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https://www.readbyqxmd.com/read/29609502/fluid-shear-stress-promotes-osteoblast-proliferation-through-the-nfatc1-erk5-pathway
#1
Ning Ding, Bin Geng, Zhonghao Li, Quanzeng Yang, Liang Yan, Lang Wan, Bo Zhang, Cuifang Wang, Yayi Xia
PURPOSE: Extracellular signal regulated kinase 5 (ERK5) is thought to regulate osteoblast proliferation. To further understand how ERK5 signalling regulates osteoblast proliferation induced by fluid shear stress (FSS), we examined some potential signalling targets associated with ERK5 in MC3T3-E1 cells. METHODS: MC3T3-E1 cells were treated with XMD8-92 (an ERK5 inhibitor) or Cyclosporin A (CsA, a Nuclear Factor of Activated T Cells (NFAT) c1 inhibitor) and/or exposed to 12 dyn/cm2 FSS...
April 3, 2018: Connective Tissue Research
https://www.readbyqxmd.com/read/29594152/ionizing-radiation-induces-endothelial-inflammation-and-apoptosis-via-p90rsk-mediated-erk5-s496-phosphorylation
#2
Hang Thi Vu, Sivareddy Kotla, Kyung Ae Ko, Yuka Fujii, Yunting Tao, Jan Medina, Tamlyn Thomas, Megumi Hada, Anil K Sood, Pankaj Kumar Singh, Sarah A Milgrom, Sunil Krishnan, Keigi Fujiwara, Nhat-Tu Le, Jun-Ichi Abe
Adverse cardiovascular events are a leading nonmalignant cause of morbidity and mortality among cancer survivors who have been exposed to ionizing radiation (IR), but the exact mechanism of the cardiovascular complications induced by IR remains unclear. In this study we investigated the potential role of the p90RSK-ERK5 module in regulating IR-induced endothelial cell inflammation and apoptosis. Whole body radiation of mice with 2 Gy γ-ray significantly increased endothelial VCAM-1 expression; especially in the disturbed flow area in vivo ...
2018: Frontiers in Cardiovascular Medicine
https://www.readbyqxmd.com/read/29577856/blood-flow-regulates-zebrafish-caudal-vein-plexus-angiogenesis-by-erk5-klf2a-nos2b-signaling
#3
X Xie, T Zhou, Y Wang, H Chen, D Lei, L Huang, Y Wang, X Jin, T Sun, J Tan, T Yin, J Huang, H Gregersen, G Wang
Vascular network formation induced by angiogenesis plays an important role in many physiological and pathological processes. However, the role of blood flow and underlying mechanisms in vascular network formation, for example for the development of the caudal vein plexus (CVP), is poorly understood. In this study on tnnt2a-MO injection and chemical blood flow modulator treatment in zebrafish embryos, we demonstrated that decreased blood flow disrupted CVP formation. The hemodynamic force was quantitatively analyzed...
March 22, 2018: Current Molecular Medicine
https://www.readbyqxmd.com/read/29568918/protection-of-luteolin-7-o-glucoside-against-apoptosis-induced-by-hypoxia-reoxygenation-through-the-mapk-pathways-in-h9c2-cells
#4
Shenjie Chen, Bingsheng Yang, Yifei Xu, Yiqing Rong, Yuangang Qiu
Myocardial hypertrophy is often associated with myocardial infarction. Luteolin-7-O-glucoside (LUTG) has the prosperity of preventing cardiomyocyte injury. The current study aimed to explore the potential protective effect of LUTG and its relevant mechanisms in the heart. To establish the cardiac hypertrophy model in vitro, Angiotensin II (Ang II) was used to stimuli H9c2 cells in this study. The CCK‑8 assay showed that LUTG pretreatment improved cell viability of cardiomyocytes co‑treated with Ang II and ischemia/reperfusion...
March 19, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29567200/the-mek5-erk5-mitogen-activated-protein-kinase-cascade-is-an-effector-pathway-of-bone-sustaining-bisphosphonates-that-regulates-osteogenic-differentiation-and-mineralization
#5
Christian Adam, Lucia Glück, Regina Ebert, Matthias Goebeler, Franz Jakob, Marc Schmidt
Bisphosphonates play an important role in the treatment of metabolic bone diseases such as osteoporosis. In addition to their anti-resorptive activity by triggering osteoclast apoptosis, nitrogen-containing bisphosphonates (N-BP) may also influence osteogenic differentiation, which might rely on their capacity to inhibit the mevalonate pathway. In vascular endothelial cells inhibition of this pathway by cholesterol-lowering statins activates the MEK5/ERK5 mitogen-activated protein kinase cascade, which plays an important role in cellular differentiation, apoptosis or inflammatory processes...
