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https://www.readbyqxmd.com/read/29890296/ginsenoside-rp3-inhibits-platelet-activation-and-thrombus-formation-by-regulating-mapk-and-cyclic-nucleotide-signaling
#1
Muhammad Irfan, Da Hye Jeong, Hyuk-Woo Kwon, Jung-Hae Shin, Sang-Joon Park, Dongmi Kwak, Tae-Hwan Kim, Dong-Ha Lee, Hwa-Jin Park, Man Hee Rhee
BACKGROUND & PURPOSE: Ginseng (Panax ginseng C.A. Mayer) contains saponin fractions called ginsenosides, which are thought to be the main components responsible for its various pharmacological activities. Ginsenosides have cardioprotective and antiplatelet effects. In the present study, we evaluated the effects of ginsenoside Rp3 (G-Rp3) on platelet function. METHODS: The in vitro effects of G-Rp3 were evaluated on agonist-induced human and rat platelet aggregation, while [Ca2+ ]i mobilization, granule secretion, integrin αIIb β3 activation, and clot retraction were assessed in rat platelets...
June 8, 2018: Vascular Pharmacology
https://www.readbyqxmd.com/read/29883056/tc21-rras2-regulates-gpvi-fcr%C3%AE-mediated-platelet-activation-and-thrombus-stability
#2
Sumalaxmi Janapati, Jeremy Wurtzel, Carol Dangelmaier, Bhanu Kanth Manne, Dheeraj Bhavanasi, John C Kostyak, Soochong Kim, Michael Holinstat, Satya P Kunapuli, Lawrence E Goldfinger
BACKGROUND: Many RAS family small GTPases are expressed in platelets, including RAC, RHOA, RAP, and H-/N-/RRAS1, but most of their signaling and cellular functions remain poorly understood. Like RRAS1, TC21/RRAS2 reverses HRAS-induced suppression of integrin activation in CHO cells. However, a role for TC21 in platelets has not been explored. OBJECTIVES: To determine TC21 expression in platelets, TC21 activation in response to platelet agonists, and roles of TC21 in platelet function in vitro and in vivo thrombosis...
June 8, 2018: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/29870296/gintonin-modulates-platelet-function-and-inhibits-thrombus-formation-via-impaired-glycoprotein-vi-signaling
#3
Muhammad Irfan, Dahye Jeong, Evelyn Saba, Hyuk-Woo Kwon, Jung-Hae Shin, Bo-Ra Jeon, Suk Kim, Sung-Dae Kim, Dong-Ha Lee, Seung-Yeol Nah, Man Hee Rhee
Panax ginseng (P. ginseng), one of the most valuable medicinal plants, is known for its healing and immunobooster properties and has been widely used in folk medicine against cardiovascular diseases, including stroke and heart attack. In this study, we explored the anti-platelet activity of gintonin (a recently discovered non-saponin fraction of ginseng) against agonist-induced platelet activation. In vitro effects of gintonin on agonist-induced human and rat platelet aggregation, granule secretion, integrin αIIb β3 activation, and intracellular calcium ion ([Ca2+ ]i ) mobilization were examined...
June 5, 2018: Platelets
https://www.readbyqxmd.com/read/29867947/-tespa1-deficiency-dampens-thymus-dependent-b-cell-activation-and-attenuates-collagen-induced-arthritis-in-mice
#4
Yunliang Yao, Wei Huang, Xiaoyu Li, Xiawei Li, Jin Qian, Hui Han, Hui Sun, Xiangli An, Linrong Lu, Hongxing Zhao
Thymocyte-expressed, positive selection-associated 1 ( Tespa1 ) plays an important role in both T cell receptor (TCR)-driven thymocyte development and in the FcεRI-mediated activation of mast cells. Herein, we show that lack of Tespa1 does not impair B cell development but dampens the in vitro activation and proliferation of B cells induced by T cell-dependent (TD) antigens, significantly reduces serum antibody concentrations in vivo , and impairs germinal center formation in both aged and TD antigen-immunized mice...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29795134/pharmacological-actions-of-miltirone-in-the-modulation-of-platelet-function
#5
Wei Song, Yuan-Yuan Ma, Shuo Miao, Ru-Ping Yang, Ying Zhu, Dan Shu, Meng Lu, Rong Ma, Zhang-Yin Ming
Salvia miltiorrhiza Bunge contains various active constituents, some of which have been developed as commercially available medicine. Moreover, some other ingredients in Salvia miltiorrhiza play roles in anti-platelet activity. The aim of the present study was to investigate the effects and the underlying mechanism of miltirone, a lipophilic compound of Salvia miltiorrhiza Bunge. The ability of miltirone to modulate platelet function was investigated by a variety of in vitro and in vivo experiments. Platelet aggregation and dense granule secretion induced by various agonists were measured with platelet aggregometer...
