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https://www.readbyqxmd.com/read/28324828/evaluation-of-dna-damage-and-physiological-responses-in-nile-tilapia-oreochromis-niloticus-linnaeus-1758-exposed-to-sub-lethal-diclofenac-dcf
#1
Pramod K Pandey, Malachy N O Ajima, Kundan Kumar, Nalini Poojary, Saurav Kumar
The frequent bioaccumulation of pharmaceuticals in the aquatic ecosystem has raised a concern about their possible ecotoxicological consequences. DNA damage, haematological changes and activities of oxidative stress enzymes in Nile tilapia, Oreochromis niloticus in response to diclofenac (DCF) exposure were investigated for up to 60 days at the concentrations of 0.17, 0.34 and 0.68mgL(-1) in the fish liver. Evaluation of genotoxic effects of the drug in the liver, using single-cell gel electrophoresis, showed DNA damage on exposure at the concentrations of 0...
March 8, 2017: Aquatic Toxicology
https://www.readbyqxmd.com/read/28324674/osteoblast-osteoclast-interactions
#2
Xiao Chen, Zhongqiu Wang, Na Duan, Guoying Zhu, Edward M Schwarz, Chao Xie
Bone homeostasis depends on the resorption of bones by osteoclasts and formation of bones by the osteoblasts. Imbalance of this tightly coupled process can cause diseases such as osteoporosis. Thus, the mechanisms that regulate communication between osteoclasts and osteoblasts are critical to bone cell biology. It has been shown that osteoblasts and osteoclasts can communicate with each other through direct cell-cell contact, cytokines, and extracellular matrix interaction. Osteoblasts can affect osteoclast formation, differentiation, or apoptosis through several pathways, such as OPG/RANKL/RANK, RANKL/LGR4/RANK, Ephrin2/ephB4, and Fas/FasL pathways...
February 8, 2017: Connective Tissue Research
https://www.readbyqxmd.com/read/28320096/a-natural-compound-jaceosidin-ameliorates-endoplasmic-reticulum-stress-and-insulin-resistance-via-upregulation-of-serca2b
#3
Zijun Ouyang, Wanshuai Li, Qianqian Meng, Qi Zhang, Xingqi Wang, Ahmed Elgehama, Xudong Wu, Yan Shen, Yang Sun, Xuefeng Wu, Qiang Xu
Increased endoplasmic reticulum (ER) stress has emerged as a vital contributor to dysregulated glucose homeostasis, and impaired function of sarco-endoplasmic reticulum Ca(2+)-ATPase 2b (SERCA2b) is one of the central mechanisms underlying ER stress. In this study, we reported that SERCA2b upregulation contributed to the amelioration of ER stress and insulin resistance by a small natural compound jaceosidin. In a model of differentiated C2C12 myotubes, jaceosidin-triggered SERCA2b upregulation enhanced insulin sensitivity and decreased ER stress...
March 17, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28319892/mitochondrial-hyperpolarization-in-ipsc-derived-neurons-from-patients-of-ftdp-17-with-10-16-mapt-mutation-leads-to-oxidative-stress-and-neurodegeneration
#4
Noemí Esteras, Jonathan D Rohrer, John Hardy, Selina Wray, Andrey Y Abramov
Tau protein inclusions are a frequent hallmark of a variety of neurodegenerative disorders. The 10+16 intronic mutation in MAPT gene, encoding tau, causes frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17), by altering the splicing of the gene and inducing an increase in the production of 4R tau isoforms, which are more prone to aggregation. However, the molecular mechanisms linking increased 4R tau to neurodegeneration are not well understood. Here, we have used iPSC-derived neurons from patients of FTDP-17 carrying the 10+16 mutation to study the molecular mechanisms underlying neurodegeneration...
March 10, 2017: Redox Biology
https://www.readbyqxmd.com/read/28319644/the-retinal-relaxing-factor-update-on-an-enigmatic-regulator-of-the-retinal-circulation
#5
Laura Vanden Daele, Charlotte Boydens, Bart Pauwels, Johan Van de Voorde
The retinal circulation is regulated by different local factors and might include the retinal relaxing factor (RRF). This factor is found to be continuously released by the retina and relaxes smooth muscle cells. This review describes the current knowledge about the RRF. Despite many research efforts, the cellular source, identity, mechanism, and physiological role of the RRF remain largely unknown. Thus far, it seems that the RRF is a hydrophilic, thermostable, diffusible chemical messenger, which characteristics do not correspond with most well-known endogenous vasorelaxants...
