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https://www.readbyqxmd.com/read/28713961/adipose-differentiation%C3%A2-related-protein-knockdown-inhibits-vascular-smooth-muscle-cell-proliferation-and-migration-and-attenuates-neointima-formation
#1
Haomin Zhao, Tao Han, Xin Hong, Dajun Sun
Vascular smooth muscle cells (VSMCs) have an important role in atherosclerosis development. Evidence has demonstrated that adipose differentiation‑related protein (ADRP) is associated with foam cell formation and atherosclerosis progression. However, to the best of our knowledge, no previous studies have investigated the role of ADRP knockdown in platelet‑derived growth factor (PDGF)‑stimulated proliferation and migration of VSMCs in vitro. Furthermore, the effect of ADRP knockdown on neointima formation in vivo remains unclear...
July 15, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28704925/licochalcone-a-prevents-platelet-activation-and-thrombus-formation-through-the-inhibition-of-plc%C3%AE-2-pkc-akt-and-mapk-pathways
#2
Li-Ming Lien, Kuan-Hung Lin, Li-Ting Huang, Mei-Fang Tseng, Hou-Chang Chiu, Ray-Jade Chen, Wan-Jung Lu
Platelet activation is involved in cardiovascular diseases, such as atherosclerosis and ischemic stroke. Licochalcone A (LA), an active ingredient of licorice, exhibits multiple biological activities such as anti-oxidation and anti-inflammation. However, its role in platelet activation remains unclear. Therefore, the study investigated the antiplatelet mechanism of LA. Our data revealed that LA (2-10 μM) concentration dependently inhibited platelet aggregation induced by collagen, but not thrombin and U46619...
July 12, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28699893/hyperactivated-mtorc1-downregulation-of-foxo3a-pdgfr%C3%AE-akt-cascade-restrains-tuberous-sclerosis-complex-associated-tumor-development
#3
Li Wang, Zhaofei Ni, Yujie Liu, Shuang Ji, Fuquan Jin, Keguo Jiang, Junfang Ma, Cuiping Ren, Hongbing Zhang, Zhongdong Hu, Xiaojun Zha
Hyperactivation of mammalian target of rapamycin complex 1 (mTORC1), caused by loss-of-function mutations in either the TSC1 or TSC2 gene, leads to the development of tuberous sclerosis complex (TSC), a benign tumor syndrome with multiple affected organs. mTORC1-mediated inhibition of AKT constrains the tumor progression of TSC, but the exact mechanisms remain unclear. Herein we showed that loss of TSC1 or TSC2 downregulation of platelet-derived growth factor receptor α (PDGFRα) expression was mediated by mTORC1...
July 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28698260/phospholipase-c%C3%AE-1-mediates-intima-formation-through-akt-notch1-signaling-independent-of-the-phospholipase-activity
#4
Dongyang Jiang, Jianhui Zhuang, Wenhui Peng, Yuyan Lu, Hao Liu, Qian Zhao, Chen Chi, Xiankai Li, Guofu Zhu, Xiangbin Xu, Chen Yan, Yawei Xu, Junbo Ge, Jinjiang Pang
BACKGROUND: Vascular smooth muscle cell proliferation, migration, and dedifferentiation are critical for vascular diseases. Recently, it was demonstrated that Notch receptors have opposing effects on intima formation after vessel injury. Therefore, it is important to investigate the specific regulatory pathways that activate the different Notch receptors. METHODS AND RESULTS: There was a time- and dose-dependent activation of Notch1 by angiotensin II and platelet-derived growth factor in vascular smooth muscle cells...
July 11, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28691643/rap2b-promotes-angiogenesis-via-pi3k-akt-vegf-signaling-pathway-in-human-renal-cell-carcinoma
#5
Jiehui Di, Keyu Gao, Debao Qu, Jing Yang, Junnian Zheng
Human renal cell carcinoma which is a highly vascular tumor is the leading cause of death from urologic cancers. Angiogenesis has a pivotal role in oncogenesis and in the viability and expansion of renal cell carcinoma. Rap2B, as a small guanosine triphosphate-binding protein of the Ras family, was first discovered in the early 1990s during the screening of a platelet complementary DNA library. Previous studies have shown that Rap2B aberrantly expressed in human carcinogenesis and promoted the development of tumors via multiple signaling pathways...