May 23, 2018: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/29794149/nlrp3-regulates-platelet-integrin-%C3%AE-iib%C3%AE-3-outside-in-signaling-hemostasis-and-arterial-thrombosis
#6
Jianlin Qiao, Xiaoqing Wu, Qi Luo, Guangyu Wei, Mengdi Xu, Yulu Wu, Yun Liu, Xiaoqian Li, Jie Zi, Wen Ju, Lin Fu, Chong Chen, Qingyun Wu, Shengyun Zhu, Kunming Qi, Depeng Li, Zhenyu Li, Robert K Andrews, Lingyu Zeng, Elizabeth E Gardiner, Kailin Xu
In addition to hemostatic function, platelets play an important role in regulating the inflammatory response. The platelet NLRP3 inflammasome not only promotes IL-1β secretion, but was upregulated during platelet activation and thrombus formation in vitro. However, the role of NLRP3 in platelet function and thrombus formation in vivo remains unclear. In this study, we aimed to investigate the role of NLRP3 in platelet integrin αIIbβ3 signaling transduction. Using NLRP3-/- mice, we showed NLRP3-deficient platelets exhibit no significant differences in expression of the platelet-specific adhesive receptors αIIbβ3 integrin, GPIbα or GPVI, however NLRP3-/- platelets transfused into wild-type mice resulted in prolonged tail-bleeding time and delayed arterial thrombus formation, as well as exhibiting impaired spreading on immobilized fibrinogen and defective clot retraction, concomitant with decreased phosphorylation of c-Src, Syk and PLCγ2 in response to thrombin stimulation...
May 24, 2018: Haematologica
https://www.readbyqxmd.com/read/29733744/dyslipidemia-associated-atherogenic-oxidized-lipids-induce-platelet-hyperactivity-through-phospholipase-c%C3%AE-2-dependent-reactive-oxygen-species-generation
#7
Martin Berger, Katie Wraith, Casey Woodward, Ahmed Aburima, Zaher Raslan, Matthew S Hindle, Julia Moellmann, Maria Febbraio, Khalid M Naseem
Oxidized low-density lipoprotein (oxLDL) and associated oxidized phosphocholine-headgroup phospholipids (oxPCs) activate blood platelets through ligation of the scavenger receptor CD36. Previously, we found that oxLDL stimulated phosphorylation of phospholipase Cγ2 (PLCγ2). However, the functional relevance of PLCγ2 phosphorylation in oxLDL-mediated platelet hyperactivity remained elusive. Here, we set out to explore the functional importance of PLCγ2 in oxLDL-mediated platelet activation using human and genetically modified murine platelets...
May 7, 2018: Platelets
https://www.readbyqxmd.com/read/29695020/significant-hypo-responsiveness-to-gpvi-and-clec-2-agonists-in-pre-term-and-full-term-neonatal-platelets-and-following-immune-thrombocytopenia
#8
Alexander T Hardy, Verónica Palma-Barqueros, Stephanie K Watson, Jean-Daniel Malcor, Johannes A Eble, Elizabeth E Gardiner, José E Blanco, Rafael Guijarro-Campillo, Juan L Delgado, María L Lozano, Raúl Teruel-Montoya, Vicente Vicente, Steve P Watson, José Rivera, Francisca Ferrer-Marín
Neonatal platelets are hypo-reactive to the tyrosine kinase-linked receptor agonist collagen. Here, we have investigated whether the hypo-responsiveness is related to altered levels of glycoprotein VI (GPVI) and integrin α2β1, or to defects in downstream signalling events by comparison to platelet activation by C-type lectin-like receptor 2 (CLEC-2). GPVI and CLEC-2 activate a Src- and Syk-dependent signalling pathway upstream of phospholipase C (PLC) γ2. Phosphorylation of a conserved YxxL sequence known as a (hemi) immunotyrosine-based-activation-motif (ITAM) in both receptors is critical for Syk activation...