March 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28319179/biophysical-comparison-of-atp-driven-proton-pumping-mechanisms-suggests-a-kinetic-advantage-for-the-rotary-process-depending-on-coupling-ratio
#6
Ramu Anandakrishnan, Daniel M Zuckerman
ATP-driven proton pumps, which are critical to the operation of a cell, maintain cytosolic and organellar pH levels within a narrow functional range. These pumps employ two very different mechanisms: an elaborate rotary mechanism used by V-ATPase H+ pumps, and a simpler alternating access mechanism used by P-ATPase H+ pumps. Why are two different mechanisms used to perform the same function? Systematic analysis, without parameter fitting, of kinetic models of the rotary, alternating access and other possible mechanisms suggest that, when the ratio of protons transported per ATP hydrolyzed exceeds one, the one-at-a-time proton transport by the rotary mechanism is faster than other possible mechanisms across a wide range of driving conditions...
2017: PloS One
https://www.readbyqxmd.com/read/28318378/pexophagy-is-responsible-for-65-of-cases-of-peroxisome-biogenesis-disorders
#7
Taras Y Nazarko
Peroxisome biogenesis disorders (PBDs) is a group of diseases caused by mutations in one of the peroxins, proteins responsible for biogenesis of the peroxisomes. In recent years, it became clear that many peroxins (e.g., PEX3 and PEX14) play additional roles in peroxisome homeostasis (such as promoting autophagic degradation of peroxisomes or pexophagy), which are often opposite to their originally established functions in peroxisome formation and maintenance. Even more interesting, the peroxins that make up the peroxisomal AAA ATPase complex (AAA-complex) in yeast (Pex1, Pex6 and Pex15) or mammals (PEX1, PEX6, PEX26) are responsible for the downregulation of pexophagy...
February 28, 2017: Autophagy
https://www.readbyqxmd.com/read/28317920/kus121-a-vcp-modulator-attenuates-ischemic-retinal-cell-death-via-suppressing-endoplasmic-reticulum-stress
#8
Masayuki Hata, Hanako O Ikeda, Chinami Kikkawa, Sachiko Iwai, Yuki Muraoka, Tomoko Hasegawa, Akira Kakizuka, Nagahisa Yoshimura
Ischemic neural damages cause several devastating diseases, including brain stroke and ischemic retinopathies, and endoplasmic reticulum (ER) stress has been proposed to be the underlying mechanism of the neuronal cell death of these conditions. We previously synthesized Kyoto University substances (KUSs) as modulators of valosin-containing protein (VCP); KUSs inhibit VCP ATPase activity and protect cells from different cell death-inducing insults. Here, we examined the efficacy of KUS121 in a rat model of retinal ischemic injury...
March 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28317806/mycobacterium-lepraemurium-uses-tlr-6-and-mr-but-not-lipid-rafts-or-dc-sign-to-gain-access-into-mouse-macrophages
#9
Mayra Silva-Miranda, Patricia Arce-Paredes, Oscar Rojas-Espinosa
OBJECTIVE/BACKGROUND: Mycobacterium lepraemurium (MLM), the etiologic agent of murine leprosy, is an intracellular parasite of macrophages; the mechanism used by this bacterium to enter macrophages is not known. The fate of the MLM phagosome inside macrophages is also unknown. This study was conducted to investigate how MLM enters macrophages and to define the maturation process of MLM phagosome inside macrophages. MATERIALS AND METHODS: Peritoneal macrophages were incubated in the presence of mannan-bovine serum albumin (BSA), and antibodies to known macrophage receptors, including, anti-FcγRIII/RII (anti-CD16/32), anti-CD35 (anti-CR1), anti-TLR2, anti-TLR4, anti-TLR6, anti-CD14, and anti-dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN)...
January 2017: International Journal of Mycobacteriology
https://www.readbyqxmd.com/read/28317223/cancer-with-low-cathepsin-d-levels-is-susceptible-to-v-atpase-inhibition
#10
Satoshi Kitazawa, Satoru Nishizawa, Hideyuki Nakagawa, Masaaki Funata, Kazuho Nishimura, Tomoyoshi Soga, Takahito Hara
Vacuolar (H(+) )-ATPases (V-ATPases) have important roles in the supply of nutrients to tumors by mediating autophagy and the endocytic uptake of extracellular fluids. Accordingly, V-ATPases are attractive therapeutic targets for cancer. However, the clinical use of V-ATPase inhibitors as anti-cancer drugs has not been realized, possibly owing to their high toxicity in humans. V-ATPase inhibition may be an appropriate strategy in highly susceptible cancers. In this study, we explored markers of V-ATPase inhibitor sensitivity...