July 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28685689/arylurea-derivatives-a-class-of-potential-cancer-targeting-agents
#6
Jia-Nian Chen, De-Wen Wu, Ting Li, Kang-Jian Yang, Li Cheng, Zu-Ping Zhou, Shi-Ming Pu, Wan-Hua Lin
Arylurea derivatives, an important class of small molecules, have received considerable attention in recent years due to their wide range of biological applications. Various molecular targeted agents with arylurea scaffold as potential enzyme/receptor inhibitors were constructed with the successful development of sorafenib and regorafenib. This review focuses on those arylureas possessing anti-cancer activities from 2010 to date. According to their different mechanisms of action, these arylureas are divided into the following six categories: (1) Ras/Raf/MEK/ERK signaling pathway inhibitors; (2) tumor angiogenesis inhibitors, their targets include vascular endothelial growth factor receptors (VEGFRs), fibroblast growth factor receptors (FGFRs), platelet-derived growth factor receptors (PDGFRs), epidermal growth factor receptors (EGFRs), insulin-like growth factor 1 receptor (IGF-1R), Fms-like tyrosine kinase 3 (FLT3), c-Kit, MET, and Smoothened (Smo); (3) PI3K/AKT/mTOR signaling pathway inhibitors; (4) cell cycle inhibitors, their targets include checkpoint kinases (Chks), cyclin-dependent kinases (CDKs), Aurora, SUMO activating enzyme 1 (SUMO E1), tubulin, and DNA; (5) tumor differentiation, migration, and invasion inhibitors, their targets include matrix metalloproteinases (MMPs), LIM kinase (Limk), nicotinamide phosphoribosyltransferase (Nampt), and histone deacetylase (HDAC); (6) arylureas from the rational modification of natural products...
July 7, 2017: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/28666888/antofine-a-natural-phenanthroindolizidine-alkaloid-suppresses-angiogenesis-via-regulation-of-akt-mtor-and-ampk-pathway-in-endothelial-cells-and-endothelial-progenitor-cells-derived-from-mouse-embryonic-stem-cells
#7
Jedo Oh, Gi Dae Kim, Sanghee Kim, Sang Kook Lee
Although antofine, a natural phenanthroindolizidine alkaloid, exerts potential biological activities, including anticancer effect and anti-angiogenic activity, the underlying mechanisms have not yet been investigated. In the present study, the inhibitory effect of antofine on angiogenesis was determined in cultured mouse embryonic stem (mES)/embryoid body (EB)-derived endothelial cells and vascular endothelial growth factor (VEGF)-induced human umbilical vein endothelial cells (HUVECs). Antofine effectively inhibited VEGF-induced cell migration and tube formation of HUVECs...
June 27, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/28660769/platelets-as-a-surrogate-disease-model-of-neurodevelopmental-disorders-insights-from-fragile-x-syndrome
#8
David Pellerin, Audrey Lortie, François Corbin
Fragile X Syndrome (FXS) is the most common inherited form of intellectual disability and the leading monogenic cause of autism spectrum disorders (ASD). Despite a large number of therapeutics developed in past years, there is currently no targeted treatment approved for FXS. In fact, translation of the positive and very promising preclinical findings from animal models to human subjects has so far fallen short owing in part to the low predictive validity of the Fmr1 ko mouse, an overly simplistic model of the complex human disease...
June 29, 2017: Platelets
https://www.readbyqxmd.com/read/28652403/protease-activated-receptor-4-and-p2y12-dimerize-co-internalize-and-activate-akt-signaling-via-endosomal-recruitment-of-%C3%AE-arrestin
#9
Thomas H Smith, Julia G Li, Michael R Dores, JoAnn Trejo
Vascular inflammation and thrombosis requires the concerted actions of several different agonists, many of which act on G protein-coupled receptors (GPCRs). GPCR dimerization is a well-established phenomenon that can alter protomer function. In platelets and other cell types, protease-activated receptor-4 (PAR4) has been shown to dimerize with the purinergic receptor P2Y12 to coordinate β-arrestin-mediated Akt signaling, an important mediator of integrin activation. However, the mechanism by which the PAR4-P2Y12 dimer controls β-arrestin dependent Akt signaling is not known...
June 26, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28650848/ser-thr-protein-kinase-b2-nadph-oxidase-2-signaling-in-thromboinflammation
#10
Jing Li, Jaehyung Cho
PURPOSE OF REVIEW: Interactions between neutrophils and platelets contribute to the progression of thromboinflammatory disease. However, the regulatory mechanism governing these interactions is poorly understood. The present review focuses on the crucial role of Ser/Thr protein kinase B (AKT)2-NADPH oxidase 2 (NOX2) signaling in regulating neutrophil and platelet activation and their heterotypic interactions under thromboinflammatory conditions. RECENT FINDINGS: Growing evidence has shown that platelets, leukocytes, and blood coagulation need to be considered to treat thromboinflammatory disease in which inflammation and thrombosis occur concurrently...