June 2018: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/29601810/2-3-dihydroxy-5-methoxybiphenyl-suppresses-fmlp-induced-superoxide-anion-production-and-cathepsin-g-release-by-targeting-the-%C3%AE-subunit-of-g-protein-in-human-neutrophils
#9
Hsiang-Ruei Liao, Ih-Sheng Chen, Fu-Chao Liu, Shinn-Zhi Lin, Ching-Ping Tseng
This study investigates the effect and the underlying mechanism of 2',3-dihydroxy-5-methoxybiphenyl (RIR-2), a lignan extracted from the roots of Rhaphiolepis indica (L.) Lindl. ex Ker var. tashiroi Hayata ex Matsum. & Hayata (Rosaceae), on N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP)-induced respiratory burst and cathepsin G in human neutrophils. Signaling pathways regulated by RIR-2 which modulated fMLP-induced respiratory burst were evaluated by an interaction between β subunit of G-protein (Gβ) with downstream signaling induced by fMLP and by immunoblotting analysis of the downstream targets of Gβ-protein...
June 15, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29496671/btk-cys481ser-drives-ibrutinib-resistance-via-erk1-2-and-protects-btk-wild-type-myd88-mutated-cells-by-a-paracrine-mechanism
#10
Jiaji G Chen, Xia Liu, Manit Munshi, Lian Xu, Nicholas Tsakmaklis, Maria G Demos, Amanda Kofides, Maria Luisa Guerrera, Gloria G Chan, Christopher J Patterson, Kirsten Meid, Joshua Gustine, Toni Dubeau, Patricia Severns, Jorge J Castillo, Zachary R Hunter, Jinhua Wang, Sara J Buhrlage, Nathanael S Gray, Steven P Treon, Guang Yang
Acquired ibrutinib resistance due to BTKCys481 mutations occurs in B-cell malignancies, including those with MYD88 mutations. BTKCys481 mutations are usually subclonal, and their relevance to clinical progression remains unclear. Moreover, the signaling pathways that promote ibrutinib resistance remain to be clarified. We therefore engineered BTKCys481Ser and BTKWT expressing MYD88-mutated Waldenström macroglobulinemia (WM) and activated B-cell (ABC) diffuse large B-cell lymphoma (DLBCL) cells and observed reactivation of BTK-PLCγ2-ERK1/2 signaling in the presence of ibrutinib in only the former...
May 3, 2018: Blood
https://www.readbyqxmd.com/read/29496178/eisenia-bicyclis-brown-alga-modulates-platelet-function-and-inhibits-thrombus-formation-via-impaired-p-2-y-12-receptor-signaling-pathway
#11
Muhammad Irfan, Tae-Hyung Kwon, Bong-Sik Yun, Nyun-Ho Park, Man Hee Rhee
BACKGROUND AND PURPOSE: Sea weeds have been used since ancient times in Asian countries, especially in Korea, Japan, and China, as both edible sea vegetables and traditional medicinal tonics due to their health benefits. Eisenia bicyclis has been studied for anti-allergic and anti-cancer effects; however, its effects on the cardiovascular system, especially on platelet function, are yet to be explored. Therefore, we examined the effect of E. bicyclis on platelet function. STUDY DESIGN AND METHODS: E...
