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https://www.readbyqxmd.com/read/28817667/glycoprotein-ib-activation-by-thrombin-stimulates-the-energy-metabolism-in-human-platelets
#1
Norma Corona de la Peña, Manuel Gutiérrez-Aguilar, Ileana Hernández-Reséndiz, Álvaro Marín-Hernández, Sara Rodríguez-Enríquez
Thrombin-induced platelet activation requires substantial amounts of ATP. However, the specific contribution of each ATP-generating pathway i.e., oxidative phosphorylation (OxPhos) versus glycolysis and the biochemical mechanisms involved in the thrombin-induced activation of energy metabolism remain unclear. Here we report an integral analysis on the role of both energy pathways in human platelets activated by several agonists, and the signal transducing mechanisms associated with such activation. We found that thrombin, Trap-6, arachidonic acid, collagen, A23187, epinephrine and ADP significantly increased glycolytic flux (3-38 times vs...
2017: PloS One
https://www.readbyqxmd.com/read/28808297/secretory-phospholipase-a2-modified-hdl-rapidly-and-potently-suppresses-platelet-activation
#2
Sanja Curcic, Michael Holzer, Lisa Pasterk, Eva Knuplez, Thomas O Eichmann, Saša Frank, Robert Zimmermann, Rudolf Schicho, Akos Heinemann, Gunther Marsche
Levels of secretory phospholipases A2 (sPLA2) highly increase under acute and chronic inflammatory conditions. sPLA2 is mainly associated with high-density lipoproteins (HDL) and generates bioactive lysophospholipids implicated in acute and chronic inflammatory processes. Unexpectedly, pharmacological inhibition of sPLA2 in patients with acute coronary syndrome was associated with an increased risk of myocardial infarction and stroke. Given that platelets are key players in thrombosis and inflammation, we hypothesized that sPLA2-induced hydrolysis of HDL-associated phospholipids (sPLA2-HDL) generates modified HDL particles that affect platelet function...
August 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28801734/fibrinogen-promotes-malignant-biological-tumor-behavior-involving-epithelial-mesenchymal-transition-via-the-p-akt-p-mtor-pathway-in-esophageal-squamous-cell-carcinoma
#3
Fei Zhang, Yun Wang, Peng Sun, Zhi-Qiang Wang, De-Shen Wang, Dong-Sheng Zhang, Feng-Hua Wang, Jian-Hua Fu, Rui-Hua Xu, Yu-Hong Li
PURPOSE: Hyperfibrinogenemia is associated with unfavorable prognosis and advanced tumor behavior in various malignancies, including esophageal squamous cell carcinoma (ESCC). However, its biological function in ESCC is unknown. The present study was designed to further validate the prognostic value of preoperative plasma hyperfibrinogenemia and evaluate the biological role of fibrinogen, as well as the underlying mechanism in ESCC. METHODS: Data from 452 cases with newly diagnosed ESCC followed by curative surgery between 2006 and 2010 were retrospectively evaluated...
August 11, 2017: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/28783756/pkc-epsilon-deficiency-alters-progenitor-cell-populations-in-favor-of-megakaryopoiesis
#4
John C Kostyak, Elisabetta Liverani, Satya P Kunapuli
BACKGROUND: It has long been postulated that Protein Kinase C (PKC) is an important regulator of megakaryopoiesis. Recent contributions to the literature have outlined the functions of several individual PKC isoforms with regard to megakaryocyte differentiation and platelet production. However, the exact role of PKCε remains elusive. OBJECTIVE: To delineate the role of PKCε in megakaryopoiesis. APPROACH AND RESULTS: We used a PKCε knockout mouse model to examine the effect of PKCε deficiency on platelet mass, megakaryocyte mass, and bone marrow progenitor cell distribution...
