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https://www.readbyqxmd.com/read/28072855/sdf-1%C3%AE-cxcr4-signaling-in-lipid-rafts-induces-platelet-aggregation-via-pi3-kinase-dependent-akt-phosphorylation
#1
Hiroko Ohtsuka, Tomohiro Iguchi, Moyuru Hayashi, Mizuho Kaneda, Kazuko Iida, Motoyuki Shimonaka, Takahiko Hara, Morio Arai, Yuichi Koike, Naomasa Yamamoto, Kohji Kasahara
Stromal cell-derived factor-1α (SDF-1α)-induced platelet aggregation is mediated through its G protein-coupled receptor CXCR4 and phosphatidylinositol 3 kinase (PI3K). Here, we demonstrate that SDF-1α induces phosphorylation of Akt at Thr308 and Ser473 in human platelets. SDF-1α-induced platelet aggregation and Akt phosphorylation are inhibited by pretreatment with the CXCR4 antagonist AMD3100 or the PI3K inhibitor LY294002. SDF-1α also induces the phosphorylation of PDK1 at Ser241 (an upstream activator of Akt), GSK3β at Ser9 (a downstream substrate of Akt), and myosin light chain at Ser19 (a downstream element of the Akt signaling pathway)...
2017: PloS One
https://www.readbyqxmd.com/read/28054640/honokiol-as-a-specific-collagen-receptor-glycoprotein-vi-antagonist-on-human-platelets-functional-ex-vivo-and-in-vivo-studies
#2
Tzu-Yin Lee, Chao-Chien Chang, Wan-Jung Lu, Ting-Lin Yen, Kuan-Hung Lin, Pitchairaj Geraldine, Jiun-Yi Li, Joen-Rong Sheu
Honokiol, derived from Magnolia officinalis, has various pharmacological properties. Platelet activation plays a critical role in cardiovascular diseases. Honokiol has been reported to inhibit collagen-stimulated rabbit platelet aggregation. However, detailed further studies on the characteristics and functional activity of honokiol in platelet activation are relatively lacking. In the present study, honokiol specifically inhibited platelet aggregation and Ca(+2) ion mobilization stimulated with collagen or convulxin, an agonist of glycoprotein (GP) VI, but not with aggretin, an agonist of integrin α2β1...
January 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28011478/validation-of-vx2-as-a-hepatocellular-carcinoma-model-comparison-of-the-molecular-reaction-of-vx2-and-hepg2-tumor-cells-to-sorafenib-in-vitro
#3
Norbert Nass, Sebastian Streit, Christian Wybranski, Julian Jürgens, Jan Brauner, Nadine Schulz, Maciej Powerski, Jens Ricke, Thomas Kalinski, Oliver Dudeck, Max Seidensticker
As there is currently no superior hepatocellular carcinoma (HCC) model with percutaneous vascular access for transarterial treatments available, the VX2 rabbit model is frequently used for in vivo investigations on liver carcinoma. However, the VX2 cell line was derived from a virus-induced skin papilloma that can form carcinosarcoma in liver of rabbits and the transferability of obtained results to HCC treatment remains open. Here we compared the most frequently investigated human HCC model cell line, HepG2, with VX2 cells in vitro in terms of sensitivity towards the broad specificity kinase inhibitor sorafenib and responsiveness to the addition of platelet-derived growth factor AB (PDGF-AB), vascular endothelial growth factor (VEGF) and hepatic growth factor (HGF), as well as insulin and interleukin-1β (IL1β)...
January 2017: Anticancer Research
https://www.readbyqxmd.com/read/27983763/the-common-dietary-flavonoid-myricetin-attenuates-liver-fibrosis-in-carbon-tetrachloride-treated-mice
#4
Yan Geng, Qing Sun, Wang Li, Zhen-Ming Lu, Hong-Yu Xu, Jin-Song Shi, Zheng-Hong Xu
SCOPE: Myricetin is found in most berries, vegetables, and various medicinal herbs, which has been reported to possess various bio-activities. However, the role of myricetin on liver fibrosis remains to be elucidated. METHODS AND RESULTS: Hepatic stellate cell (HSC) line CFSC-8B was stimulated by transforming growth factor-β1 (TGF-β1) or Platelet-derived growth factor-BB (PDGF-BB) to induce liver fibrosis in vitro. The results showed that myricetin significantly ameliorated TGF-β1 or PDGF-BB induced HSCs activation, cell migration, and extracellular matrix (ECM) production, blocked TGF-β1 induced phosphorylation of Smad2, P38, extracellular signal-regulated kinase (ERK) and Protein kinase B (AKT), and down-regulated PDGF-BB stimulated phosphorylation of ERK and AKT in HSCs in a dose-dependent manner...