February 1, 2018: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/29436605/novel-iridium-iii-%C3%A2-derived-organometallic-compound-for-the-inhibition-of-human-platelet-activation
#12
Kou-Gi Shyu, Marappan Velusamy, Chih-Wei Hsia, Chih-Hao Yang, Chih-Hsuan Hsia, Duen-Suey Chou, Thanasekaran Jayakumar, Joen-Rong Sheu, Jiun-Yi Li
Since cisplatin achieved clinical success, transition metal platinum (Pt) drugs have been effectively used for the treatment of cancer. Iridium (Ir) compounds are considered to be potential alternatives to Pt compounds, as they possess promising anticancer effects with minor side effects. Platelet activation is associated with the metastasis and progression of cancer, and also with arterial thrombosis. Therefore, it is necessary to develop novel, effective antithrombotic agents. An Ir (III)‑derived complex, [Ir (Cp*) 1‑(2‑pyridyl)‑3‑(3‑methoxyphenyl)imidazo[1,5‑a]pyridine Cl]BF4 (Ir‑3), was developed as a novel antiplatelet drug...
May 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29430764/plc%C3%AE-2-promotes-apoptosis-while-inhibits-proliferation-in-rat-hepatocytes-through-pkcd-jnk-mapk-and-pkcd-p38-mapk-signalling
#13
Xiaoguang Chen, Qiongxia Lv, Jun Ma, Yumei Liu
OBJECTIVES: The PLCG2 (PLCγ2) gene is a member of PLC gene family encoding transmembrane signalling enzymes involved in various biological processes including cell proliferation and apoptosis. Our earlier study indicated that PLCγ2 may be involved in the termination of regeneration of the liver which is mainly composed of hepatocytes, but its exact biological function and molecular mechanism in liver regeneration termination remains unclear. This study aims to examine the role of PLCγ2 in the growth of hepatocytes...
February 11, 2018: Cell Proliferation
https://www.readbyqxmd.com/read/29401630/tetrandrine-attenuates-the-bone-erosion-in-collagen-induced-arthritis-rats-by-inhibiting-osteoclastogenesis-via-spleen-tyrosine-kinase
#14
Yugai Jia, Yumeng Miao, Mengfan Yue, Mei Shu, Zhifeng Wei, Yue Dai
Tetrandrine, a bisbenzylisoquinoline alkaloid, was previously demonstrated to attenuate inflammation and cartilage destruction in the ankles of mice with collagen-induced arthritis (CIA). Here, we explored the underlying mechanism by which tetrandrine prevented arthritis-induced bone erosion by focusing on the differentiation and function of osteoclasts. We found that daily administration of tetrandrine (30 mg/kg) markedly reduced the bone damage and decreased the number of osteoclasts in CIA rats. In vitro, tetrandrine inhibited receptor activator of NF-κB ligand (RANKL)-induced osteoclastogenesis at the early stage and reduced the expressions of osteoclast-related marker genes...
January 30, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29348675/stac2-negatively-regulates-osteoclast-formation-by-targeting-the-rank-signaling-complex
#15
Eutteum Jeong, Han Kyoung Choi, Jin Hee Park, Soo Young Lee
The receptor activator of nuclear factor-κB (RANK) protein activates various protein kinase signaling cascades, including those involving NF-κB, mitogen-activated protein kinase (MAPK), and Bruton tyrosine kinase (Btk)/tyrosine-protein kinase Tec. However, the mechanism underlying the negative regulation of RANK by downstream signaling molecules remains unclear. Here, we report that Src homology 3 domain and cysteine-rich domain-containing protein 2 (STAC2) is a novel RANK ligand-inducible protein that negatively regulates RANK-mediated osteoclast formation...
January 18, 2018: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29324347/design-synthesis-and-biological-evaluation-of-7h-pyrrolo-2-3-d-pyrimidin-4-amine-derivatives-as-selective-btk-inhibitors-with-improved-pharmacokinetic-properties-for-the-treatment-of-rheumatoid-arthritis
#16
Linhong He, Heying Pei, Chufeng Zhang, Mingfeng Shao, Dan Li, Mingli Tang, Taijing Wang, Xiaoxin Chen, Mingli Xiang, Lijuan Chen
Bruton's tyrosine kinase (Btk) is a Tec family kinase with a well-defined role in the B cell receptor (BCR) and Fcγ receptor (FcR) signaling pathways, which makes it a uniquely attractive target for the treatment of autoimmune diseases, such as rheumatoid arthritis (RA). We reported a series of compounds bearing 7H-pyrrolo [2,3-d]pyrimidin-4-amine scaffold that potently inhibited Btk in vitro. Analysis of the structure-activity relationships (SAR) and drug-like profiles led to the discovery of the optimal compound B16...