2017: PloS One
https://www.readbyqxmd.com/read/28766166/rhpdgf-bb-combined-with-adscs-in-the-treatment-of-achilles-tendinitis-via-mir-363-pi3%C3%A2-k-akt-pathway
#5
Qiao-Jie Chen, Liang Chen, Shao-Kun Wu, Yao-Jun Wu, Qing-Jiang Pang
To investigate the mechanism of recombinant human platelet-derived growth factor-BB (rhPDGF-BB) and human adipose-derived stem cells (hADSCs) in the treatment of Achilles tendinitis. Biomechanical indices of stiffness, stress, and maximum load-to-failure were detected by biomechanical test. mRNA and protein levels of miR-363, p-PI3K/AKT, tendon-related genes Collagen I, Scleraxis (Scx), and Tenascin C (TNC) were measured by qRT-PCR and western blot. The proliferation of hADSCs was accessed by MTT assay. Biomechanical indices of stiffness, stress, and maximum load-to-failure, and mRNA and protein levels of tendon-related genes could be improved by rhPDGF-BB or hADSCs alone, and could be further improved by rhPDGF-BB + hADSCs...
August 1, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28765904/osthole-protects-against-inflammation-in-a-rat-model-of-chronic-kidney-failure-via-suppression-of-nuclear-factor-%C3%AE%C2%BAb-transforming-growth-factor-%C3%AE-1-and-activation-of-phosphoinositide-3-kinase-protein-kinase-b-nuclear-factor-erythroid-derived-2-like-2-signaling
#6
Tao Huang, Zhen Dong
Multiple pharmacological applications of osthole have been previously recognized, including antioxidant, anti-inflammatory, anti‑platelet and estrogenic effects, and resistance to pain. The present study investigated the protective effects of osthole against inflammation in a rat model of chronic kidney failure (CRF) and the underlying mechanisms. Osthole treatment with significantly reversed CRF‑induced changes in serum creatinine, calcium, phosphorus and blood urea nitrogen levels in CRF rats. Male Sprague‑Dawley rats (age, 8 weeks) received 200 mg/kg 2% adenine suspension to induce CRF in the model group...
August 1, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28753204/ask1-facilitates-tumor-metastasis-through-phosphorylation-of-an-adp-receptor-p2y12-in-platelets
#7
Miki Kamiyama, Toshiaki Shirai, Shogo Tamura, Katsue Suzuki-Inoue, Shogo Ehata, Kei Takahashi, Kohei Miyazono, Yoshihiro Hayakawa, Takehiro Sato, Kohsuke Takeda, Isao Naguro, Hidenori Ichijo
Tumor metastasis is the major cause of deaths in cancer patients and is modulated by intertwined stress-responsive signaling cascades. Here we demonstrate that deletion of stress-responsive apoptosis signal-regulating kinase 1 (Ask1) in platelets results in unstable hemostasis and drastic attenuation of tumor lung metastasis, both of which are attributable to platelet dysfunction. Platelet-specific deletion of Ask1 in mice leads to defects in ADP-dependent platelet aggregation, unstable hemostasis and subsequent attenuation of tumor metastasis...
July 28, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28744026/integrin-%C3%AE-3-akt-signaling-contributes-to-platelet-induced-hemangioendothelioma-growth
#8
Rui Gu, Xin Sun, Yijie Chi, Qishuang Zhou, Hongkai Xiang, Dale B Bosco, Xinhe Lai, Caixia Qin, Kwok-Fai So, Yi Ren, Xiao-Ming Chen
Hemangioendothelioma (HE) is a type of angiomatous lesions that features endothelial cell proliferation. Understanding the mechanisms orchestrating HE angiogenesis can provide therapeutic insights. It has been shown that platelets can support normal and malignant endothelial cells during angiogenesis. Using the mouse endothelial-derived EOMA cell line as a model of HE, we explored the regulatory effect of platelets. We found that platelets stimulated EOMA proliferation but did not mitigate apoptosis. Furthermore, direct platelet-EOMA cell contact was required and the proliferation was mediated via integrin β3/Akt signaling in EOMA cells...
