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https://www.readbyqxmd.com/read/29470443/structure-antiplatelet-activity-relationships-of-novel-ruthenium-ii-complexes-investigation-of-its-molecular-targets
#1
Chih-Hsuan Hsia, Thanasekaran Jayakumar, Joen-Rong Sheu, Shin-Yi Tsao, Marappan Velusamy, Chih-Wei Hsia, Duen-Suey Chou, Chao-Chien Chang, Chi-Li Chung, Themmila Khamrang, Kao-Chang Lin
The regulation of platelet function by pharmacological agents that modulate platelet signaling has proven to be a positive approach to the prevention of thrombosis. Ruthenium complexes are fascinating for the development of new drugs, as they possess numerous chemical and biological properties. The present study aims to evaluate the structure-activity relationship (SAR) of newly synthesized ruthenium (II) complexes, TQ-1, TQ-2 and TQ-3 in agonists-induced washed human platelets. Silica gel column chromatography, aggregometry, immunoblotting, NMR, and X-ray analyses were performed in this study...
February 22, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29453318/integration-of-distinct-shca-signaling-complexes-promotes-breast-tumor-growth-and-tyrosine-kinase-inhibitor-resistance
#2
Jacqueline R Ha, Ryuhjin Ahn, Harvey W Smith, Valerie Sabourin, Steven Hėbert, Eduardo Cepeda Cañedo, Young Kyuen Im, Claudia Kleinman, William J Muller, Josie Ursini-Siegel
The commonality between most phospho-tyrosine signaling networks is their shared use of adaptor proteins to transduce mitogenic signals. ShcA (SHC1) is one such adaptor protein that employs two phospho-tyrosine binding domains (PTB and SH2) and key phospho-tyrosine residues to promote mammary tumorigenesis. Receptor tyrosine kinases (RTKs), such as ErbB2, engage the ShcA PTB domain to promote breast tumorigenesis by engaging Grb2 downstream of the ShcA tyrosine phosphorylation sites to activate AKT/mTOR signaling...
February 16, 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29435078/gene-expression-analyses-associated-with-malignant-phenotypes-of-metastatic-sub-clones-derived-from-a-mouse-oral-squamous-cell-carcinoma-sq-1979-cell-line
#3
Mitsutaka Adachi, Masako Mizuno-Kamiya, Eiji Takayama, Harumi Kawaki, Toshihiro Inagaki, Shigeki Sumi, Masayuki Motohashi, Yasunori Muramatsu, Shin-Ichiro Sumitomo, Michio Shikimori, Yutaka Yamazaki, Nobuo Kondoh
To elucidate the genetic events that occur during the development of OSCC, the present study established a model of oral malignancy using a mouse oral squamous cell carcinoma (OSCC) Sq-1979 cell line. Sq-1979 cells were implanted into syngeneic C3H mice. Subsequently, 233 cells and metastatic sub-clones (L cells) from primary OSCC, as well as the metastasized lymph node tissues of Sq-1979-implanted mice were established. Compared with parental Sq-1979 and 233 cells, the majority of L cells exhibited a higher proliferation rate and transplantability, and conferred a lower survival rate on the implanted mice...
March 2018: Oncology Letters
https://www.readbyqxmd.com/read/29434909/fyn-knockdown-inhibits-migration-and-invasion-in-cholangiocarcinoma-through-the-activated-ampk-mtor-signaling-pathway
#4
Shao-Cheng Lyu, Dong-Dong Han, Xian-Liang Li, Jun Ma, Qiao Wu, Hong-Meng Dong, Chun Bai, Qiang He
Cholangiocarcinoma (CCA) is a rare and fatal tumor. In previous decades, there has been a steady increase in the incidence and mortality rates of this tumor worldwide. Metastasis is regarded as the major factor that contributes to poor prognosis in CCA patients. Studies therefore aim to develop novel therapeutic targets to control CCA metastasis. Fyn is known to enhance expression and promote metastasis in various cancers, including pancreatic cancer, prostate cancer and colorectal cancer. However, the exact function and mechanism of Fyn in CCA metastasis remains unclear...
February 2018: Oncology Letters
https://www.readbyqxmd.com/read/29432180/piezo2-channel-regulates-rhoa-and-actin-cytoskeleton-to-promote-cell-mechanobiological-responses
#5
Carlos Pardo-Pastor, Fanny Rubio-Moscardo, Marina Vogel-González, Selma A Serra, Alexandros Afthinos, Sanela Mrkonjic, Olivier Destaing, Juan F Abenza, José M Fernández-Fernández, Xavier Trepat, Corinne Albiges-Rizo, Konstantinos Konstantopoulos, Miguel A Valverde
Actin polymerization and assembly into stress fibers (SFs) is central to many cellular processes. However, how SFs form in response to the mechanical interaction of cells with their environment is not fully understood. Here we have identified Piezo2 mechanosensitive cationic channel as a transducer of environmental physical cues into mechanobiological responses. Piezo2 is needed by brain metastatic cells from breast cancer (MDA-MB-231-BrM2) to probe their physical environment as they anchor and pull on their surroundings or when confronted with confined migration through narrow pores...