December 16, 2016: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/27965317/cell-specific-computational-modeling-of-the-pim-pathway-in-acute-myeloid-leukemia
#5
Dana Silverbush, Shaun Grosskurth, Dennis Wang, Francoise Powell, Berthold Gottgens, Jonathan Dry, Jasmin Fisher
Personalized therapy is a major goal of modern oncology, as patient responses vary greatly even within a histologically defined cancer subtype. This is especially true in acute myeloid leukemia (AML), which exhibits striking heterogeneity in molecular segmentation. When calibrated to cell-specific data, executable network models can reveal subtle differences in signaling that help explain differences in drug response. Furthermore, they can suggest drug combinations to increase efficacy and combat acquired resistance...
December 13, 2016: Cancer Research
https://www.readbyqxmd.com/read/27959381/nobiletin-a-citrus-flavonoid-activates-vasodilator-stimulated-phosphoprotein-in-human-platelets-through-non-cyclic-nucleotide-related-mechanisms
#6
Thanasekaran Jayakumar, Kao-Chang Lin, Wan-Jung Lu, Chia-Ying Lin, Geraldine Pitchairaj, Jiun-Yi Li, Joen-Rong Sheu
Nobiletin, a bioactive polymethoxylated flavone, has been described to possess a diversity of biological effects through its antioxidant and anti-inflammatory properties. Vasodilator-stimulated phosphoprotein (VASP) is a common substrate for cyclic AMP and cyclic GMP-regulated protein kinases [i.e., cyclic AMP-dependent protein kinase (PKA; also known as protein kinase A) and cyclic GMP-dependent protein kinase (PKG; also known as protein kinase G)] and it has been shown to be directly phosphorylated by protein kinase C (PKC)...
January 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/27943621/the-protective-effect-of-human-platelet-lysate-in-models-of-neurodegenerative-disease-involvement-of-the-akt-and-mek-pathways
#7
Flore Gouel, Bruce Do Van, Ming-Li Chou, Aurélie Jonneaux, Caroline Moreau, Régis Bordet, Thierry Burnouf, Jean-Christophe Devedjian, David Devos
Neurodegenerative diseases have huge economic and societal impacts, and place an immense emotional burden on patients and caregivers. Given that platelets have an essential physiological role in wound healing and tissue repair, human platelet lysates (HPLs) are being developed as a novel, effective biotherapy for neurodegenerative diseases. HPLs constitute abundant, readily accessible sources of physiological mixtures of many growth factors (GFs), with demonstrable effects on neuron survival and thus the development, maintenance, function and plasticity of the vertebrate nervous system...
December 12, 2016: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/27936141/hbs-binding-to-gp1b%C3%AE-activates-platelets-in-sickle-cell-disease
#8
Gowtham K Annarapu, Rashi Singhal, Avinash Gupta, Sheetal Chawla, Harish Batra, Tulika Seth, Prasenjit Guchhait
Intravascular hemolysis increases the risk of thrombosis in hemolytic disorders. Our previous study showed that the binding of adult hemoglobin (HbA) to glycoprotein (GP) 1bα induced the activation of platelets. The elevated plasma Hb or platelet surface bound Hb positively correlated with platelet activation in patients with paroxysmal nocturnal hemoglobinuria (PNH). Furthermore, this study shows that the sickle Hb [HbS, occurs due to single nucleotide polymorphism at A>T of β-globin gene of Hb and causes sickle cell disease (SCD)] also bound to GP1bα and activated platelets in a concentration-dependent manner...
2016: PloS One
https://www.readbyqxmd.com/read/27922691/microarray-expression-profiles-of-genes-in-lung-tissues-of-rats-subjected-to-focal-cerebral-ischemia-induced-lung-injury-following-bone-marrow-derived-mesenchymal-stem-cell-transplantation
#9
Yue Hu, Liu-Lin Xiong, Piao Zhang, Ting-Hua Wang
Ischemia-induced stroke is the most common disease of the nervous system and is associated with a high mortality rate worldwide. Cerebral ischemia may lead to remote organ dysfunction, particular in the lungs, resulting in lung injury. Nowadays, bone marrow-derived mesenchymal stem cells (BMSCs) are widely studied in clinical trials as they may provide an effective solution to the treatment of neurological and cardiac diseases; however, the underlying molecular mechanisms remain unknown. In this study, a model of permanent focal cerebral ischemia-induced lung injury was successfully established and confirmed by neurological evaluation and lung injury scores...
