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PLCγ2

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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
#1
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...
March 27, 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
#2
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 E 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 sub-clonal, 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 WM and ABC DLBCL cells, and observed re-activation of BTK-PLCγ2-ERK1/2 signaling in the presence of ibrutinib in only the former...
March 1, 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
#3
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
#4
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...
February 7, 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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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...
December 13, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29206177/new-therapeutic-agent-against-arterial-thrombosis-an-iridium-iii-derived-organometallic-compound
#12
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
https://www.readbyqxmd.com/read/29133930/plc%C3%AE-dependent-mtor-signalling-controls-il-7-mediated-early-b-cell-development
#13
Mei Yu, Yuhong Chen, Hu Zeng, Yongwei Zheng, Guoping Fu, Wen Zhu, Ulrich Broeckel, Praful Aggarwal, Amy Turner, Geoffrey Neale, Cliff Guy, Nan Zhu, Hongbo Chi, Renren Wen, Demin Wang
The precise molecular mechanism underlying the regulation of early B cell lymphopoiesis is unclear. The PLCγ signaling pathway is critical for antigen receptor-mediated lymphocyte activation, but its function in cytokine signaling is unknown. Here we show that PLCγ1/PLCγ2 double deficiency in mice blocks early B cell development at the pre-pro-B cell stage and renders B cell progenitors unresponsive to IL-7. PLCγ pathway inhibition blocks IL-7-induced activation of mTOR, but not Stat5. The PLCγ pathway activates mTOR through the DAG/PKC signaling branch, independent of the conventional Akt/TSC/Rheb signaling axis...
November 13, 2017: Nature Communications
https://www.readbyqxmd.com/read/29122990/expression-of-cobll1-encoding-novel-ror1-binding-partner-is-robust-predictor-of-survival-in-chronic-lymphocytic-leukemia
#14
Hana Plešingerová, Pavlína Janovská, Archana Mishra, Lucie Smyčková, Lucie Poppová, Antonín Libra, Karla Plevová, Petra Ovesná, Lenka Radová, Michael Doubek, Šárka Pavlová, Šárka Pospíšilová, Vítězslav Bryja
Chronic lymphocytic leukemia is a disease with upregulated expression of the transmembrane tyrosine-protein kinase ROR1, a member of the Wnt/planar cell polarity pathway. In this study, we identified COBLL1 as a novel interaction partner of ROR1. COBLL1 shows clear bimodal expression with high levels in chronic lymphocytic leukemia patients with mutated IGHV and approximately 30% of chronic lymphocytic leukemia patients with unmutated IGHV. In the remaining 70% of chronic lymphocytic leukemia patients with unmutated IGHV, COBLL1 expression is low...
November 9, 2017: Haematologica
https://www.readbyqxmd.com/read/29047262/current-understanding-of-rank-signaling-in-osteoclast-differentiation-and-maturation
#15
REVIEW
Jin Hee Park, Na Kyung Lee, Soo Young Lee
Osteoclasts are bone-resorbing cells that are derived from hematopoietic precursor cells and require macrophage-colony stimulating factor and receptor activator of nuclear factor-κB ligand (RANKL) for their survival, proliferation, differentiation, and activation. The binding of RANKL to its receptor RANK triggers osteoclast precursors to differentiate into osteoclasts. This process depends on RANKL-RANK signaling, which is temporally regulated by various adaptor proteins and kinases. Here we summarize the current understanding of the mechanisms that regulate RANK signaling during osteoclastogenesis...
