erk5-expression-and-associated-with-prognosis-in-malignant-pleural-mesothelioma
#19
Hui Wang, Yu-Yuan Dai, Wen-Qian Zhang, Ping-Chih Hsu, Yi-Lin Yang, Yu-Cheng Wang, Geraldine Chan, Alfred Au, Zhi-Dong Xu, Shu-Juan Jiang, Wei Wang, David M Jablons, Liang You
Malignant pleural mesothelioma (MPM) is an aggressive cancer for which more effective treatments are needed. In this study, strong to moderate staining of MET and ERK5 was detected in 67.1 and 48% of the analyzed 73 human mesothelioma tumors, and significant correlation of MET and ERK5 expression was identified (P<0.05). We evaluated the doublecortin-like kinase 1 (DCLK1) expression in human mesothelioma tumors. Our results showed that 50.7% of the immunohistochemistry analyzed human mesothelioma tumors have strong to moderate staining of DCLK1, and its expression is significantly correlated with MET or ERK5 expression (P<0...
July 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28542559/fluvastatin-inhibits-age-induced-cell-proliferation-and-migration-via-an-erk5-dependent-nrf2-pathway-in-vascular-smooth-muscle-cells
#20
Ae-Rang Hwang, Jung-Hwa Han, Jae Hyang Lim, Young Jin Kang, Chang-Hoon Woo
Advanced glycation endproduct (AGE)-induced vascular smooth muscle cell (VSMC) proliferation and reactive oxygen species (ROS) production are emerging as important mechanisms of diabetic vasculopathy, but little is known about the molecular mechanism responsible for the antioxidative effects of statins on AGEs. It has been reported that statins exert pleiotropic effects on the cardiovascular system due to decreases in AGE-induced cell proliferation, migration, and vascular inflammation. Thus, in the present study, the authors investigated the molecular mechanism by which statins decrease AGE-induced cell proliferation and VSMC migration...
2017: PloS One
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