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https://www.readbyqxmd.com/read/29793021/phosphoinositide-3-kinase-p110%C3%AE-negatively-regulates-thrombopoietin-mediated-platelet-activation-and-thrombus-formation
#1
T A Blair, S F Moore, T G Walsh, J L Hutchinson, T N Durrant, K E Anderson, A W Poole, I Hers
Phosphoinositide 3-kinase (PI3K) plays an important role in platelet function and contributes to platelet hyperreactivity induced by elevated levels of circulating peptide hormones, including thrombopoietin (TPO). Previous work established an important role for the PI3K isoform; p110β in platelet function, however the role of p110α is still largely unexplored. Here we sought to investigate the role of p110α in TPO-mediated hyperactivity by using a conditional p110α knockout (KO) murine model in conjunction with platelet functional assays...
May 21, 2018: Cellular Signalling
https://www.readbyqxmd.com/read/29792731/apr3-modulates-oxidative-stress-and-mitochondrial-function-in-arpe-19-cells
#2
Yuan Li, Xuan Zou, Jing Gao, Ke Cao, Zhihui Feng, Jiankang Liu
Impairment of retinal pigment epithelial (RPE) cells is considered a key contributor to the development of age-related macular degeneration. Apoptosis-related protein 3 (APR3) was recently discovered after treatment with all- trans retinoic acid, a pivotal molecule in RPE cells. However, the function of APR3 remains poorly understood. In the present study, we found that APR3 could interact with nuclear factor (erythroid-derived 2)-like 2, which is a regulator of phase II enzymes, and that knockdown of APR3 promoted nuclear factor (erythroid-derived 2)-like 2 nuclear translocation and activated expression of phase II enzymes, which was accompanied by improved redox status and mitochondrial activity...
May 24, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29792173/impact-of-growth-ph-and-glucose-concentrations-on-the-cody-regulatory-network-in-streptococcus-salivarius
#3
Jianing Geng, Szu-Chuan Huang, Yueh-Ying Chen, Cheng-Hsun Chiu, Songnian Hu, Yi-Ywan M Chen
BACKGROUND: Streptococcus salivarius is an abundant isolate of the human oral microbiota. Since both pH and glucose availability fluctuate frequently in the oral cavity, the goal of this study was to investigate regulation by CodY, a conserved pleiotropic regulator of Gram positive bacteria, in response to these two signals. The chemostat culture system was employed to precisely control the growth parameters, and the transcriptomes of wild-type S. salivarius 57.I and its CodY-null derivative (ΔcodY) grown at pH 7 and 5...
May 23, 2018: BMC Genomics
https://www.readbyqxmd.com/read/29792156/design-synthesis-and-biological-evaluation-of-1h-1-2-3-triazole-linked-1h%C3%A2-dibenzo-b-h-xanthenes-as-inductors-of-ros-mediated-apoptosis-in-the-breast-cancer-cell-line-mcf-7
#4
Carolina S Bortolot, Luana da S M Forezi, Roberta K F Marra, Marcelo I P Reis, Barbara V F E Sa, Ricardo Imbroisi Filho, Zeinab Ghasemishahrestani, Mauro Sola-Penna, Patricia Zancan, Vitor F Ferreira, Fernando de C da Silva
BACKGROUND: Low molecular weight 1,2,3-triazoles and naphthoquinones are endowed with various types of biological activity, such as against cancer, HIV and bacteria. However, in some cases, the conjugation of these two nuclei considerably increases their biological activities Objective: In this work, we decided to study the synthesis and screening of bis-naphthoquinones and xanthenes tethered to 1,2,3-triazoles against cancer cell lines, specifically the human breast cancer cell line MCF-7...
May 23, 2018: Medicinal Chemistry
https://www.readbyqxmd.com/read/29792023/fern-9-11-ene-2%C3%AE-3%C3%AE-diol-action-on-insulin-secretion-in-hyperglycemic-conditions
#5
Allisson Jhonatan Gomes Castro, Luisa Helena Cazarolli, Gabrielle Da Luz, Delsi Altenhofen, Hemily Batista Da Silva, Francieli Kanumfre Carvalho, Moacir Geraldo Pizzolatti, Fátima Rmb Silva
The objective of this study was to investigate the effect and the mechanism of action of fernenediol as insulin secretagogue. Wistar rats were treated with 0.1; 1 and 10 mg/kg fernenediol and then induced hyperglycemia by oral glucose. The glycaemia, insulin, LDH, calcium and hepatic glycogen were analyzed. Considering the intestine and pancreas as targets for the triterpene action, the duodenum was used to verify the influence of fernenediol on intestinal glycosidases. Additionally, pancreatic islets were used for studies of 14 C-deoxyglucose uptake and influx of 45 Ca2+ in hyperglycemic medium with/without fernenediol in the presence/absence of an inhibitor/activator of KATP channels, glibenclamide, diazoxide, nifedipine, calcium chelator (BAPTA- AM) and H-89 and ST the inhibitors of the PKA and PKC enzymes...