January 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/27908414/licl-regulates-mitochondrial-biogenesis-during-megakaryocyte-development
#10
Ram Babu Undi, Usha Gutti, Ravi Kumar Gutti
JAK-STAT, PI3K-AKT and MAPK signaling pathways are involved in platelet production process. Although wnt signaling has been reported in the biogenesis of platelets, but its role in megakaryocyte development is not well studied. We used an inducible canonical wnt signaling system that utilizes LiCl (GSK-3β inhibitor). LiCl could activate wnt signaling pathway along with maturation of megakaryocytes. Mitochondrial staining showed an increase in mitochondrial mass upon induction with LiCl. Also, mitochondrial markers PGC-1α and TFAM were up regulated with increase in mitochondrial DNA content...
January 2017: Journal of Trace Elements in Medicine and Biology
https://www.readbyqxmd.com/read/27896950/ppar%C3%AE-agonists-negatively-regulate-%C3%AE-iib%C3%AE-3-integrin-outside-in-signalling-and-platelet-function-through-upregulation-of-protein-kinase-a-activity
#11
A J Unsworth, N Kriek, A P Bye, K Naran, T Sage, G D Flora, J M Gibbins
BACKGROUND: Agonists for the peroxisome proliferator activated receptor PPARγ, have been shown to have inhibitory effects on platelet activity following stimulation by GPVI and GPCR agonists. OBJECTIVES: Profound effects on thrombus formation led us to suspect a role for PPARγ agonists in the regulation of integrin αIIbβ3 mediated signalling. Both GPVI and GPCR signalling pathways lead to αIIbβ3 activation, and signalling through αIIbβ3 plays a critical role in platelet function and normal haemostasis...
November 29, 2016: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/27886249/impairment-of-pdgf-induced-chemotaxis-by-extracellular-%C3%AE-synuclein-through-selective-inhibition-of-rac1-activation
#12
Taro Okada, Chihoko Hirai, Shaymaa Mohamed Mohamed Badawy, Lifang Zhang, Taketoshi Kajimoto, Shun-Ichi Nakamura
Parkinson's disease (PD) is characterized by α-synuclein (α-Syn)-positive intracytoplasmic inclusions, known as Lewy bodies. Although it is known that extracellular α-Syn is detected in the plasma and cerebrospinal fluid, its physiological significance remains unclear. Here, we show that extracellular α-Syn suppresses platelet-derived growth factor (PDGF)-induced chemotaxis in human neuroblastoma SH-SY5Y cells. The inhibitory effect was stronger in the mutant α-Syn(A53T), found in hereditary PD, and the degree of inhibition was time-dependent, presumably because of the oligomerization of α-Syn...
November 25, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27885699/strains-of-group-b-streptococci-from-septic-patients-induce-platelet-activation-via-toll-like-receptor-2
#13
Xiaoyan Liu, Hongyun Liu, Xianming Luo, Ping Zhang, Yanmin Gao, Shuangfeng Xie, Kang Xu, Jianxing Chang, Liping Ma
Group B Streptococcus (GBS) causes life-threatening bacterial sepsis, especially in newborns and pregnant women. Patients suffering from sepsis often display low platelet counts, characterized by thrombocytopenia, because of platelet activation. In the present study, the roles of six GBS strains from septic patients in platelet aggregation, as well as the underlying mechanisms, were investigated. Incubation of platelets with three of the strains induced platelet aggregation, increased the secretion of cellular adhesin molecule CD62P and activation of GPIIb/IIIa...
November 25, 2016: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/27876620/the-gabab-positive-allosteric-modulators-cgp7930-and-gs39783-stimulate-erk1-2-signalling-in-cells-lacking-functional-gabab-receptors
#14
Maria C Olianas, Simona Dedoni, Pierluigi Onali
The present study shows that the GABAB positive allosteric modulators (PAMs) CGP7930 and GS39783 stimulate extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) signalling in cells that do not express functional GABAB receptors. In human SH-SY5Y neuroblastoma cells, CGP7930 and GS39783 induced a time- and concentration-dependent increase in ERK1/2 phosphorylation with potencies similar to those displayed as GABAB PAMs. Conversely, γ-aminobutyric acid and the GABAB receptor agonists (-)baclofen and SKF97541 were completely inactive...
January 5, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/27873355/isoquercitrin-protects-against-pulmonary-hypertension-via-inhibiting-pasmcs-proliferation
#15
Yongtao Zhang, Yuqian Cui, Wei Deng, Hao Wang, Weidong Qin, Chengmin Huang, Chen Li, Jianning Zhang, Yuan Guo, Dawei Wu, Haipeng Guo
Pulmonary vascular remodeling is a common feature among the heterogeneous disorders that cause pulmonary arterial hypertension (PAH), and pulmonary arterial smooth muscle cells (PASMCs) proliferation impact the long-term prognosis of the patient. Isoquercitrin (IQC) is a flavonoid with anti-oxidative, anti-inflammatory and anti-proliferative activations. This study aimed to investigate whether IQC could prevent PASMCs proliferation and vascular remodeling in monocrotaline (MCT) induced PAH. Male Wistar rats were administered with vehicle or 0...
