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https://www.readbyqxmd.com/read/28445983/transport-stress-induces-weight-loss-and-heart-injury-in-chicks-disruption-of-ionic-homeostasis-via-modulating-ion-transporting-atpases
#1
Zhao-Yang Li, Jia Lin, Feng Sun, Hui Li, Jun Xia, Xue-Nan Li, Jing Ge, Cong Zhang, Jin-Long Li
Transportation is inevitable in the poultry industry, and it can induce stress to chicks in varying degrees, such as mild discomfort, sometimes even death. However, the research about the effects of transport stress on the weight loss and heart injury of chicks is lacking. To elucidate the underlying mechanism of transport stress-induced effects, chicks were transported for 2h, 4h and 8h. The creatinine kinase (CK) activities, the ionic contents, the ATPases activities and the transcription of the ATPase associated subunits in chick heart were detected...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28444922/regulation-of-organelle-function-by-metformin
#2
REVIEW
Jeongho Kim, Young-Jai You
Metformin ameliorates hyperglycemia without the side effects of lactic acidosis or hypoglycemia. Metformin lowers the blood glucose level by decreasing hepatic glucose production in the liver and by increasing glucose uptake in the muscle. Recent studies show that metformin induces cell death in certain cancer cell lines by interfering with the metabolism of the cancer cells. Therefore, understanding the mechanisms of action for metformin will provide insights into how to better treat diabetes and other metabolic disorders and also into the development of new therapeutic drugs...
April 26, 2017: IUBMB Life
https://www.readbyqxmd.com/read/28444909/the-histone-methyltransferase-ezh2-is-a-therapeutic-target-in-small-cell-carcinoma-of-the-ovary-hypercalcemic-type
#3
Yemin Wang, Shary Yuting Chen, Anthony N Karnezis, Shane Colborne, Nancy Dos Santos, Jessica D Lang, William P D Hendricks, Krystal A Orlando, Damian Yap, Friedrich Kommoss, Marcel B Bally, Gregg B Morin, Jeffrey M Trent, Bernard E Weissman, David G Huntsman
Small cell carcinoma of the ovary, hypercalcemic type (SCCOHT) is a rare but aggressive and untreatable malignancy affecting young women. We and others recently discovered that SMARCA4, a gene encoding the ATPase of the SWI/SNF chromatin-remodeling complex, is the only gene recurrently mutated in the majority of SCCOHT. The low somatic complexity of SCCOHT genomes and the prominent role of the SWI/SNF chromatin-remodeling complex in transcriptional control of genes suggest that SCCOHT cells may rely on epigenetic rewiring for oncogenic transformation...
April 26, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28444399/development-of-a-multipurpose-scaffold-for-the-display-of-peptide-loops
#4
Maxim Rossmann, Sandra J Greive, Tommaso Moschetti, Michael Dinan, Marko Hyvönen
Protein-protein interactions (PPIs) determine a wide range of biological processes and analysis of these dynamic networks is increasingly becoming a mandatory tool for studying protein function. Using the globular ATPase domain of recombinase RadA as a scaffold, we have developed a peptide display system (RAD display), which allows for the presentation of target peptides, protein domains or full-length proteins and their rapid recombinant production in bacteria. The design of the RAD display system includes differently tagged versions of the scaffold, which allows for flexibility in the protein purification method, and chemical coupling for small molecule labeling or surface immobilization...
April 24, 2017: Protein Engineering, Design & Selection: PEDS
https://www.readbyqxmd.com/read/28443813/vacuolar-h-atpase-subunit-vma1p-functions-as-the-molecular-ligand-in-the-vacuole-targeting-fungicidal-activity-of-polymyxin-b
#5
Maki Iida, Keiichi Yamada, Yoshiya Nango, Yoshihiro Yamaguchi, Akira Ogita, Ken-Ichi Fujita, Toshio Tanaka
Polymyxin B (PMB) is a cationic cyclic peptide that can selectively inhibit the growth of Gram-negative bacteria by disrupting the outer membrane permeability barrier through binding to lipopolysaccharide (LPS). Here, a fluorescent PMB derivative (PMB-Ds) was applied to visually confirm the vacuole as a direct lethal target of PMB against fungal cells, which lack LPS. PMB-Ds could be visualized in the normal rounded vacuolar membrane of Saccharomyces cerevisiae cells, suggesting the presence of a molecular ligand assisting the vacuole-targeting mobilization of the peptide in the organism...