June 24, 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/28650323/the-naphthoquinone-plumbagin-suppresses-adp-induced-rat-platelet-aggregation-through-p2y1-plc-signaling-pathway
#11
Qianrui Zhang, Xiaoyan Liao, Fangjian Wu
Plumbagin (PLB) isolated from Plumbago zeylanica L (Plumbaginaceae) was evaluated for the suppressive effect and mechanism on ADP induced rat platelet aggregation. Adult male SD rats were randomly divided into control group, clopidogrel group, PLB 25mg/kg group and PLB 50mg/kg group. Clopidogrel (13.5mg/kg per day) and PLB (25 and 50mg/kg per day) were orally given to experimental rats by gavage for seven consecutive days. The antiplatelet properties were assessed by measuring the ADP-induced platelet aggregation rate (Aggmax)...
March 2017: Pakistan Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28634089/wedelolactone-a-plant-coumarin-prevents-vascular-smooth-muscle-cell-proliferation-and-injury-induced-neointimal-hyperplasia-through-akt-and-ampk-signaling
#12
Lu Peng, Xuefeng Huang, Xin Jin, Zuo Jing, Lichao Yang, Yu Zhou, Jie Ren, Yun Zhao
Wedelolactone (WDL) is a natural compound derived from Chinese herbal medicine Eclipta prostrate L, and has been reported to exhibit various effects potentially beneficial for human health. However, the possible preventive effects of WDL toward vascular remodeling and mechanisms involved have not been investigated to date. In this study, we investigated the effects of WDL on proliferation induced by platelet-derived growth factor (PDGF) in primary rat aortic smooth muscle cells (VSMCs) and on neointimal hyperplasia resulted from balloon injury in rats...
June 17, 2017: Experimental Gerontology
https://www.readbyqxmd.com/read/28629815/resveratrol-suppresses-pulmonary-tumor-metastasis-by-inhibiting-platelet-mediated-angiogenic-responses
#13
Liwei He, Fangtian Fan, Xianbang Hou, Cuixiang Gao, Li Meng, Shu Meng, Shiwen Huang, Hongyan Wu
BACKGROUND: To explore the impact of Resveratrol (RSV) on the angiogenic potential of activated platelets and to elucidate the underlying mechanism. METHODS: Vascular endothelial growth factor concentrations were measured by enzyme-linked immunosorbent assay. Capillary tube formation assay was used to examine the impact of RSV on the angiogenic potential of activated platelets. The levels of cyclic adenosine monophosphate and cyclic guanosine monophosphate (cGMP) in the supernatant were evaluated using corresponding enzyme-linked immunosorbent assay kits...
May 10, 2017: Journal of Surgical Research
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
#14
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/28577568/pirfenidone-inhibits-myofibroblast-differentiation-and-lung-fibrosis-development-during-insufficient-mitophagy
#15
Yusuke Kurita, Jun Araya, Shunsuke Minagawa, Hiromichi Hara, Akihiro Ichikawa, Nayuta Saito, Tsukasa Kadota, Kazuya Tsubouchi, Nahoko Sato, Masahiro Yoshida, Kenji Kobayashi, Saburo Ito, Yu Fujita, Hirofumi Utsumi, Haruhiko Yanagisawa, Mitsuo Hashimoto, Hiroshi Wakui, Yutaka Yoshii, Takeo Ishikawa, Takanori Numata, Yumi Kaneko, Hisatoshi Asano, Makoto Yamashita, Makoto Odaka, Toshiaki Morikawa, Katsutoshi Nakayama, Kazuyoshi Kuwano
BACKGROUND: Pirfenidone (PFD) is an anti-fibrotic agent used to treat idiopathic pulmonary fibrosis (IPF), but its precise mechanism of action remains elusive. Accumulation of profibrotic myofibroblasts is a crucial process for fibrotic remodeling in IPF. Recent findings show participation of autophagy/mitophagy, part of the lysosomal degradation machinery, in IPF pathogenesis. Mitophagy has been implicated in myofibroblast differentiation through regulating mitochondrial reactive oxygen species (ROS)-mediated platelet-derived growth factor receptor (PDGFR) activation...