October 2017: Molecules and Cells
https://www.readbyqxmd.com/read/28955231/nardosinone-suppresses-rankl-induced-osteoclastogenesis-and-attenuates-lipopolysaccharide-induced-alveolar-bone-resorption
#16
Chenguang Niu, Fei Xiao, Keyong Yuan, XuChen Hu, Wenzhen Lin, Rui Ma, Xiaoling Zhang, Zhengwei Huang
Periodontitis is a chronic inflammatory disease that damages the integrity of the tooth-supporting tissues, known as the periodontium, and comprising the gingiva, periodontal ligament and alveolar bone. In this study, the effects of nardosinone (Nd) on bone were tested in a model of lipopolysaccharide (LPS)-induced alveolar bone loss, and the associated mechanisms were elucidated. Nd effectively suppressed LPS-induced alveolar bone loss and reduced osteoclast (OC) numbers in vivo. Nd suppressed receptor activator of nuclear factor-κB ligand (RANKL)-mediated OC differentiation, bone resorption, and F-actin ring formation in a dose-dependent manner...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28910360/transgelin-2-is-upregulated-on-activated-b-cells-and-expressed-in-hyperplastic-follicles-in-lupus-erythematosus-patients
#17
Kaori Kiso, Hajime Yoshifuji, Takuma Oku, Masaki Hikida, Koji Kitagori, Yoshitaka Hirayama, Toshiki Nakajima, Hironori Haga, Tatsuaki Tsuruyama, Aya Miyagawa-Hayashino
Transgelin-2 (TAGLN2) is an actin-binding protein that controls actin stability and promotes T cell activation. TAGLN2 is also expressed on B-cells but its function in B-cells is unknown. We found that TAGLN2-expressing B-cells were localized in the germinal center (GC) of secondary lymphoid tissues and TAGLN2 mRNA was significantly upregulated after IgM+IgG stimulation in primary human B-cells, suggesting that TAGLN2 was upregulated upon B-cell activation. In support of this, lymph nodes (LNs) from patients with systemic lupus erythematosus (SLE), in which the intense GC activity have been recognized, showed increased TAGLN2 expression in B-cells compared to control LNs...
2017: PloS One
https://www.readbyqxmd.com/read/28878675/inhibition-of-collagen-induced-platelet-aggregation-by-the-secobutanolide-secolincomolide-a-from-lindera-obtusiloba-blume
#18
Sang-Hyuk Jung, Joo-Hui Han, Hyun-Soo Park, Jung-Jin Lee, Seo Young Yang, Young Ho Kim, Kyung-Sun Heo, Chang-Seon Myung
Atherothrombosis is one of the main underlying cause of cardiovascular diseases. In addition to treating atherothrombosis with antithrombotic agents, there is growing interest in the role of natural food products and biologically active ingredients for the prevention and treatment of cardiovascular diseases. This study aimed to investigate the effect of secolincomolide A (3) isolated from Lindera obtusiloba Blume on platelet activity and identify possible signaling pathways. In our study, the antiplatelet activities of 3 were measured by collagen-induced platelet aggregation and serotonin secretion in freshly isolated rabbit platelets...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28842683/a-novel-ruthenium-ii-derived-organometallic-compound-tq-6-potently-inhibits-platelet-aggregation-ex-vivo-and-in-vivo-studies
#19
Chih-Hsuan Hsia, Marappan Velusamy, Joen-Rong Sheu, Themmila Khamrang, Thanasekaran Jayakumar, Wan-Jung Lu, Kuan-Hung Lin, Chao-Chien Chang
Arterial thrombosis plays a key role in cardiovascular diseases. Hence, developing more effective antithrombotic agents is necessary. We designed a ruthenium (II)-derived complex, [Ru(η(6)-cymene)2-(1H-benzoimidazol-2-yl)-quinoline Cl]BF4 (TQ-6), as a new antiplatelet drug. TQ-6 (0.3 µM) exhibited extremely strong inhibitory activity against platelet aggregation, Src, and Syk phosphorylation stimulated by agonists in human platelets. In collagen-activated platelets, TQ-6 also inhibited ATP-release, [Ca(+2)]i, P-selectin expression, FITC-PAC-1 binding, and hydroxyl radical formation, as well as the phosphorylation of phospholipase Cγ2, protein kinase C, mitogen-activated protein kinases, and Akt...
August 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28836860/enhancement-or-inhibition-of-plc%C3%AE-2-expression-in-rat-hepatocytes-by-recombinant-adenoviral-vectors-that-contain-full-length-gene-or-sirna
#20
X G Chen, Y M Liu, Q X Lv, J Ma
We investigated the effects of recombinant adenovirus vectors that overexpress or silence PLCγ2 on the expression of this gene during hepatocyte proliferation. Hepatocytes were isolated, identified by immunofluorescent cytochemical staining and infected by previously constructed Ad-PLCγ2 and Ad-PLCγ2 siRNA1, siRNA2 and siRNA3. Green fluorescent protein (GFP) expression was observed by fluorescence microscopy. Infection percentage was calculated by flow cytometry. mRNA and protein levels of PLCγ2 were detected by quantitative reverse transcription-PCR (qRT-PCR) and western blotting, respectively...
August 24, 2017: Biotechnic & Histochemistry: Official Publication of the Biological Stain Commission
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