April 2017: Microbiology
https://www.readbyqxmd.com/read/28443245/overexpression-of-the-atpase-inhibitory-factor-1-favors-a-non-metastatic-phenotype-in-breast-cancer
#6
Lucía García-Ledo, Cristina Nuevo-Tapioles, Carmen Cuevas-Martín, Inmaculada Martínez-Reyes, Beatriz Soldevilla, Lucía González-Llorente, José M Cuezva
Partial suppression of mitochondrial oxidative phosphorylation and the concurrent activation of aerobic glycolysis is a hallmark of proliferating cancer cells. Overexpression of the ATPase inhibitory factor 1 (IF1), an in vivo inhibitor of the mitochondrial ATP synthase, is observed in most prevalent human carcinomas favoring metabolic rewiring to an enhanced glycolysis and cancer progression. Consistently, a high expression of IF1 in hepatocarcinomas and in carcinomas of the lung, bladder, and stomach and in gliomas is a biomarker of bad patient prognosis...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28443028/improved-model-of-proton-pump-crystal-structure-obtained-by-interactive-molecular-dynamics-flexible-fitting-expands-the-mechanistic-model-for-proton-translocation-in-p-type-atpases
#7
Dorota Focht, Tristan I Croll, Bjorn P Pedersen, Poul Nissen
The plasma membrane H(+)-ATPase is a proton pump of the P-type ATPase family and essential in plants and fungi. It extrudes protons to regulate pH and maintains a strong proton-motive force that energizes e.g., secondary uptake of nutrients. The only crystal structure of a H(+)-ATPase (AHA2 from Arabidopsis thaliana) was reported in 2007. Here, we present an improved atomic model of AHA2, obtained by a combination of model rebuilding through interactive molecular dynamics flexible fitting (iMDFF) and structural refinement based on the original data, but using up-to-date refinement methods...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28442261/identification-of-a-novel-fluoropyrrole-derivative-as-a-potassium-competitive-acid-blocker-with-long-duration-of-action
#8
Haruyuki Nishida, Yasuyoshi Arikawa, Keizo Hirase, Toshihiro Imaeda, Nobuhiro Inatomi, Yasunobu Hori, Jun Matsukawa, Yasushi Fujioka, Teruki Hamada, Motoo Iida, Mitsuyoshi Nishitani, Akio Imanishi, Hideo Fukui, Fumio Itoh, Masahiro Kajino
With the aim to find a novel long-lasting potassium-competitive acid blocker (P-CAB) that would perfectly overcome the limitations of proton pump inhibitors (PPIs), we tried various approaches based on pyrrole derivative 1b as a lead compound. As part of a comprehensive approach to identification of a new drug, we explored excellent compounds that have low lipophilicity by introducing a polar hetero-aromatic group at position 5 of the pyrrole ring. Among the compounds synthesized, fluoropyrrole derivative 37c, which has a 2-F-3-Py group at the fifth position, lower pKa, and much lower ClogP and logD values than 1b dose, showed potent gastric-acid suppressive action resulting from gastric H(+),K(+)-ATPase inhibition in animal models...
April 13, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28441865/unexpected%C3%A2-effects%C3%A2-of%C3%A2-k-%C3%A2-and%C3%A2-adenosine-triphosphate%C3%A2-on%C3%A2-the-thermal%C3%A2-stability%C3%A2-of%C3%A2-na-k-atpase
#9
M Agueda Placenti, Sergio Benjamín Benjamin Kaufman, F Luis Gonzalez Flecha, Rodolfo Martín González-Lebrero
Na(+),K(+)-ATPase is an integral membrane protein which couples ATP hydrolysis to the transport of three Na(+) out and two K(+) into the cell. The aim of this work is to characterize the effect of K(+), ATP and Mg(2+) (essential activator) on the Na(+),K(+)-ATPase thermal stability. In all conditions tested, thermal inactivation of the enzyme is concomitant with a structural change involving the ATP binding site and membrane-associated regions. Both ligands exert a clear stabilizing effect due to both enthalpic and entropic contributions...
April 25, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/28440616/discovery-and-characterization-of-a-eukaryotic-initiation-factor-4a-3-selective-inhibitor-that-suppresses-nonsense-mediated-mrna-decay
#10
Misa Iwatani-Yoshihara, Masahiro Ito, Yoshihiro Ishibashi, Hideyuki Oki, Toshio Tanaka, Daisuke Morishita, Takashi Ito, Hiromichi Kimura, Yasuhiro Imaeda, Samuel A Aparicio, Atsushi Nakanishi, Tomohiro Kawamoto
Eukaryotic initiation factor 4A-3 (eIF4A3) is an Asp-Glu-Ala-Asp (DEAD) box-family adenosine triphosphate (ATP)-dependent RNA helicase. Subtypes eIF4A1 and eIF4A2 are required for translation initiation, but eIF4A3 participates in the exon junction complex (EJC) and functions in RNA metabolism including nonsense-mediated RNA decay (NMD). No small molecules for NMD inhibition via selective inhibition of eIF4A3 have been discovered. Here we identified allosteric eIF4A3 inhibitors from a high-throughput screening campaign...