June 2, 2017: Respiratory Research
https://www.readbyqxmd.com/read/28576849/proteome-wide-identification-of-glycosylation-dependent-interactors-of-galectin-1-and-galectin-3-on-mesenchymal-retinal-pigment-epithelial-cells
#16
Jara Obermann, Claudia S Priglinger, Juliane Merl-Pham, Arie Geerlof, Sigfried Priglinger, Magdalena Götz, Stefanie M Hauck
Identification of interactors is a major goal in cell biology. Not only protein-protein but also protein-carbohydrate interactions are of high relevance for signal transduction in biological systems. Here we aim to identify novel interacting binding partners for the β-galactoside-binding proteins Galectin-1 (Gal-1) and Galectin-3 (Gal-3) relevant in the context of the eye disease proliferative vitreoretinopathy (PVR). PVR is one of the most common failures after retinal detachment surgeries and is characterized by the migration, adhesion and epithelial-to-mesenchymal transition (EMT) of retinal pigment epithelial cells (RPE) and the subsequent formation of sub- and epiretinal fibrocellular membranes...
June 2, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28511645/therapeutic-potential-of-tas-115-via-c-met-and-pdgfr%C3%AE-signal-inhibition-for-synovial-sarcoma
#17
Shutaro Yamada, Yoshinori Imura, Takaaki Nakai, Sho Nakai, Naohiro Yasuda, Keiko Kaneko, Hidetatsu Outani, Satoshi Takenaka, Kenichiro Hamada, Akira Myoui, Nobuhito Araki, Takafumi Ueda, Kazuyuki Itoh, Hideki Yoshikawa, Norifumi Naka
BACKGROUND: The prognosis of synovial sarcoma (SS), an aggressive soft tissue sarcoma, remains poor. We previously reported that c-MET or platelet-derived growth factor receptor α (PDGFRα) signalling pathway is related to SS progression based upon the findings of phospho-receptor tyrosine kinase (RTK) arrays. TAS-115 is a novel c-MET/ vascular endothelial growth factor receptor-targeting tyrosine kinase inhibitor that has been shown to inhibit multiple RTKs. Here we aimed to investigate the therapeutic potential of TAS-115 against SS...
May 16, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28504693/cyclin-dependent-kinase-7-is-a-therapeutic-target-in-high-grade-glioma
#18
S A Greenall, Y C Lim, C B Mitchell, K S Ensbey, B W Stringer, A L Wilding, G M O'Neill, K L McDonald, D J Gough, B W Day, T G Johns
High-grade glioma (HGG) is an incurable brain cancer. The transcriptomes of cells within HGG tumors are highly heterogeneous. This renders the tumors unresponsive or able to adapt to therapeutics targeted at single pathways, thereby causing treatment failure. To overcome this, we focused on cyclin-dependent kinase 7 (CDK7), a ubiquitously expressed molecule involved in two major drivers of HGG pathogenesis: cell cycle progression and RNA polymerase-II-based transcription. We tested the activity of THZ1, an irreversible CDK7 inhibitor, on patient-derived primary HGG cell lines and ex vivo HGG patient tissue slices, using proliferation assays, microarray analysis, high-resolution respirometry, cell cycle analysis and in vivo tumor orthografts...
May 15, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28497199/arachidonic-acid-induces-are-nrf2-dependent-heme-oxygenase-1-transcription-in-rat-brain-astrocytes
#19
Chih-Chung Lin, Chien-Chung Yang, Yu-Wen Chen, Li-Der Hsiao, Chuen-Mao Yang
Arachidonic acid (AA) is a major product of phospholipid hydrolysis catalyzed by phospholipase A2 during neurodegenerative diseases. AA exerts as a second messenger to regulate various signaling components which may be involved in different pathophysiological processes. Astrocytes are the main types of CNS resident cells which maintain and support the physiological function of brain. AA has been shown to induce ROS generation through activation of NADPH oxidases (Noxs) which may play a key role in the expression of heme oxygenase-1 (HO-1)...
May 11, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28492699/lipopolysaccharide-as-trigger-of-platelet-aggregation-via-eicosanoid-over-production
#20
Cristina Nocella, Roberto Carnevale, Simona Bartimoccia, Marta Novo, Roberto Cangemi, Daniele Pastori, Camilla Calvieri, Pasquale Pignatelli, Francesco Violi
The effect of lipopolysaccharide (LPS) on platelet aggregation is still controversial. We performed in vitro and ex vivo studies in controls and in patients with community-acquired pneumonia (CAP) to assess the effect of LPS on platelet activation (PA). LPS (15-100 pg/ml) significantly increased PA only if combined with sub-threshold concentrations (STC) of collagen or ADP; this effect was associated with increased platelet H2O2 production, Nox2 activation, PLA2 phosphorylation, thromboxane (Tx)A2 and 8-iso-PGF2α-III, and was inhibited by aspirin, TxA2 receptor antagonist or by Toll-like receptor 4 blocking peptide (TLR4bp)...
May 11, 2017: Thrombosis and Haemostasis
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