July 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28743831/effective-protection-against-acute-respiratory-distress-syndrome-sepsis-injury-by-combined-adipose-derived-mesenchymal-stem-cells-and-preactivated-disaggregated-platelets
#9
Chih-Hung Chen, Yung-Lung Chen, Pei-Hsun Sung, Cheuk-Kwan Sun, Kuan-Hung Chen, Yi-Ling Chen, Tien-Hung Huang, Hung-I Lu, Fan-Yen Lee, Jiunn-Jye Sheu, Sheng-Ying Chung, Mel S Lee, Hon-Kan Yip
This study assessed whether combining adipose-derived mesenchymal stem cells (ADMSC) with preactivated, disaggregated shape-changed platelets (PreD-SCP) was superior to either therapy alone for protecting rat lung from acute respiratory distress syndrome (ARDS) complicated by sepsis. ARDS and sepsis were induced through 100% oxygen inhalation and peritoneal administration of 1.5 mg/kg lipopolysaccharide (LPS), respectively. Adult-male Sprague-Dawley rats (n=40) were randomized into sham-control (SC), ARDS-LPS, ARDS-LPS-ADMSC (1...
July 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28738389/pdgf-promotes-the-warburg-effect-in-pulmonary-arterial-smooth-muscle-cells-via-activation-of-the-pi3k-akt-mtor-hif-1%C3%AE-signaling-pathway
#10
Yunbin Xiao, Hongyan Peng, Chenliang Hong, Zhi Chen, Xicheng Deng, Aiping Wang, Fang Yang, Li Yang, Chen Chen, Xuping Qin
BACKGROUND/AIMS: The enhanced proliferation of pulmonary arterial smooth muscle cells (PASMCs) is a central pathological component in pulmonary arterial hypertension (PAH). Both the Warburg effect and platelet-derived growth factor (PDGF) are involved in the proliferation of PASMCs. However, the mechanism underlying the crosstalk between the Warburg effect and PDGF during PASMC proliferation is still unknown. We hypothesized that PDGF promotes the Warburg effect via activating the phosphatidylinositol 3-kinase (PI3K) signaling pathway and hypoxia-inducible factor 1-α (HIF-1α) in proliferative PASMCs...
July 24, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28737764/paired-related-homeobox-protein-1-regulates-pdgf-induced-chemotaxis-of-hepatic-stellate-cells-in-liver-fibrosis
#11
Jin Gong, Jian Han, Jiayi He, Jingmei Liu, Ping Han, Yunwu Wang, Mengke Li, Dongxiao Li, Xiangming Ding, Zhipeng Du, Jiazhi Liao, Dean Tian
Activation of the platelet-derived growth factor (PDGF)/PDGF beta receptor (PDGFβR) axis has a critical role in liver fibrosis. However, the mechanisms that regulate the PDGF signaling are yet to be elucidated. The present study demonstrates that paired related homeobox protein 1 (Prrx1) is involved in PDGF-dependent hepatic stellate cell (HSCs) migration via modulation of the expression of metalloproteinases MMP2 and MMP9. PDGF elevated the level of Prrx1 through the activation of ERK/Sp1 and PI3K/Akt/Ets1 pathways...
July 24, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28734947/platelet-derived-growth-factor-receptor-alpha-contributes-to-human-hepatic-stellate-cell-proliferation-and-migration
#12
Alexander Kikuchi, Tirthadipa Pradhan-Sundd, Sucha Singh, Shanmugam Nagarajan, Nick Loizos, Satdarshan Monga
Platelet-derived growth factor receptor alpha (PDGFRα), a tyrosine kinase receptor, is up-regulated in hepatic stellate cells (HSCs) during chronic liver injury. HSCs mediate hepatic fibrosis through their activation from a quiescent state partially in response to pro-fibrotic growth factors. HSC activation entails enhanced expression of pro-fibrotic genes, increase in proliferation, and increase in motility, which facilitates migration within the hepatic lobule. We show co-localization of PDGFRα in murine carbon tetrachloride, bile duct ligation (BDL), and 0...
July 19, 2017: American Journal of Pathology
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
#13
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...
September 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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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...
September 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
#20
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
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