February 5, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29413525/synaptotoxic-signaling-by-amyloid-beta-oligomers-in-alzheimer-s-disease-through-prion-protein-and-mglur5
#6
A Harrison Brody, Stephen M Strittmatter
Alzheimer's disease (AD) represents an impending global health crisis, yet the complexity of AD pathophysiology has so far precluded the development of any interventions to successfully slow or halt AD progression. It is clear that accumulation of Amyloid-beta (Aβ) peptide triggers progressive synapse loss to cause AD symptoms. Once initiated by Aβ, disease progression is complicated and accelerated by inflammation and by tau pathology. The recognition that Aβ peptide assumes multiple distinct states and that soluble oligomeric species (Aβo) are critical for synaptic damage is central to molecular understanding of AD...
2018: Advances in Pharmacology
https://www.readbyqxmd.com/read/29390798/deciphering-complex-dynamics-of-water-counteraction-around-secondary-structural-elements-of-allosteric-protein-complex-case-study-of-sap-slam-system-in-signal-transduction-cascade
#7
Sudipta Samanta, Sanchita Mukherjee
The first hydration shell of a protein exhibits heterogeneous behavior owing to several attributes, majorly local polarity and structural flexibility as revealed by solvation dynamics of secondary structural elements. We attempt to recognize the change in complex water counteraction generated due to substantial alteration in flexibility during protein complex formation. The investigation is carried out with the signaling lymphocytic activation molecule (SLAM) family of receptors, expressed by an array of immune cells, and interacting with SLAM-associated protein (SAP), composed of one SH2 domain...
January 28, 2018: Journal of Chemical Physics
https://www.readbyqxmd.com/read/29374752/photocarcinogenesis-and-skin-cancer-prevention-strategies-an-update
#8
REVIEW
Marie Christine Martens, Christina Seebode, Janin Lehmann, Steffen Emmert
UV radiation is acknowledged as the primary cause of photocarcinogenesis and therefore contributes to the development of skin cancer entities such as squamous cell carcinoma (SCC), basal cell carcinoma (BCC), and melanoma. Typical DNA photoproducts and indirect DNA damage caused by reactive oxygen species are the result of UV radiation. UV-induced DNA damage is repaired by nucleotide excision repair, which consequently counteracts the development of mutations and skin carcinogenesis. Tumour-suppressor genes are inactivated by mutation and growth-promoting pathways are activated leading to disruption of cell-cycle progression...
February 2018: Anticancer Research
https://www.readbyqxmd.com/read/29366662/cd45-in-human-physiology-and-clinical-medicine
#9
REVIEW
Andreas Rheinländer, Burkhart Schraven, Ursula Bommhardt
CD45 is an evolutionary highly conserved receptor protein tyrosine phosphatase exclusively expressed on all nucleated cells of the hematopoietic system. It is characterized by the expression of several isoforms, specific to a certain cell type and the developmental or activation status of the cell. CD45 is one of the key players in the initiation of T cell receptor signaling by controlling the activation of the Scr family protein-tyrosine kinases Lck and Fyn. CD45 defiency results in T- and B-lymphocyte dysfunction in the form of severe combined immune deficiency...
January 20, 2018: Immunology Letters
https://www.readbyqxmd.com/read/29353218/sulforaphane-prevents-angiotensin-ii-induced-cardiomyopathy-by-activation-of-nrf2-via-stimulating-the-akt-gsk-3%C3%A3-fyn-pathway
#10
Ying Xin, Yang Bai, Xin Jiang, Shanshan Zhou, Yuehui Wang, Kupper A Wintergerst, Taixing Cui, Honglei Ji, Yi Tan, Lu Cai
AIMS: Activation of nuclear factor erythroid 2-related factor 2 (Nrf2) by sulforaphane (SFN) protects from, and deletion of the Nrf2 gene exaggerates, diabetic cardiomyopathy. Angiotensin II (Ang II) plays a critical role in the development of diabetic cardiomyopathy. Therefore, whether SFN prevents Ang II-induced cardiomyopathy through activation of Nrf2 was examined using wild-type, global deletion of Nrf2 gene (Nrf2-KO) and cardiomyocyte-specific overexpression of Nrf2 gene (Nrf2-TG) mice...
