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https://www.readbyqxmd.com/read/27908414/licl-regulates-mitochondrial-biogenesis-during-megakaryocyte-development
#1
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
#2
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
#3
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
#4
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
#5
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...
November 19, 2016: European Journal of Pharmacology
https://www.readbyqxmd.com/read/27873355/isoquercitrin-protects-against-pulmonary-hypertension-via-inhibiting-pasmcs-proliferation
#6
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
#7
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
#8
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
#9
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...
October 7, 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/27821588/smooth-muscle-cell-pro-angiogenic-phenotype-induced-by-cyclopentenyl-cytosine-promotes-endothelial-cell-proliferation-and-migration
#10
Rui Tang, Gui Zhang, Shi-You Chen
Vascular smooth muscle cells (SMCs) and endothelial cells (ECs) have a close contact with the blood vessel. SMC phenotypes can be altered during pathological vascular remodeling. However, how SMC phenotypes affect EC properties remain largely unknown. In the present study, we found that platelet-derived growth factor (PDGF)-BB-induced synthetic SMC suppressed EC proliferation and migration while exhibiting an increased expression of anti-angiogenic factors such as endostatin and decreased pro-angiogenic factors including C-X-C motif ligand 1 (CXCL1)...
November 7, 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
#11
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
https://www.readbyqxmd.com/read/27806344/pleiotrophin-enhances-pdgfb-induced-gliomagenesis-through-increased-proliferation-of-neural-progenitor-cells
#12
Lei Zhang, Liisi Laaniste, Yiwen Jiang, Irina Alafuzoff, Lene Uhrbom, Anna Dimberg
Pleiotrophin (PTN) augments tumor growth by increasing proliferation of tumor cells and promoting vascular abnormalization, but its role in early gliomagenesis has not been evaluated. Through analysis of publically available datasets, we demonstrate that increased PTN mRNA expression is associated with amplification of chromosome 7, identified as one of the earliest steps in glioblastoma development. To elucidate the role of PTN in tumor initiation we employed the RCAS/tv-a model that allows glioma induction by RCAS-virus mediated expression of oncogenes in neural progenitor cells...
October 28, 2016: Oncotarget
https://www.readbyqxmd.com/read/27784964/embryonic-liver-fordin-is-involved-in-glucose-glycolysis-of-hepatic-stellate-cell-by-regulating-pi3k-akt-signaling
#13
Wei Tu, Jin Ye, Zhi-Jun Wang
AIM: To investigate the role of embryonic liver fordin (ELF) in liver fibrosis by regulating hepatic stellate cells (HSCs) glucose glycolysis. METHODS: The expression of ELF and the glucose glycolysis-related proteins were evaluated in activated HSCs. siRNA was used to silence ELF expression in activated HSCs in vitro and the subsequent changes in PI3K/Akt signaling and glucose glycolysis-related proteins were observed. RESULTS: The expression of ELF increased remarkably in HSCs of the fibrosis mouse model and HSCs that were cultured for 3 wk in vitro...
October 14, 2016: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/27784380/-platelets-decrease-the-sensitivity-of-leukemia-cell-l1210-to-multiple-drugs-via-activiting-the-akt-and-erk-signalling-pathway
#14
Ya-Bin Hu, Lian-Bo Shao, Lu Zhao, Ying Shen, Kun Wu, Yi-Qiang Wang
OBJECTIVE: To explore the effect of platelets on signal transducers and the sensitivity of leukemia cells to chemotherapeuticl drugs in leukemia cells L1210. METHODS: Murine platelets were prepared and cocultured with leukemia L1210 cells, and the aggregation between them was observed by flow cytometry. The levels of several transducer proteins in leukemia cells were analyzed with Western blot. In some experiments, methotrexate, vincristine or doxorubicin was added to the coculture system and the cell proliferation was measured by using CCK8 colorigenic methods to detect the sensitivity of leukemia cells to the therapeuticals drugs...
October 2016: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/27764761/human-platelet-lysate-versus-minoxidil-stimulates-hair-growth-by-activating-anagen-promoting-signaling-pathways
#15
Maryam Dastan, Nowruz Najafzadeh, Ali Abedelahi, Mohammadreza Sarvi, Ali Niapour
Minoxidil and human platelet lysate (HPL) are commonly used to treat patients with hair loss. However, the roles of HPL versus minoxidil in hair follicle biology largely remain unknown. Here, we hypothesized that bulge and dermal papilla (DP) cells may express specific genes, including Kras, Erk, Akt, Shh and β-catenin after exposure to minoxidil or HPL. The mouse hair follicles were isolated on day 10 after depilation and bulge or DP regions were dissected. The bulge and DP cells were cultured for 14days in DMEM/F12 medium...
