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https://www.readbyqxmd.com/read/29055186/designed-inhibitors-with-hetero-linkers-for-gastric-proton-pump-h-k-atpase-steered-molecular-dynamics-and-metadynamics-studies
#1
Kalyanashis Jana, Tusar Bandyopadhyay, Bishwajit Ganguly
Acid suppressant SCH28080 and its derivatives reversibly reduce acid secretion activity of the H(+),K(+)-ATPase in a K(+) competitive manner. The results on homologation of the SCH28080 by varying the linker chain length suggested the improvement in efficacy. However, the pharmacokinetic studies reveal that the hydrophobic nature of the CH2 linker units may not help it to function as a better acid suppressant. We have exploited the role of linker unit to enhance the efficacy of such reversible acid suppressant drug molecules using hetero linker, i...
October 12, 2017: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/29054733/disrupted-ionic-homeostasis-in-ischemic-stroke-and-new-therapeutic-targets
#2
REVIEW
Hui-Jie Hu, Mingke Song
BACKGROUND: Stroke is a leading cause of long-term disability. All neuroprotectants targeting excitotoxicity have failed to become stroke medications. In order to explore and identify new therapeutic targets for stroke, we here reviewed present studies of ionic transporters and channels that are involved in ischemic brain damage. METHOD: We surveyed recent literature from animal experiments and clinical reports in the databases of PubMed and Elsevier ScienceDirect to analyze ionic mechanisms underlying ischemic cell damage and suggest promising ideas for stroke therapy...
October 17, 2017: Journal of Stroke and Cerebrovascular Diseases: the Official Journal of National Stroke Association
https://www.readbyqxmd.com/read/29054531/the-ammonia-transporter-rhcg-modulates-urinary-acidification-by-interacting-with-the-vacuolar-proton-atpases-in-renal-intercalated-cells
#3
Soline Bourgeois, Lisa Bounoure, Isabelle Mouro-Chanteloup, Yves Colin, Dennis Brown, Carsten A Wagner
Ammonium, stemming from renal ammoniagenesis, is a major urinary proton buffer and is excreted along the collecting duct. This process depends on the concomitant secretion of ammonia by the ammonia channel RhCG and of protons by the vacuolar-type proton-ATPase pump. Thus, urinary ammonium content and urinary acidification are tightly linked. However, mice lacking Rhcg excrete more alkaline urine despite lower urinary ammonium, suggesting an unexpected role of Rhcg in urinary acidification. RhCG and the B1 and B2 proton-ATPase subunits could be co-immunoprecipitated from kidney...
October 17, 2017: Kidney International
https://www.readbyqxmd.com/read/29054413/a-2-bp-deletion-in-the-mitochondrial-atp-6-gene-responsible-for-the-narp-neuropathy-ataxia-and-retinitis-pigmentosa-syndrome
#4
Patrick Mordel, Stéphane Schaeffer, Quentin Dupas, Marie-Alice Laville, Marion Gérard, Françoise Chapon, S Allouche
Mitochondrial (mt) DNA-associated NARP (neurogenic muscle weakness, ataxia, and retinitis pigmentosa) syndrome is due to mutation in the MT-ATP6 gene. We report the case of a 18-year-old man who presented with deafness, a myoclonic epilepsy, muscle weakness since the age of 10 and further developed a retinitis pigmentosa and ataxia. The whole mtDNA analysis by next-generation sequencing revealed the presence of the 2 bp microdeletion m.9127-9128 del AT in the ATP6 gene at 82% heteroplasmy in muscle and to a lower load in blood (10-20%) and fibroblasts (50%)...
October 17, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29054370/accessibility-of-axonal-g-protein-coupled-mu-opioid-receptors-requires-conceptual-changes-of-axonal-membrane-targeting-for-pain-modulation
#5
Shaaban A Mousa, Mohammed Shaqura, Mohammed Al-Madol, Sascha Tafelski, Baled I Khalefa, Mehdi Shakibaei, Michael Schäfer
The mechanisms of axonal trafficking and membrane targeting are well established for sodium channels, which are the principle targets for perineurally applied local anaesthetics. However, they have not been thoroughly investigated for G protein coupled receptors such as mu-opioid receptors (MOR). Focusing on these axonal mechanisms, we found that axonal MOR functionality is quite distinct in two different pain states, i.e. hindpaw inflammation and nerve injury. We observed axonal membrane MOR binding and functional G protein coupling exclusively at sites of CCI nerve injury...