May 24, 2018: Biochemistry
https://www.readbyqxmd.com/read/29791843/cell-cycle-regulation-of-dynamic-chromosome-association-of-the-condensin-complex
#6
Rahul Thadani, Julia Kamenz, Sebastian Heeger, Sofía Muñoz, Frank Uhlmann
Eukaryotic cells inherit their genomes in the form of chromosomes, which are formed from the compaction of interphase chromatin by the condensin complex. Condensin is a member of the structural maintenance of chromosomes (SMC) family of ATPases, large ring-shaped protein assemblies that entrap DNA to establish chromosomal interactions. Here, we use the budding yeast Saccharomyces cerevisiae to dissect the role of the condensin ATPase and its relationship with cell-cycle-regulated chromosome binding dynamics...
May 22, 2018: Cell Reports
https://www.readbyqxmd.com/read/29791754/atp-triggers-a-robust-intracellular-ca-2-mediated-signalling-pathway-in-human-synovial-fibroblasts
#7
Kondo C, R B Clark, T Y Kim, Belke D, Banderali U, R T Szerencsei, A H Jalloul, P P M Schnetkamp, Spitzer Kw, Giles Wr
NEW FINDINGS: What is the central question of this study? In human articular joints, the synovial fibroblast HSF cell population has essential functions including secretion of lubricants. We address some remaining questions concerning activation-secretion coupling by characterizing the main [Ca2+ ]i signalling pathways activated by ATP. What is the main finding and its importance? In HSF ATP acts through a linked G-protein (Gq ) and phospholipase C signalling mechanisms to produce IP-3 which markedly enhances release of Ca2+ from the endoplasmic reticulum...
May 23, 2018: Experimental Physiology
https://www.readbyqxmd.com/read/29790985/the-way-is-the-goal-how-seca-transports-proteins-across-the-cytoplasmic-membrane-in-bacteria
#8
Tamar Cranford-Smith, Damon Huber
In bacteria, translocation of most soluble secreted proteins (and outer membrane proteins in Gram-negative bacteria) across the cytoplasmic membrane by the Sec machinery is mediated by the essential ATPase SecA. At its core, this machinery consists of SecA and the integral membrane proteins SecYEG, which form a protein conducting channel in the membrane. Proteins are recognised by the Sec machinery by virtue of an internally encoded targeting signal, which usually takes the form of an N-terminal signal sequence...
June 1, 2018: FEMS Microbiology Letters
https://www.readbyqxmd.com/read/29790984/co-translational-protein-targeting-in-bacteria
#9
Ruth Steinberg, Lara Knüpffer, Andrea Origi, Rossella Asti, Hans-Georg Koch
About 30% of all bacterial proteins execute their function outside of the cytosol and have to be transported into or across the cytoplasmic membrane. Bacteria use multiple protein transport systems in parallel, but the majority of proteins engage two distinct targeting systems. One is the co-translational targeting by two universally conserved GTPases, the signal recognition particle (SRP) and its receptor FtsY, which deliver inner membrane proteins to either the SecYEG translocon or the YidC insertase for membrane insertion...
June 1, 2018: FEMS Microbiology Letters
https://www.readbyqxmd.com/read/29790837/modulation-of-spinal-motor-networks-by-astrocyte-derived-adenosine-is-dependent-on-d1-like-dopamine-receptor-signalling
#10
David Acton, Matthew J Broadhead, Gareth Brian Miles
Astrocytes modulate many neuronal networks, including spinal networks responsible for the generation of locomotor behaviour. Astrocytic modulation of spinal motor circuits involves release of ATP from astrocytes, hydrolysation of ATP to adenosine, and subsequent activation of neuronal A1 adenosine receptors (A1Rs). The net effect of this pathway is a reduction in the frequency of locomotor-related activity. Recently, it was proposed that A1Rs modulate burst frequency by blocking the D1-like dopamine receptor (D1LR) signalling pathway; however, adenosine also modulates ventral horn circuits by dopamine-independent pathways...