April 25, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28439563/mechanism-of-vps4-hexamer-function-revealed-by-cryo-em
#11
Min Su, Emily Z Guo, Xinqiang Ding, Yan Li, Jeffrey T Tarrasch, Charles L Brooks, Zhaohui Xu, Georgios Skiniotis
Vps4 is a member of AAA(+) ATPase (adenosine triphosphatase associated with diverse cellular activities) that operates as an oligomer to disassemble ESCRT-III (endosomal sorting complex required for transport III) filaments, thereby catalyzing the final step in multiple ESCRT-dependent membrane remodeling events. We used electron cryo-microscopy to visualize oligomers of a hydrolysis-deficient Vps4 (vacuolar protein sorting-associated protein 4) mutant in the presence of adenosine 5'-triphosphate (ATP). We show that Vps4 subunits assemble into an asymmetric hexameric ring following an approximate helical path that sequentially stacks substrate-binding loops along the central pore...
April 2017: Science Advances
https://www.readbyqxmd.com/read/28439275/arabidopsis-ala1-and-ala2-mediate-rnai-based-antiviral-immunity
#12
Biyun Zhu, Hua Gao, Gang Xu, Dewei Wu, Susheng Song, Hongshan Jiang, Shuifang Zhu, Tiancong Qi, Daoxin Xie
RNA intereferencing (RNAi) pathway regulates antiviral immunity and mediates plant growth and development. Despite considerable research efforts, a few components in RNAi pathway have been revealed, including ARGONAUTEs (AGOs), DICER-LIKEs (DCLs), RNA-dependent RNA polymerase 1 and 6 (RDR1/6), and ALTERED MERISTEM PROGRAM 1 (AMP1). In this study, we performed a forward genetic screening for enhancers of rdr6 via inoculation of CMV2aTΔ2b, a 2b-deficient Cucumber Mosaic Virus that is unable to suppress RNAi-mediated antiviral immunity...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28439258/diabetic-cardiomyopathy-an-immunometabolic-perspective
#13
REVIEW
Paras K Mishra, Wei Ying, Shyam Sundar Nandi, Gautam K Bandyopadhyay, Kaushik K Patel, Sushil K Mahata
The heart possesses a remarkable inherent capability to adapt itself to a wide array of genetic and extrinsic factors to maintain contractile function. Failure to sustain its compensatory responses results in cardiac dysfunction, leading to cardiomyopathy. Diabetic cardiomyopathy (DCM) is characterized by left ventricular hypertrophy and reduced diastolic function, with or without concurrent systolic dysfunction in the absence of hypertension and coronary artery disease. Changes in substrate metabolism, oxidative stress, endoplasmic reticulum stress, formation of extracellular matrix proteins, and advanced glycation end products constitute the early stage in DCM...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/28439008/interaction-of-proliferating-cell-nuclear-antigen-with-pms2-is-required-for-mutl%C3%AE-activation-and-function-in-mismatch-repair
#14
Jochen Genschel, Lyudmila Y Kadyrova, Ravi R Iyer, Basanta K Dahal, Farid A Kadyrov, Paul Modrich
Eukaryotic MutLα (mammalian MLH1-PMS2 heterodimer; MLH1-PMS1 in yeast) functions in early steps of mismatch repair as a latent endonuclease that requires a mismatch, MutSα/β, and DNA-loaded proliferating cell nuclear antigen (PCNA) for activation. We show here that human PCNA and MutLα interact specifically but weakly in solution to form a complex of approximately 1:1 stoichiometry that depends on PCNA interaction with the C-terminal endonuclease domain of the MutLα PMS2 subunit. Amino acid substitution mutations within a PMS2 C-terminal (721)QRLIAP motif attenuate or abolish human MutLα interaction with PCNA, as well as PCNA-dependent activation of MutLα endonuclease, PCNA- and DNA-dependent activation of MutLα ATPase, and MutLα function in in vitro mismatch repair...
April 24, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28438931/identification-of-antifungal-h-atpase-inhibitors-with-effect-on-the-plasma-membrane-potential
#15
Lasse Kjellerup, Sandra Gordon, Karen O'Hanlon Cohrt, William Dalby Brown, Anja Thoe Fuglsang, Anne-Marie Lund Winther
The plasma membrane H(+)-ATPase (Pma1) is an essential fungal protein and a proposed target for new antifungal medications. A small-molecule library containing ∼191,000 commercially available compounds was screened for inhibition of S. cerevisiae plasma membranes containing Pma1. The overall hit rate was 0.2 %, corresponding to 407 compounds.These hit compounds were further evaluated for ATPase selectivity and broad spectrum antifungal activity. Following this work, one Pma1 inhibitor series based on compound 14 and analogs, was selected for further evaluation...