January 2, 2018: Redox Biology
https://www.readbyqxmd.com/read/29348886/frk-inhibits-breast-cancer-cell-migration-and-invasion-by-suppressing-epithelial-mesenchymal-transition
#11
Yetunde Ogunbolude, Chenlu Dai, Edward T Bagu, Raghuveera Kumar Goel, Sayem Miah, Joshua MacAusland-Berg, Chi Ying Ng, Rajni Chibbar, Scott Napper, Leda Raptis, Frederick Vizeacoumar, Franco Vizeacoumar, Keith Bonham, Kiven Erique Lukong
The human fyn-related kinase (FRK) is a non-receptor tyrosine kinase known to have tumor suppressor activity in breast cancer cells. However, its mechanism of action has not been fully characterized. We generated FRK-stable MDA-MB-231 breast cancer cell lines and analyzed the effect on cell proliferation, migration, and invasiveness. We also used kinome analysis to identify potential FRK-regulated signaling pathways. We employed both immunoblotting and RT-PCR to identify/validate FRK-regulated targets (proteins and genes) in these cells...
December 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29348460/fyn-promotes-mesenchymal-phenotypes-of-basal-type-breast-cancer-cells-through-stat5-notch2-signaling-node
#12
Ga-Hang Lee, Ki-Chun Yoo, Yoojeong An, Hae-June Lee, Minyoung Lee, Nizam Uddin, Min-Jung Kim, In-Gyu Kim, Yongjoon Suh, Su-Jae Lee
Basal type breast cancer is the most aggressive and has mesenchymal features with a high metastatic ability. However, the signaling node that determines the basal type features in breast cancer remains obscure. Here, we report that FYN among SRC family kinases is required for the maintenance of basal type breast cancer subtype. Importantly, FYN enhanced NOTCH2 activation in basal type breast cancer cells through STAT5-mediated upregulation of Jagged-1 and DLL4 NOTCH ligands, thereby contributed to mesenchymal phenotypes...
January 19, 2018: Oncogene
https://www.readbyqxmd.com/read/29334762/altered-redox-state-modulates-endothelial-kca2-3-and-kca3-1-levels-in-normal-pregnancy-and-preeclampsia
#13
Shinkyu Choi, Ji Aee Kim, Hai-Yan Li, Sae-Jin Lee, Ye Seon Seok, Tae Hun Kim, Ki-Hwan Han, Mi Hye Park, Geum Joon Cho, Suk Hyo Suh
AIMS: Altered redox state has been related to the development of normal pregnancy (NP) and preeclampsia (PE). Endothelial KCa2.3 and KCa3.1 (KCas) play an important role in vasodilation, and KCas levels are affected by oxidative stress. We investigated the mechanisms of oxidative stress-mediated KCas expression modulation during NP and PE. RESULTS: Human uterine microvascular endothelial cells were incubated in serum from normal non-pregnant women (n=13) and women with NP (n=24) or PE (n=15), or in VEGF, oxidized low-density lipoprotein (ox-LDL), progesterone, or estradiol-17-containing medium for 24 hours...
January 15, 2018: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/29321689/analysis-of-combined-transcriptomes-identifies-gene-modules-that-differentially-respond-to-pathogenic-stimulation-of-vascular-smooth-muscle-and-endothelial-cells
#14
Xiaokang Pan, Bowen Wang, Tiezheng Yuan, Mengxue Zhang, K Craig Kent, Lian-Wang Guo
Smooth muscle cells (SMCs) and endothelial cells (ECs) are vital cell types composing the vascular medial wall and the atheroprotective inner lining, respectively. Current treatments for cardiovascular disease inhibit SMC hyperplasia but compromise EC integrity, predisposing patients to thrombosis. Therapeutics targeting SMCs without collateral damage to ECs are highly desirable. However, differential (SMC versus EC) disease-associated regulations remain poorly defined. We conducted RNA-seq experiments to investigate SMC-versus-EC differential transcriptomic dynamics, following treatment of human primary SMCs and ECs with TNFα or IL-1β, both established inducers of SMC hyperplasia and EC dysfunction...
January 10, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29318780/the-synergistic-role-of-atp-dependent-drug-efflux-pump-and-focal-adhesion-signaling-pathways-in-vinorelbine-resistance-in-lung-cancer
#15
Takao Nakanishi, Toshi Menju, Shigeto Nishikawa, Koji Takahashi, Ryo Miyata, Kei Shikuma, Terumasa Sowa, Naoto Imamura, Masatsugu Hamaji, Hideki Motoyama, Kyoko Hijiya, Akihiro Aoyama, Toshihiko Sato, Toyofumi F Chen-Yoshikawa, Makoto Sonobe, Hiroshi Date
The vinorelbine (VRB) plus cisplatin regimen is widely used to treat non-small cell lung cancer (NSCLC), but its cure rate is poor. Drug resistance is the primary driver of chemotherapeutic failure, and the causes of resistance remain unclear. By focusing on the focal adhesion (FA) pathway, we have highlighted a signaling pathway that promotes VRB resistance in lung cancer cells. First, we established VRB-resistant (VR) lung cancer cells (NCI-H1299 and A549) and examined its transcriptional changes, protein expressions, and activations...