May 23, 2018: Journal of Neurophysiology
https://www.readbyqxmd.com/read/29790294/jak-stat-blockade-alters-synovial-bioenergetics-mitochondrial-function-and-pro-inflammatory-mediators-in-rheumatoid-arthritis
#11
Trudy McGarry, Carl Orr, Sarah Wade, Monika Biniecka, Siobhan Wade, Lorna Gallagher, Candice Low, Douglas J Veale, Ursula Fearon
OBJECTIVE: To examine the effect of tofacitinib on metabolic activity, mitochondrial function and pro-inflammatory mechanisms in Rheumatoid Arthritis. METHODS: Ex-vivo RA synovial explants and primary RA synovial fibroblasts (RAFLS) were cultured with tofacitinib (1μM). RAFLS bioenergetics was assessed using the XF24-Flux-analyser, and key metabolic genes by real-time PCR. Mitochondrial function was assessed using specific cell fluorescent probes and by mitochondrial gene arrays...
May 23, 2018: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/29790164/purinergic-receptor-stimulation-induces-calcium-oscillations-and-smooth-muscle-contraction-in-small-pulmonary-veins
#12
Mauricio Henriquez, Marcelo Fonseca, Jose F Perez-Zoghbi
KEY POINTS: We investigated the excitation-contraction coupling mechanisms in small pulmonary veins (SPVs) in rat precision-cut lung slices. We found that SPVs contract strongly and reversibly in response to extracellular ATP and other vasoconstrictors, including angiotensin-II and endothelin-1. ATP-induced vasoconstriction in SPVs was associated with the stimulation of purinergic P2Y2 receptors in vascular smooth muscle cell, activation of phospholipase C-β and the generation of intracellular Ca2+ oscillations mediated by cyclic Ca2+ release events via the inositol 1,4,5-trisphosphate receptor...
May 23, 2018: Journal of Physiology
https://www.readbyqxmd.com/read/29790111/potential-of-the-dual-mtor-kinase-inhibitor-azd2014-to-overcome-paclitaxel-resistance-in-anaplastic-thyroid-carcinoma
#13
Zorica Milošević, Jasna Banković, Jelena Dinić, Chrisiida Tsimplouli, Evangelia Sereti, Miodrag Dragoj, Verica Paunović, Zorka Milovanović, Marija Stepanović, Nikola Tanić, Kostantinos Dimas, Milica Pešić
PURPOSE: Anaplastic thyroid carcinoma (ATC) is an aggressive, chemo-resistant malignancy. Chemo-resistance is often associated with changes in activity of the RAS/MAPK/ERK and PI3K/AKT/mTOR pathways and/or a high expression of ATP binding cassette (ABC) transporters, such as P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP). To assess the therapeutic efficacy in ATC of a combination of the dual mTOR kinase inhibitor vistusertib (AZD2014) and paclitaxel (PTX), we generated a new cell line (Rho-) via the selection of human thyroid carcinoma 8505C cells that exhibit a low accumulation of rhodamine 123, which serves as a P-gp and BCRP substrate...
May 22, 2018: Cellular Oncology (Dordrecht)
https://www.readbyqxmd.com/read/29790043/antimycin-a-inhibits-cytochrome-b-559-mediated-cyclic-electron-flow-within-photosystem-ii
#14
Daisuke Takagi, Kentaro Ifuku, Taishi Nishimura, Chikahiro Miyake
The light reactions of photosynthesis are known to comprise both linear and cyclic electron flow in order to convert light energy into chemical energy in the form of NADPH and ATP. Antimycin A (AA) has been proposed as an inhibitor of ferredoxin-dependent cyclic electron flow around photosystem I (CEF-PSI) in photosynthesis research. However, its precise inhibitory mechanism and target site had not been elucidated yet. Here we show that AA inhibits the cyclic (alternative) electron flow via cytochrome b559 (Cyt b559 ) within photosystem II (CEF-PSII)...
May 22, 2018: Photosynthesis Research
https://www.readbyqxmd.com/read/29789797/impact-of-static-magnetic-field-on-the-antioxidant-defence-system-of-mice-fibroblasts
#15
Marek Glinka, Stanisław Gawron, Aleksander Sieroń, Katarzyna Pawłowska-Góral, Grzegorz Cieślar, Karolina Sieroń
Results of research assessing the biological impact of static magnetic fields are controversial. So far, they have not provided a clear answer to their influence on cell functioning. Since the use of permanent magnets both in everyday life and in industry becomes more and more widespread, the investigations are continued in order to explain these controversies and to evaluate positive applications. The goal of current work was to assess the impact of static magnetic field of different intensities on redox homeostasis in cultures of fibroblasts...