February 10, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29295843/gpvi-signaling-is-compromised-in-newly-formed-platelets-after-acute-thrombocytopenia-in-mice
#17
Shuchi Gupta, Deya Cherpokova, Markus Spindler, Martina Morowski, Markus Bender, Bernhard Nieswandt
At sites of vascular injury, exposed subendothelial collagens trigger platelet activation and thrombus formation by interacting with the immunoreceptor tyrosine-based activation motif (ITAM)-coupled glycoprotein VI (GPVI) on the platelet surface. Platelets are derived from the cytoplasm of megakaryocytes (MKs), which extend large proplatelets into bone marrow (BM) sinusoids that are then released into the bloodstream, where final platelet sizing and maturation occurs. The mechanisms that prevent activation of MKs and forming proplatelets in the collagen-rich BM environment remain largely elusive...
March 8, 2018: Blood
https://www.readbyqxmd.com/read/29258493/antiplatelet-mechanism-of-an-herbal-mixture-prepared-from-the-extracts-of-phyllostachys-pubescens-leaves-and-prunus-mume-fruits
#18
Eunjung Son, Seung-Hyung Kim, Won-Kyung Yang, Dong-Seon Kim, Jimin Cha
BACKGROUND: Bamboo (Phyllostachys pubescens) leaves and Japanese apricot (Mume fructus) fruit are traditionally recognized to be safe herbs broadly used for food and medicinal purposes in Southeast Asia. Our group previously explored their antiplatelet effects. This study was designed to confirm inhibition effects of PM21 (a 2:1 mixture of bamboo leaf extract and Japanese apricot fruit extract) on platelet aggregation and evaluate its potency to use as an herbal remedy to prevent and/or treat the diseases caused by platelet aggregation and thrombus formation...
December 19, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/29236324/silencing-of-phospholipase-c-gamma-2-promotes-proliferation-of-rat-hepatocytes-in-vitro
#19
Xiaoguang Chen, Xuemin Zhu, Yumei Liu, Qiongxia Lv, Jun Ma
The management of hepatic failure is undoubtedly difficult, and poor results have led to the search for novel therapeutic approaches. Nowadays, anti-apoptotic gene therapy is considered as an ideal approach. It has been proved that phospholipase Cγ2 (PLCγ2) is involved in the apoptosis of immune cells and tumor cells; however, whether this gene is related to hepatocyte death is still unclear. This study examined the role of PLCγ2 by inhibiting its expression in rat hepatocytes with siRNA. We also further analyzed the cellular mechanism by which the expression inhibition of PLCγ2 induces cell death...
May 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29206177/new-therapeutic-agent-against-arterial-thrombosis-an-iridium-iii-derived-organometallic-compound
#20
Chih-Wei Hsia, Marappan Velusamy, Jeng-Ting Tsao, Chih-Hsuan Hsia, Duen-Suey Chou, Thanasekaran Jayakumar, Lin-Wen Lee, Jiun-Yi Li, Joen-Rong Sheu
Platelet activation plays a major role in cardio and cerebrovascular diseases, and cancer progression. Disruption of platelet activation represents an attractive therapeutic target for reducing the bidirectional cross talk between platelets and tumor cells. Platinum (Pt) compounds have been used for treating cancer. Hence, replacing Pt with iridium (Ir) is considered a potential alternative. We recently developed an Ir(III)-derived complex, [Ir(Cp*)1-(2-pyridyl)-3-(2-hydroxyphenyl)imidazo[1,5-a]pyridine Cl]BF₄ (Ir-11), which exhibited strong antiplatelet activity; hence, we assessed the therapeutic potential of Ir-11 against arterial thrombosis...
December 5, 2017: International Journal of Molecular Sciences
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