April 24, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28438630/identification-of-anti-viral-activity-of-the-cardenolides-na-k-atpase-inhibitors-against-porcine-transmissible-gastroenteritis-virus
#16
Cheng-Wei Yang, Hsin-Yu Chang, Hsing-Yu Hsu, Yue-Zhi Lee, Hsun-Shuo Chang, Ih-Sheng Chen, Shiow-Ju Lee
A series of naturally occurring cardenolides that exhibit potent anti-transmissible gastroenteritis virus (TGEV) activity in swine testicular (ST) cells has been identified. In an immunofluorescence assay, these cardenolides were found to diminish the expressions of TGEV nucleocapsid and spike protein, which was used as an indication for viral replication; block TGEV infection induced apoptosis and cytopathic effects; and impart the same trend of inhibitory activity against Na(+)/K(+)-ATPase as for anti-TGEV activity...
April 21, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28438314/progression-of-experimental-autoimmune-encephalomyelitis-is-associated-with-up-regulation-of-major-sodium-transporters-in-the-mouse-kidney-cortex-under-a-normal-salt-diet
#17
Xiaoming Zhou, Balamurugan Packialakshmi, Yao Xiao, Saule Nurmukhambetova, Jason R Lees
Recent demonstrations of exacerbation of experimental autoimmune encephalomyelitis (EAE) by high salt diets prompted us to study whether EAE stimulated Na absorption by the renal cortex, a primary regulatory site for Na balance, even under a normal NaCl diet. We found that as EAE progressed from mild to severe symptoms, there were parallel increases in the protein abundance of NHE3 and αENaC and the Na,K-ATPase activity with an affiliated elevation of its β1-subunit protein. These effects are associated with increases in the protein levels of the well-known regulators SGK1 and scaffold NHERF2, and phosphorylation of ERK1/2...
April 18, 2017: Cellular Immunology
https://www.readbyqxmd.com/read/28436967/microtubule-minus-end-regulation-at-spindle-poles-by-an-aspm-katanin-complex
#18
Kai Jiang, Lenka Rezabkova, Shasha Hua, Qingyang Liu, Guido Capitani, A F Maarten Altelaar, Albert J R Heck, Richard A Kammerer, Michel O Steinmetz, Anna Akhmanova
ASPM (known as Asp in fly and ASPM-1 in worm) is a microcephaly-associated protein family that regulates spindle architecture, but the underlying mechanism is poorly understood. Here, we show that ASPM forms a complex with another protein linked to microcephaly, the microtubule-severing ATPase katanin. ASPM and katanin localize to spindle poles in a mutually dependent manner and regulate spindle flux. X-ray crystallography revealed that the heterodimer formed by the N- and C-terminal domains of the katanin subunits p60 and p80, respectively, binds conserved motifs in ASPM...
April 24, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28436536/early-vertebrate-origin-and-diversification-of-small-transmembrane-regulators-of-cellular-ion-transport
#19
Sergej Pirkmajer, Henriette Kirchner, Leonidas Lundell, Pavel V Zelenin, Juleen R Zierath, Kira S Makarova, Yuri I Wolf, Alexander V Chibalin
Small transmembrane proteins are important for regulation of cellular ion transport. The most prominent among these proteins are members of the FXYD family (FXYD1-12), which regulate Na(+) -K(+) -ATPase, and phospholamban, sarcolipin, myoregulin, and DWORF, which regulate the sarco-endoplasmic reticulum Ca(2+) -ATPase (SERCA). FXYDs and regulators of SERCA are present in fishes, as well as terrestrial vertebrates; however, their evolutionary origins and phylogenetic relationships are obscure, thus hampering comparative physiological studies...
April 24, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28435145/inhibition-of-na-k-atpase-by-5-6-7-8-tetrafluoro-3-hydroxy-2-phenylquinolin-4-1h-one
#20
Jaroslava Šeflová, Petra Čechová, Michal Biler, Pavel Hradil, Martin Kubala
Na(+)/K(+)-ATPase (NKA) is an enzyme of crucial importance for all animal cells. We examined the inhibitory effects of halogenated phenylquinolinones on NKA. The 5,6,7,8-tetrafluoro-3-hydroxy-2-phenylquinolin-4(1H)-one (TFHPQ) was identified as an efficient NKA inhibitor with IC50 near 10 μM. The inhibition by TFHPQ is particularly efficient at higher concentrations of K(+), where NKA adopts the E2 conformation. The experimental observations are in a good agreement with the outcomes from molecular docking...
April 20, 2017: Biochimie
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