2018: BioMed Research International
https://www.readbyqxmd.com/read/29789636/cypripedin-diminishes-an-epithelial-to-mesenchymal-transition-in-non-small-cell-lung-cancer-cells-through-suppression-of-akt-gsk-3%C3%AE-signalling
#16
Surassawadee Treesuwan, Boonchoo Sritularak, Pithi Chanvorachote, Varisa Pongrakhananon
Lung cancer appears to have the highest rate of mortality among cancers due to its metastasis capability. To achieve metastasis, cancer cells acquire the ability to undergo a switch from epithelial to mesenchymal behaviour, termed the epithelial-to-mesenchymal transition (EMT), which is associated with poor clinical outcomes. Drug discovery attempts have been made to find potent compounds that will suppress EMT. Cypripedin, a phenanthrenequinone isolated from Thai orchid, Dendrobium densiflorum, exhibits diverse pharmacological activities...
May 22, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29789524/hirsutine-induces-mptp-dependent-apoptosis-through-rock1-pten-pi3k-gsk3%C3%AE-pathway-in-human-lung-cancer-cells
#17
Rong Zhang, Guobing Li, Qian Zhang, Qin Tang, Jingbin Huang, Changpeng Hu, Yali Liu, Qing Wang, Wuyi Liu, Ning Gao, Shiwen Zhou
Hirsutine extracted from Uncaria rhynchophylla has been shown to exhibit anti-cancer activity. However, the molecular mechanism by which hirsutine exhibits anti-lung cancer activity remains unclear. In the present study, we showed that hirsutine induces apoptosis in human lung cancer cells via loss of mitochondrial membrane potential (∆ψm), adenosine triphosphate (ATP) depletion, ROS production, as well as cytochrome c release. Dephosphorylation of GSK3β is involved in hirsutine-mediated mitochondrial permeability transition pore (mPTP) opening through ANT1/CypD interaction...
May 22, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29789423/atp-binding-cassette-member-b5-abcb5-promotes-tumor-cell-invasiveness-in-human-colorectal-cancer
#18
Qin Guo, Tanja Grimmig, Gabriel Gonzalez, Anita Giobbie-Hurder, Gretchen Berg, Nolan Carr, Brian J Wilson, Pallavi Banerjee, Jie Ma, Jason S Gold, Bisweswar Nandi, Qin Huang, Ana Maria Waaga-Gasser, Christine G Lian, George F Murphy, Markus H Frank, Martin Gasser, Natasha Y Frank
ATP-binding cassette member B5 (ABCB5) mediates multidrug resistance (MDR) in diverse malignancies and confers clinically relevant 5-fluorouracil resistance to CD133-expressing cancer stem cells (CSCs) in human colorectal cancer (CRC). Because of its recently identified roles in normal stem cell maintenance, we hypothesized that ABCB5 might also serve MDR-independent functions in CRC. Here, in a prospective clinical study of 142 CRC patients, we found that ABCB5 mRNA transcripts previously reported not to be significantly expressed in healthy peripheral blood mononuclear cells are significantly enriched in patient peripheral blood specimens compared with non-CRC controls and correlate with CRC disease progression...
May 22, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29789376/optogenetic-activation-of-colon-epithelium-of-the-mouse-produces-high-frequency-bursting-in-extrinsic-colon-afferents-and-engages-visceromotor-responses
#19
Payal A Makadia, Sarah A Najjar, Jami L Saloman, Peter Adelman, Bin Feng, Joseph F Margiotta, Kathryn M Albers, Brian M Davis
Epithelial cells of the colon provide a vital interface between the internal environment (lumen of the colon) and colon parenchyma. To examine epithelial-neuronal signaling at this interface, we analyzed mice in which channelrhodopsin (ChR2) was targeted to either TRPV1-positive afferents or to villin expressing colon epithelial cells. Expression of a ChR2-EYFP fusion protein was directed to either primary sensory neurons or to colon epithelial cells by crossing Ai32 mice with TRPV1-Cre or villin-Cre mice, respectively...
May 22, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29789065/towards-a-synthetic-mitochondrion
#20
Olivier Biner, Thomas Schick, Aymar Abel Ganguin, Christoph von Ballmoos
Our group at the University of Bern uses biochemical and biophysical techniques to unravel details of the molecular mechanism of membrane proteins. Of special interest are the large multi-subunit complexes of the universally conserved respiratory chain and the ATP synthase that are found in mitochondria and aerobic bacteria. In a bottom-up approach using purified membrane proteins and synthetic lipids, we aim to mimic the basic processes of oxidative phosphorylation. We further develop methodologies to increase the complexity of such artificial systems, paving the way for a synthetic mitochondrion...
May 30, 2018: Chimia
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