January 10, 2018: Cancer Medicine
https://www.readbyqxmd.com/read/29277769/%C3%AE-v%C3%AE-6-fyn-kinase-promotes-epithelial-phenotype-in-syf-cells
#16
Casey Lee, Daniel M Ramos
The 5-year survival rate for patients with oral cancer remains at 50%, in large part due the high rate of post-treatment recurrence. In this study, we transfected epithelial-specific integrin αvβ6 and Fyn-kinase, a member of the Src-family kinases, into embryonic murine fibroblasts. In oral cancer, expression of αvβ6 is neo-expressed. Using a variety of in vitro assays, including cell migration and multicellular spheroid formation, we determined that these embryonic fibroblasts expressing αvβ6 and Fyn-kinase were able to acquire an epithelial phenotype...
January 2018: Anticancer Research
https://www.readbyqxmd.com/read/29241709/regulation-of-pleiotrophin-and-fyn-in-the-striatum-of-rats-undergoing-l-dopa-induced-dyskinesia
#17
Gimena Gomez, Mariano D Saborido, María A Bernardi, Oscar S Gershanik, Irene R Taravini, Juan E Ferrario
L-DOPA is the gold standard pharmacological therapy for symptomatic treatment of Parkinson's disease (PD), however, its long-term use is associated with the emergence of L-DOPA-induced dyskinesia (LID). Understanding the underlying molecular mechanisms of LID is crucial for the development of newer and more effective therapeutic approaches. In previous publications, we have shown that Pleiotrophin (PTN), a developmentally regulated trophic factor, is up-regulated by L-DOPA in the striatum of dopamine denervated rats...
December 11, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/29224116/chemical-shift-assignments-of-the-partially-deuterated-fyn-sh2-sh3-domain
#18
Fabien Kieken, Karine Loth, Nico van Nuland, Peter Tompa, Tom Lenaerts
Src Homology 2 and 3 (SH2 and SH3) are two key protein interaction modules involved in regulating the activity of many proteins such as tyrosine kinases and phosphatases by respective recognition of phosphotyrosine and proline-rich regions. In the Src family kinases, the inactive state of the protein is the direct result of the interaction of the SH2 and the SH3 domain with intra-molecular regions, leading to a closed structure incompetent with substrate modification. Here, we report the 1H, 15N and 13C backbone- and side-chain chemical shift assignments of the partially deuterated Fyn SH3-SH2 domain and structural differences between tandem and single domains...
December 9, 2017: Biomolecular NMR Assignments
https://www.readbyqxmd.com/read/29222871/myelin-extracellular-leaflet-compaction-requires-apolipoprotein-d-membrane-management-to-optimize-lysosomal-dependent-recycling-and-glycocalyx-removal
#19
Nadia García-Mateo, Raquel Pascua-Maestro, Alberto Pérez-Castellanos, Concepción Lillo, Diego Sanchez, Maria D Ganfornina
To compact the extracellular sides of myelin, an important transition must take place: from membrane sliding, while building the wraps, to membrane adhesion and water exclusion. Removal of the negatively charged glycocalyx becomes the limiting factor in such transition. What is required to initiate this membrane-zipping process? Knocking-out the Lipocalin Apolipoprotein D (ApoD), essential for lysosomal functional integrity in glial cells, results in a specific defect in myelin extracellular leaflet compaction in peripheral and central nervous system, which results in reduced conduction velocity and suboptimal behavioral outputs: motor learning is compromised...
December 9, 2017: Glia
https://www.readbyqxmd.com/read/29200667/davallia-mariesii-moore-improves-fc%C3%AE%C2%B5ri-mediated-allergic-responses-in-the-rat-basophilic-leukemia-mast-cell-line-rbl-2h3-and-passive-cutaneous-anaphylaxis-in-mice
#20
Hyun Ju Do, Tae Woo Oh, Ju Hye Yang, Kwang Il Park, Jin Yeul Ma
Davallia mariesii Moore (Drynaria rhizome extract (DRE)) is widely known for its efficacy in treating inflammation, arteriosclerosis, and bone injuries. This study evaluated whether treatment with DRE inhibited FcɛRI-mediated allergic responses in the RBL-2H3 mast cells and investigated the early- and late-phase mechanisms by which DRE exerts its antiallergic effects. IgE anti-DNP/DNP-HSA-sensitized RBL-2H3 mast cells were tested for cytotoxicity to DRE, followed by the assessment of β-hexosaminidase release...
2017: Mediators of Inflammation
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