March 19, 2018: Bone
https://www.readbyqxmd.com/read/29542225/memantine-protects-against-ischemia-reperfusion-induced-brain-endothelial-permeability
#6
Yingying Liu, Yudiao Huang, Yueyue Xu, Peng Qu, Minghua Wang
Increased transendothelial permeability and subsequent blood-brain barrier damage play a key role in the pathological progression of human brain ischemia and secondary reperfusion. Memantine is a licensed drug providing clinically relevant efficacy in patients with Alzheimer's disease. However, little information is known regarding its effects on brain endothelial permeability. In this study, we investigated the effects of memantine on endothelial permeability and the underlying mechanisms in an ischemia-reperfusion (I/R) injury model in primary human brain microvascular endothelial cells...
March 15, 2018: IUBMB Life
https://www.readbyqxmd.com/read/29511711/data-in-support-of-sustained-upregulation-of-adaptive-redox-homeostasis-mechanisms-caused-by-krit1-loss-of-function
#7
Cinzia Antognelli, Eliana Trapani, Simona Delle Monache, Andrea Perrelli, Claudia Fornelli, Francesca Retta, Paola Cassoni, Vincenzo Nicola Talesa, Saverio Francesco Retta
This article contains additional data related to the original research article entitled "KRIT1 loss-of-function induces a chronic Nrf2-mediated adaptive homeostasis that sensitizes cells to oxidative stress: implication for Cerebral Cavernous Malformation disease" (Antognelli et al., 2017) [1]. Data were obtained by si-RNA-mediated gene silencing, qRT-PCR, immunoblotting, and immunohistochemistry studies, and enzymatic activity and apoptosis assays. Overall, they support, complement and extend original findings demonstrating that KRIT1 loss-of-function induces a redox-sensitive and JNK-dependent sustained upregulation of the master Nrf2 antioxidant defense pathway and its downstream target Glyoxalase 1 (Glo1), and a drop in intracellular levels of AP-modified Hsp70 and Hsp27 proteins, leading to a chronic adaptive redox homeostasis that sensitizes cells to oxidative DNA damage and apoptosis...
February 2018: Data in Brief
https://www.readbyqxmd.com/read/29507229/myeloid-erk5-deficiency-suppresses-tumor-growth-by-blocking-protumor-macrophage-polarization-via-stat3-inhibition
#8
Emanuele Giurisato, Qiuping Xu, Silvia Lonardi, Brian Telfer, Ilaria Russo, Adam Pearson, Katherine G Finegan, Wenbin Wang, Jinhua Wang, Nathanael S Gray, William Vermi, Zhengui Xia, Cathy Tournier
Owing to the prevalence of tumor-associated macrophages (TAMs) in cancer and their unique influence upon disease progression and malignancy, macrophage-targeted interventions have attracted notable attention in cancer immunotherapy. However, tractable targets to reduce TAM activities remain very few and far between because the signaling mechanisms underpinning protumor macrophage phenotypes are largely unknown. Here, we have investigated the role of the extracellular-regulated protein kinase 5 (ERK5) as a determinant of macrophage polarity...
March 5, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29483645/erk5-is-activated-by-oncogenic-braf-and-promotes-melanoma-growth
#9
Ignazia Tusa, Sinforosa Gagliardi, Alessandro Tubita, Silvia Pandolfi, Carmelo Urso, Lorenzo Borgognoni, Jinhua Wang, Xianming Deng, Nathanael S Gray, Barbara Stecca, Elisabetta Rovida
Malignant melanoma is among the most aggressive cancers and its incidence is increasing worldwide. Targeted therapies and immunotherapy have improved the survival of patients with metastatic melanoma in the last few years; however, available treatments are still unsatisfactory. While the role of the BRAF-MEK1/2-ERK1/2 pathway in melanoma is well established, the involvement of mitogen-activated protein kinases MEK5-ERK5 remains poorly explored. Here we investigated the function of ERK5 signaling in melanoma...
February 27, 2018: Oncogene
https://www.readbyqxmd.com/read/29467254/bdnf-activates-an-nfi-dependent-neurodevelopmental-timing-program-by-sequestering-nfatc4
#10
Baojin Ding, Paul R Dobner, Debra Mullikin-Kilpatrick, Wei Wang, Hong Zhu, Chi-Wing Chow, John W Cave, Richard M Gronostajski, Daniel L Kilpatrick
How intrinsic and extrinsic signals are coordinated to regulate synaptic maturation and its timing is an important question for neurodevelopment and its disorders. Here, we investigated the influence of the neurotrophin BDNF on the developmental timing of a dendrite/synapse-related gene program controlled by Nuclear Factor One (NFI) in maturing cerebellar granule neurons (CGNs). BDNF accelerated the onset of NFI-regulated late-gene expression and NFI temporal occupancy in CGN cultures in a MEK5/ERK5-dependent manner...
February 21, 2018: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/29463068/benzidine-induces-epithelial-mesenchymal-transition-of-human-bladder-cancer-cells-through-activation-of-erk5-pathway
#11
Xin Sun, Tao Zhang, Qifei Deng, Qirui Zhou, Xianchao Sun, Enlai Li, Dexin Yu, Caiyun Zhong
Benzidine, a known carcinogen, is closely associated with the development of bladder cancer (BC). Epithelial-mesenchymal transition (EMT) is a critical pathophysiological process in BC progression. The underlying molecular mechanisms of mitogen-activated protein kinase (MAPK) pathway, especially extracellular regulated protein kinases 5 (ERK5), in regulating benzidine-induced EMT remains unclarified. Hence, two human bladder cell lines, T24 and EJ, were utilized in our study. Briefly, cell migration was assessed by wound healing assay, and cell invasion was determined by Transwell assay...