March 19, 2017: Cancer Science
https://www.readbyqxmd.com/read/28316890/computer-modelling-reveals-new-conformers-of-the-atp-binding-loop-of-na-k-atpase-involved-in-the-transphosphorylation-process-of-the-sodium-pump
#11
Gracian Tejral, Bruno Sopko, Alois Necas, Wilhelm Schoner, Evzen Amler
Hydrolysis of ATP by Na(+)/K(+)-ATPase, a P-Type ATPase, catalyzing active Na(+) and K(+) transport through cellular membranes leads transiently to a phosphorylation of its catalytical α-subunit. Surprisingly, three-dimensional molecular structure analysis of P-type ATPases reveals that binding of ATP to the N-domain connected by a hinge to the P-domain is much too far away from the Asp(369) to allow the transfer of ATP's terminal phosphate to its aspartyl-phosphorylation site. In order to get information for how the transfer of the γ-phosphate group of ATP to the Asp(369) is achieved, analogous molecular modeling of the M4-M5 loop of ATPase was performed using the crystal data of Na(+)/K(+)-ATPase of different species...
2017: PeerJ
https://www.readbyqxmd.com/read/28316131/evaluation-of-potential-rna-interference-target-genes-to-control-cotton-mealybug-phenacoccus-solenopsis-hemiptera-pseudococcuidae
#12
Arif M Khan, Muhammad Ashfaq, Azhar A Khan, Muhammad T Naseem, Shahid Mansoor
RNA interference (RNAi) of vital insect genes is a potential tool for targeted pest control. However, selection of the right target genes is a challenge because the RNAi efficacy is known to vary among insect species. Cotton mealybug, Phenacoccus solenopsis, is a phloem-feeding economically important crop pest. We evaluated the RNAi of two vital genes, Bursicon (PsBur) and V-ATPase (PsV-ATPase) as potential targets in P. solenopsis for its control. PCR fragments of PsBur and PsV-ATPase were amplified using cDNA synthesized from the total RNA...
March 18, 2017: Insect Science
https://www.readbyqxmd.com/read/28315791/neurotoxic-effects-molecular-responses-and-oxidative-stress-biomarkers-in-nile-tilapia-oreochromis-niloticus-linnaeus-1758-exposed-to-verapamil
#13
Malachy N O Ajima, Pramod K Pandey, Kundan Kumar, Nalini Poojary
Pharmaceutical drugs and their metabolites are detected in aquatic ecosystems and have been reported to cause ecotoxicological consequences to resident aquatic organisms The study investigated the effects of acute and long-term exposure to verapamil on activities of acetylcholinesterase and antioxidant enzymes as well as mRNA expression of stress-related genes in brain and muscle tissues of Nile tilapia, Oreochromis niloticus. The 96h LC50 of verapamil to O. niloticus was 2.29mg L(-1). Exposure to sub-lethal concentrations of verapamil (0...
March 15, 2017: Comparative Biochemistry and Physiology. Toxicology & Pharmacology: CBP
https://www.readbyqxmd.com/read/28306370/genetic-diversity-of-atp8-and-atp6-genes-is-associated-with-high-altitude-adaptation-in-yak
#14
Jie Wang, Yu Shi, Mauricio A Elzo, Shuzhang Dang, Xianbo Jia, Songjia Lai
ATP synthase 8 (ATP8) and ATPase synthase 6 (ATP6) play an important role in mitochondrial ATPase assembly. Mutations in either of these units could affect the ATP processing and the respiration chain in mitochondria. To find out if there were differences in gene diversity between Tibetan yaks and domestic cattle, we sequenced the ATP8 and ATP6 genes in 66 Tibetan yaks and 81 domestic cattle. We identified 20 SNPs in the ATP8 gene and 60 SNPs in the ATP6 gene. Ten SNPs detected in ATP8 were probably positively associated with high-altitude adaptation, of which SNPs m...
March 17, 2017: Mitochondrial DNA. Part A. DNA Mapping, Sequencing, and Analysis
https://www.readbyqxmd.com/read/28303975/a-conserved-inter-domain-communication-mechanism-regulates-the-atpase-activity-of-the-aaa-protein-drg1
#15
Michael Prattes, Mathias Loibl, Gertrude Zisser, Daniel Luschnig, Lisa Kappel, Ingrid Rössler, Manuela Grassegger, Altijana Hromic, Elmar Krieger, Karl Gruber, Brigitte Pertschy, Helmut Bergler
AAA-ATPases fulfil essential roles in different cellular pathways and often act in form of hexameric complexes. Interaction with pathway-specific substrate and adaptor proteins recruits them to their targets and modulates their catalytic activity. This substrate dependent regulation of ATP hydrolysis in the AAA-domains is mediated by a non-catalytic N-terminal domain. The exact mechanisms that transmit the signal from the N-domain and coordinate the individual AAA-domains in the hexameric complex are still the topic of intensive research...
