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https://www.readbyqxmd.com/read/29221196/identification-of-cellular-genes-and-pathways-important-for-tumorigenicity-of-hepatocellular-carcinoma-cell-lines-by-proteomic-profiling
#1
Ali Zamani, Huahao Fan, Guangxiang Luo
Hepatocellular carcinoma (HCC) is the most commonly diagnosed malignancy of the liver. A more thorough understanding of HCC pathogenesis will provide novel targets for development of cancer drugs to effectively treat HCC. To further this goal, we carried out a proteomic profiling of HCC cell lines Huh-7.4 and Huh-7.5. These two cell lines were derived from subgenomic HCV RNA-replicating Huh-7 cells upon clearance of HCV RNA by antiviral drug treatment. Initially, the tumorigenicity of each cell line was determined and compared in parallel in the same immunedeficient mice...
November 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29184034/mek-inhibitor-trametinib-does-not-prevent-the-growth-of-anaplastic-lymphoma-kinase-alk-addicted-neuroblastomas
#2
Ganesh Umapathy, Jikui Guan, Dan E Gustafsson, Niloufar Javanmardi, Diana Cervantes-Madrid, Anna Djos, Tommy Martinsson, Ruth H Palmer, Bengt Hallberg
Activation of the RAS-RAF-MEK-ERK signaling pathway is implicated in driving the initiation and progression of multiple cancers. Several inhibitors targeting the RAS-MAPK pathway are clinically approved as single- or polyagent therapies for patients with specific types of cancer. One example is the MEK inhibitor trametinib, which is included as a rational polytherapy strategy for treating EML4-ALK-positive, EGFR-activated, or KRAS-mutant lung cancers and neuroblastomas that also contain activating mutations in the RAS-MAPK pathway...
November 28, 2017: Science Signaling
https://www.readbyqxmd.com/read/29159830/erk5-plays-an-essential-role-in-gestational-beta-cell-proliferation
#3
Congde Chen, Suichun Wu, Xiaokun Lin, Dazhou Wu, Shane Fischbach, Xiangwei Xiao
OBJECTIVES: Restoring a functional beta-cell mass is a fundamental goal in treating diabetes. A complex signalling pathway network coordinates the regulation of beta-cell proliferation, although a role for ERK5 in this network has not been reported. This question was addressed in this study. MATERIALS AND METHODS: We studied the activation of extracellular-signal-regulated kinase 5 (ERK5) in pregnant mice, a well-known mouse model of increased beta-cell proliferation...
November 21, 2017: Cell Proliferation
https://www.readbyqxmd.com/read/29149682/signalling-for-b-cell-survival
#4
REVIEW
Edina Schweighoffer, Victor Lj Tybulewicz
The number of mature B cells is carefully controlled by signalling from receptors that support B cell survival. The best studied of these are the B cell antigen receptor (BCR) and BAFFR. Recent work has shown that signalling from these receptors is closely linked, involves the CD19 co-receptor, and leads to activation of canonical and non-canonical NF-κB pathways, ERK1, ERK2 and ERK5 MAP kinases, and PI-3 kinases. Importantly, studies show that investigation of the importance of signalling molecules in cell survival requires the use of inducible gene deletions within mature B cells...
November 14, 2017: Current Opinion in Cell Biology
https://www.readbyqxmd.com/read/29138815/curcumin-reverses-tobacco-smoke%C3%A2-induced-epithelial%C3%A2-mesenchymal-transition-by-suppressing-the-mapk-pathway-in-the-lungs-of-mice
#5
Zhaofeng Liang, Rui Wu, Wei Xie, Mingming Zhu, Chunfeng Xie, Xiaoting Li, Jianyun Zhu, Weiwei Zhu, Jieshu Wu, Shanshan Geng, Wenrong Xu, Caiyun Zhong, Hongyu Han
Tobacco smoke is a major risk factor for lung cancer. Epithelial‑mesenchymal transition (EMT) is decisive in cancer invasion and metastasis, and therefore promotes cancer progression. Mitogen‑activated protein kinase (MAPK) pathways are implicated in various aspects of cancer development and progression, including the EMT process. The chemopreventive effect of curcumin on carcinogenesis has been reported in vivo and in vitro. The present study investigated tobacco smoke‑induced alterations in the MAPK/activator protein‑1 (AP‑1) pathways, and pulmonary EMT changes in the lungs of mice, and further observed the chemopreventive effect of curcumin...
November 13, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29127222/mef2-transcription-factors-in-human-placenta-and-involvement-in-cytotrophoblast-invasion-and-differentiation
#6
Lucy Li, Lewis P Rubin, Xiaoming Gong
Development of the human placenta and its trophoblast cell types is critical for successful pregnancy. Defects in trophoblast invasion and differentiation are associated with adverse pregnancy outcomes, including preeclampsia. The members of myocyte enhancer factor-2 (MEF2) family of transcription factors are key regulators of cellular proliferation, differentiation, and invasion in various cell types and tissues and might play a similarly important role in regulating trophoblast proliferation, invasion, and differentiation during human placental development...
November 10, 2017: Physiological Genomics
https://www.readbyqxmd.com/read/29096169/lunasin-abrogates-monocytes-to-endothelial-cells
#7
Yongjun Zhu, Hui Li, Xuezhen Wang
The adherence of monocytes to endothelial cells plays a causal role in the early development of atherosclerosis and is driven by several inflammatory stimuli, which includes oxidized low-density lipoprotein (ox-LDL). Lunasin, a natural peptide identified in soybean seeds, soy-derived food products, other grains and herbal plants, has been found to exert numerous biological activities, including anti-inflammatory and antioxidant properties. However, little is known regarding the mechanism of action of lunasin in ox-LDL-induced endothelial inflammation...
October 30, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/29038439/analysis-of-nkx3-1-cre-driven-erk5-deletion-reveals-a-profound-spinal-deformity-which-is-linked-to-increased-osteoclast-activity
#8
Carolyn J Loveridge, Rob J van 't Hof, Gemma Charlesworth, Ayala King, Ee Hong Tan, Lorraine Rose, Anna Daroszewska, Amanda Prior, Imran Ahmad, Michelle Welsh, Ernest J Mui, Catriona Ford, Mark Salji, Owen Sansom, Karen Blyth, Hing Y Leung
Extracellular signal-regulated protein kinase 5 (ERK5) has been implicated during development and carcinogenesis. Nkx3.1-mediated Cre expression is a useful strategy to genetically manipulate the mouse prostate. While grossly normal at birth, we observed an unexpected phenotype of spinal protrusion in Nkx3.1:Cre;Erk5 (fl/fl) (Erk5 (fl/fl)) mice by ~6-8 weeks of age. X-ray, histological and micro CT (µCT) analyses showed that 100% of male and female Erk5 (fl/fl) mice had a severely deformed curved thoracic spine, with an associated loss of trabecular bone volume...
October 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28980048/protective-effects-of-the-resveratrol-analog-piceid-in-dopaminergic-sh-sy5y-cells
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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...
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
#19
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
#20
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
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