February 21, 2018: Molecules and Cells
https://www.readbyqxmd.com/read/29416689/molecular-regulation-of-erk5-in-development-of-diabetic-retinopathy
#12
Qi Zhao, Lin Wang, Yuan Sun, Xiao-Xia Wang
Diabetic retinopathy (DR) is a major complication of diabetes, and causes pathological changes in retina blood vessels, as the most common cause of vision loss. Extracellular-signal-regulated kinase 5 (ERK5) is the newest discovered member in the mitogen-activated protein kinases (MAPKs) family, and recent evidence demonstrates an essential role of ERK5 signaling in the angiogenesis. However, whether ERK5 signaling may regulate DR development is unknown. Here, we used a streptozocin (STZ)-induce mouse DR model to investigate this question...
January 2, 2018: Oncotarget
https://www.readbyqxmd.com/read/29416681/changes-in-metabolism-affect-expression-of-abc-transporters-through-erk5-and-depending-on-p53-status
#13
Sana Belkahla, Abrar Ul Haq Khan, Delphine Gitenay, Catherine Alexia, Claire Gondeau, Dang-Nghiem Vo, Stefania Orecchioni, Giovanna Talarico, Francesco Bertolini, Guillaume Cartron, Javier Hernandez, Martine Daujat-Chavanieu, Nerea Allende-Vega, Martin Villalba Gonzalez
Changes in metabolism require the efflux and influx of a diverse variety of metabolites. The ABC superfamily of transporters regulates the exchange of hundreds of substrates through the impermeable cell membrane. We show here that a metabolic switch to oxidative phosphorylation (OXPHOS), either by treating cells with dichloroacetate (DCA) or by changing the available substrates, reduced expression of ABCB1, ABCC1, ABCC5 and ABCG2 in wild-type p53-expressing cells. This metabolic change reduced histone changes associated to active promoters...
January 2, 2018: Oncotarget
https://www.readbyqxmd.com/read/29416614/extracellular-signal-regulated-kinase-5-and-inflammasome-in-progression-of-mesothelioma
#14
Joyce K Thompson, Anurag Shukla, Alan L Leggett, Phillip B Munson, Jill M Miller, Maximilian B MacPherson, Stacie L Beuschel, Harvey I Pass, Arti Shukla
Malignant mesothelioma is an aggressive cancer in desperate need of treatment. We have previously shown that extracellular signaling regulated kinase 5 (ERK5) plays an important role in mesothelioma pathogenesis using ERK5 silenced human mesothelioma cells exhibiting significantly reduced tumor growth in immunocompromised mice. Here, we used a specific ERK 5 inhibitor, XMD8-92 in various in vitro and in vivo models to demonstrate that inhibition of ERK5 can slow down mesothelioma tumorigenesis. First, we show a dose dependent toxicity of XMD8-92 to 2 human mesothelioma cell lines growing as a monolayer...
January 2, 2018: Oncotarget
https://www.readbyqxmd.com/read/29285799/biological-effects-of-melatonin-on-osteoblast-osteoclast-cocultures-bone-and-quality-of-life-implications-of-a-role-for-mt2-melatonin-receptors-mek1-2-and-mek5-in-melatonin-mediated-osteoblastogenesis
#15
Sifat Maria, Rebekah M Samsonraj, Fahima Munmun, Jessica Glas, Maria Silvestros, Mary P Kotlarczyk, Ryan Rylands, Amel Dudakovic, Andre J van Wijnen, Larry T Enderby, Holly Lassila, Bala Dodda, Vicki L Davis, Judy Balk, Matt Burow, Bruce A Bunnell, Paula A Witt-Enderby
The Melatonin Osteoporosis Prevention Study (MOPS) demonstrated that nightly melatonin resulted in a time-dependent decrease in equilibrium ratios of serum osteoclasts and osteoblasts in perimenopausal women. This study examines mechanisms related to the ratios of osteoblasts and osteoclasts using coculture models (transwell or layered) of human mesenchymal stem cell (MSC) and human peripheral blood monocytes (PBMCs). Human MSC/PBMC cocultures exposed to melatonin in osteogenic (OS+) medium for 21 days induced osteoblast differentiation and mineralization; however, only in layered cocultures did melatonin inhibit osteoclastogenesis...
April 2018: Journal of Pineal Research
https://www.readbyqxmd.com/read/29221196/identification-of-cellular-genes-and-pathways-important-for-tumorigenicity-of-hepatocellular-carcinoma-cell-lines-by-proteomic-profiling
#16
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
#17
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
#18
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
#19
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
#20
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...
January 2018: Molecular Medicine Reports
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