March 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28303574/functional-impact-of-an-oculopharyngeal-muscular-dystrophy-mutation-in-pabpn1
#16
Maricela García-Castañeda, Ana Victoria Vega, Rocío Rodríguez, Maria Guadalupe Montiel-Jaen, Bulmaro Cisneros, Angel Zarain-Herzberg, Guillermo Avila
Oculopharyngeal muscular dystrophy (OPMD) is linked to mutations in the gene encoding poly(A)-binding protein nuclear 1 (PABPN1). OPMD mutations consist in an expansion of a tract that contains 10 alanines (to 12-17). The disease courses with muscle weakness that begins in adulthood, but the underlying mechanism is unclear. Here we investigated functional effects of PABPN1 and an OPMD mutation (PABPN1-17A), using myotubes transfected with cDNAs encoding these proteins (GFP-tagged). PABPN1 stimulated myoblast fusion (100%), but PABPN1-17A failed to mimic this effect...
March 16, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28303028/alectinib-ch5424802-antagonizes-abcb1-and-abcg2-mediated-multidrug-resistance-in-vitro-in-vivo-and-ex-vivo
#17
Ke Yang, Yifan Chen, Kenneth Kin Wah To, Fang Wang, Delan Li, Likun Chen, Liwu Fu
Alectinib, an inhibitor of anaplastic lymphoma kinase (ALK), was approved by the Food and Drug Administration (FDA) for the treatment of patients with ALK-positive non-small cell lung cancer (NSCLC). Here we investigated the reversal effect of alectinib on multidrug resistance (MDR) induced by ATP-binding cassette (ABC) transporters, which is the primary cause of chemotherapy failure. We provide the first evidence that alectinib increases the sensitivity of ABCB1- and ABCG2-overexpressing cells to chemotherapeutic agents in vitro and in vivo...
March 17, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28302728/a-high-and-phosphatidylinositol-4-phosphate-pi4p-dependent-atpase-activity-for-the-drs2p-cdc50p-flippase-after-removal-of-its-n-and-c-terminal-extensions
#18
Hassina Azouaoui, Cédric Montigny, Thibaud Dieudonné, Philippe Champeil, Aurore Jacquot, José Luis Vázquez-Ibar, Pierre Le Maréchal, Jakob Ulstrup, Miriam-Rose Ash, Joseph A Lyons, Poul Nissen, Guillaume Lenoir
P4-ATPases, also known as phospholipid flippases, are responsible for creating and maintaining transbilayer lipid asymmetry in eukaryotic cell membranes. Here, we use limited proteolysis to investigate the role of the N- and C-termini in ATP hydrolysis and auto-inhibition of the yeast flippase Drs2p/Cdc50p. We show that limited proteolysis of the detergent-solubilized and purified yeast flippase may result in more than one order of magnitude increase of its ATPase activity, which remains dependent on phosphatidylinositol-4-phosphate (PI4P), a regulator of this lipid flippase, and specific to a phosphatidylserine substrate...
March 16, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28302665/calpain-mobilizes-atg9-bif-1-vesicles-from-golgi-stacks-upon-autophagy-induction-by-thapsigargin
#19
Elena Marcassa, Marzia Raimondi, Tahira Anwar, Eeva-Liisa Eskelinen, Michael P Myers, Gianluca Triolo, Claudio Schneider, Francesca Demarchi
CAPNS1 is essential for stability and function of the ubiquitous calcium dependent proteases micro- and milli-calpain. Upon the inhibition of the endoplasmic reticulum Ca2+ ATPase by 100nM thapsigargin, both micro-calpain and autophagy are activated in human U2OS osteosarcoma cells in a CAPNS1 dependent manner. As reported for other autophagy triggers, thapsigargin treatment induces Golgi fragmentation and fusion of Atg9/Bif-1 containing vesicles with LC3 bodies in control cells. On the opposite, CAPNS1 depletion is coupled to an accumulation of LC3 bodies and Rab5 early endosomes...
March 16, 2017: Biology Open
https://www.readbyqxmd.com/read/28302654/palmitate-induced-vacuolar-type-h-atpase-inhibition-feeds-forward-into-insulin-resistance-and-contractile-dysfunction
#20
Yilin Liu, Laura K M Steinbusch, Miranda Nabben, Dimitris Kapsokalyvas, Marc van Zandvoort, Patrick Schönleitner, Gudrun Antoons, Peter J Simons, Will A Coumans, Amber Geomini, Dipanjan Chanda, Jan F C Glatz, Dietbert Neumann, Joost J F P Luiken
Dietary fat overconsumption leads to myocardial lipid accumulation through mechanisms that are incompletely resolved. Previously, we identified increased translocation of the fatty acid transporter CD36 from its endosomal storage compartment to the sarcolemma as primary mechanism of excessive myocellular lipid import. Here, we show that increased CD36 translocation is caused by alkalinization of endosomes due to inhibition of proton pumping activity of vacuolar-type H(+)-ATPase (v-ATPase). Endosomal alkalinization was observed in hearts from rats fed a lard-based high fat-diet and in rodent and human cardiomyocytes upon palmitate overexposure, and appeared as early lipid-induced event preceding the onset of insulin resistance...
March 16, 2017: Diabetes
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