November 22, 2016: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/27845909/platelet-derived-growth-factor-receptor-alpha-mediates-nodal-metastases-in-papillary-thyroid-cancer-by-driving-the-epithelial-mesenchymal-transition
#16
Esther Ekpe-Adewuyi, Ana Lopez-Campistrous, Xiaoyun Tang, David N Brindley, Todd P W McMullen
Recently platelet derived growth factor receptor-alpha (PDGFRα) was recognized as a potential target to treat aggressive papillary thyroid cancer given its strong association with lymph node metastases. However, it is unclear how PDGFRα potentiates metastases and if it works through the canonical MAPK pathway traditionally linked to PTC oncogenesis. We explored the phenotypic changes driven by PDGFRα activation in human papillary thyroid cancer (PTC) cells and the downstream signalling cascades through which they are effected...
November 11, 2016: Oncotarget
https://www.readbyqxmd.com/read/27844272/resistance-to-targeted-therapies-in-renal-cancer-the-importance-of-changing-the-mechanism-of-action
#17
I Duran, J Lambea, P Maroto, J L González-Larriba, Luis Flores, S Granados-Principal, M Graupera, B Sáez, A Vivancos, O Casanovas
Renal cell carcinoma (RCC) is a complex disease characterized by mutations in several genes. Loss of function of the von Hippel-Lindau (VHL) tumour suppressor gene is a very common finding in RCC and leads to up-regulation of hypoxia-inducible factor (HIF)-responsive genes accountable for angiogenesis and cell growth, such as platelet-derived growth factor (PDGF) and vascular endothelial growth factor (VEGF). Binding of these proteins to their cognate tyrosine kinase receptors on endothelial cells promotes angiogenesis...
November 15, 2016: Targeted Oncology
https://www.readbyqxmd.com/read/27825105/mir-184-exhibits-angiostatic-properties-via-regulation-of-akt-and-vegf-signaling-pathways
#18
Jong Kook Park, Han Peng, Wending Yang, Julia Katsnelson, Olga Volpert, Robert M Lavker
Corneal avascularity is critical for achieving transparency necessary for proper transmission of light to the lens and visual acuity. Although much is known about angiogenesis and angiostasis, the precise regulation of these processes in the cornea is unclear. MicroRNA (miR)-184, the most abundant corneal epithelial miRNA, has been suggested to function in corneal angiostasis by altering VEGF signaling; however, the mechanism(s) underlying this regulation have not been addressed. Using a combination of in vitro and in vivo assays to evaluate angiogenesis, we demonstrated that human limbal epithelial keratinocytes (HLEKs) engineered to overexpress miR-184 secreted lower amounts of angiogenic mitogens...
January 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/27821588/smooth-muscle-cell-proangiogenic-phenotype-induced-by-cyclopentenyl-cytosine-promotes-endothelial-cell-proliferation-and-migration
#19
Rui Tang, Gui Zhang, Shi-You Chen
Vascular smooth muscle cells (SMCs) and endothelial cells (ECs) are in close contact with blood vessels. SMC phenotypes can be altered during pathological vascular remodeling. However, how SMC phenotypes affect EC properties remains largely unknown. In this study, we found that PDGF-BB-induced synthetic SMCs suppressed EC proliferation and migration while exhibiting increased expression of anti-angiogenic factors, such as endostatin, and decreased pro-angiogenic factors, including CXC motif ligand 1 (CXCL1)...
December 23, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27821539/endothelial-microparticles-from-acute-coronary-syndrome-patients-induce-premature-coronary-artery-endothelial-cells-ageing-and-thrombogenicity-role-of-the-ang-ii-at1-receptor-nadph-oxidase-mediated-activation-of-mapks-and-pi3-kinase-pathways
#20
Malak Abbas, Laurence Jesel, Cyril Auger, Lamia K Amoura, Nathan Messas, Guillaume Manin, Cordula Rumig, Antonio J León-González, Thais P Ribeiro, Grazielle C Silva, Raghida Abou-Merhi, Eva Hamade, Markus Hecker, Yannick Georg, Nabil Chakfe, Patrick Ohlmann, Valérie B Schini-Kerth, Florence Toti, Olivier Morel
BACKGROUND: -Microparticles (MPs) have emerged as a surrogate marker of endothelial dysfunction and cardiovascular risk. This study examined the potential of MPs from senescent endothelial cells (ECs) or from patients with acute coronary syndrome (ACS) to promote premature ECs ageing and thrombogenicity. METHODS: -Primary porcine coronary ECs were isolated from the left circumflex coronary artery. MPs were prepared from ECs and venous blood from patients with ACS (n=30) and from healthy volunteers (n=6) by sequential centrifugation...
November 7, 2016: Circulation
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