October 17, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27758820/arq-092-an-orally-available-selective-akt-inhibitor-attenuates-neutrophil-platelet-interactions-in-sickle-cell-disease
#16
Kyungho Kim, Jing Li, Andrew Barazia, Alan Tseng, Seock-Won Youn, Giovanni Abbadessa, Yi Yu, Brian Schwartz, Robert K Andrews, Victor R Gordeuk, Jaehyung Cho
Previous studies identified the Ser/Thr protein kinase, AKT, as a therapeutic target for thromboinflammatory diseases. Here we report that specific inhibition of AKT with ARQ 092, an orally-available AKT inhibitor currently in Phase Ib clinical trials as an anti-cancer drug, attenuates the adhesive function of neutrophils and platelets from sickle cell disease patients in vitro and cell-cell interactions in a mouse model of sickle cell disease. Studies using neutrophils and platelets isolated from sickle cell disease patients revealed that treatment with 50-500 nM ARQ 092 significantly blocks αMβ2 integrin function in neutrophils and reduces P-selectin exposure and glycoprotein Ib/IX/V-mediated agglutination in platelets...
October 6, 2016: Haematologica
https://www.readbyqxmd.com/read/27748810/evodiamine-inhibits-pdgf%C3%A2-bb%C3%A2-induced-proliferation-of-rat-vascular-smooth-muscle-cells-through-the-suppression-of-cell-cycle-progression-and-oxidative-stress
#17
Xie Ge, Si-Yu Chen, Mei Liu, Ting-Ming Liang, Chang Liu
Vascular smooth muscle cell (VSMC) proliferation is a key event in the development of in‑stent restenosis. Evodiamine is an indole alkaloid extracted from the Chinese medicine, evodia, and has been shown to inhibit tumor cell proliferation and protect the cardiovascular system. However, whether evodiamine affects VSMC proliferation remains to be elucidated. Therefore, the present study examined the effects and the mechanisms of action of evodiamine on the proliferation of rat VSMCs. The cells were treated with evodiamine alone or in combination with platelet‑derived growth factor‑BB (PDGF‑BB) stimulation...
November 2016: Molecular Medicine Reports
https://www.readbyqxmd.com/read/27729247/high-fructose-mediated-attenuation-of-insulin-receptor-signaling-does-not-affect-pdgf-induced-proliferative-signaling-in-vascular-smooth-muscle-cells
#18
Islam Osman, Ninu Poulose, Vadivel Ganapathy, Lakshman Segar
Insulin resistance is associated with accelerated atherosclerosis. Although high fructose is known to induce insulin resistance, it remains unclear as to how fructose regulates insulin receptor signaling and proliferative phenotype in vascular smooth muscle cells (VSMCs), which play a major role in atherosclerosis. Using human aortic VSMCs, we investigated the effects of high fructose treatment on insulin receptor substrate-1 (IRS-1) serine phosphorylation, insulin versus platelet-derived growth factor (PDGF)-induced phosphorylation of Akt, S6 ribosomal protein, and extracellular signal-regulated kinase (ERK), and cell cycle proteins...
November 15, 2016: European Journal of Pharmacology
https://www.readbyqxmd.com/read/27687726/psoralen-and-ultraviolet-a-light-treatment-directly-affects-phosphatidylinositol-3-kinase-signal-transduction-by-altering-plasma-membrane-packing
#19
Britt Van Aelst, Rosalie Devloo, Pierre Zachée, Ruben t'Kindt, Koen Sandra, Philippe Vandekerckhove, Veerle Compernolle, Hendrik B Feys
Psoralen and ultraviolet A light (PUVA) are used to kill pathogens in blood products and as a treatment of aberrant cell proliferation in dermatitis, cutaneous T-cell lymphoma, and graft-versus-host disease. DNA damage is well described, but the direct effects of PUVA on cell signal transduction are poorly understood. Because platelets are anucleate and contain archetypal signal transduction machinery, they are ideally suited to address this. Lipidomics on platelet membrane extracts showed that psoralen forms adducts with unsaturated carbon bonds of fatty acyls in all major phospholipid classes after PUVA...
November 18, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27659217/exosomes-derived-from-akt-modified-human-umbilical-cord-mesenchymal-stem-cells-improve-cardiac-regeneration-and-promote-angiogenesis-via-activating-platelet-derived-growth-factor-d
#20
Jie Ma, Yuanyuan Zhao, Li Sun, Xiaochun Sun, Xiaosu Zhao, Xiaoxian Sun, Hui Qian, Wenrong Xu, Wei Zhu
: : We have previously demonstrated the cardioprotective effects of exosomes derived from mesenchymal stem cells (MSCs). It is well-known that the activation of Akt is involved in stem cell-induced cardioprotection. In the present study, we investigated whether exosomes released from Akt-overexpressing MSCs showed a beneficial effect on cardioprotection and angiogenesis. MSCs were collected from human umbilical cord (hucMSCs), and Akt was transfected into hucMSCs (Akt-hucMSCs) by using an adenovirus transfection system...
September 22, 2016: Stem Cells Translational Medicine
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