October 17, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/29053956/assembly-of-the-whip-trim14-ppp6c-mitochondrial-complex-promotes-rig-i-mediated-antiviral-signaling
#6
Peng Tan, Lian He, Jun Cui, Chen Qian, Xin Cao, Meng Lin, Qingyuan Zhu, Yinyin Li, Changsheng Xing, Xiao Yu, Helen Y Wang, Rong-Fu Wang
Mitochondrial antiviral signaling platform protein (MAVS) acts as a central hub for RIG-I receptor proximal signal propagation. However, key components in the assembly of the MAVS mitochondrial platform that promote RIG-I mitochondrial localization and optimal activation are still largely undefined. Employing pooled RNAi and yeast two-hybrid screenings, we report that the mitochondrial adaptor protein tripartite motif (TRIM)14 provides a docking platform for the assembly of the mitochondrial signaling complex required for maximal activation of RIG-I-mediated signaling, consisting of WHIP and protein phosphatase PPP6C...
October 19, 2017: Molecular Cell
https://www.readbyqxmd.com/read/29053817/autophagic-flux-is-required-for-the-synthesis-of-triacylglycerols-and-ribosomal-protein-turnover-in-chlamydomonas
#7
Inmaculada Couso, María Esther Pérez-Pérez, Enrique Martínez-Force, Hee-Sik Kim, Yonghua He, James G Umen, José L Crespo, Peter Bozhkov
Autophagy is an intracellular catabolic process that allows cells to recycle unneeded or damaged material to maintain cellular homeostasis. This highly dynamic process is characterized by the formation of double-membrane vesicles called autophagosomes, which engulf and deliver the cargo to the vacuole. Flow of material through the autophagy pathway and its degradation in the vacuole is known as autophagic flux, and reflects the autophagic degradation activity. A number of assays have been developed to determine autophagic flux in yeasts, mammals, and plants, but it has not been examined yet in algae...
October 19, 2017: Journal of Experimental Botany
https://www.readbyqxmd.com/read/29053731/determination-of-%C3%AE-%C3%AE-and-%C3%AE%C2%BA-opioid-receptors-in-forebrain-cortex-of-rats-exposed-to-morphine-for-10-days-comparison-with-animals-after-20-days-of-morphine-withdrawal
#8
Hana Ujcikova, Martina Hlouskova, Kristina Cechova, Katerina Stolarova, Lenka Roubalova, Petr Svoboda
BACKGROUND: Chronic exposure of mammalian organism to morphine results in adaption to persistent high opioid tone through homeostatic adjustments. Our previous results indicated that in the frontal brain cortex (FBC) of rats exposed to morphine for 10 days, such a compensatory adjustment was detected as large up-regulation of adenylylcyclases I (8-fold) and II (2.5-fold). The other isoforms of AC (III-IX) were unchanged. Importantly, the increase of ACI and ACII was reversible as it disappeared after 20 days of morphine withdrawal...
2017: PloS One
https://www.readbyqxmd.com/read/29052811/four-saccharomyces-species-differ-in-their-tolerance-to-various-stresses-though-they-have-similar-basic-physiological-parameters
#9
Jana Zemančíková, Marie Kodedová, Klára Papoušková, Hana Sychrová
Saccharomyces species, which are mostly used in the food and beverage industries, are known to differ in their fermentation efficiency and tolerance of adverse fermentation conditions. However, the basis of their difference has not been fully elucidated, although their genomes have been sequenced and analyzed. Five strains of four Saccharomyces species (S. cerevisiae, S. kudriavzevii, S. bayanus, and S. paradoxus), when grown in parallel in laboratory conditions, exhibit very similar basic physiological parameters such as membrane potential, intracellular pH, and the degree to which they are able to quickly activate their Pma1 H(+)-ATPase upon glucose addition...
October 20, 2017: Folia Microbiologica
https://www.readbyqxmd.com/read/29052587/corrigendum-attenuation-of-na-k-atpase-mediated-oxidant-amplification-with-pnaktide-ameliorates-experimental-uremic-cardiomyopathy
#10
Jiang Liu, Jiang Tian, Muhammad Chaudhry, Kyle Maxwell, Yanling Yan, Xiaoliang Wang, Preeya T Shah, Asad A Khawaja, Rebecca Martin, Tylor J Robinette, Adee El-Hamdani, Michael W Dodrill, Komal Sodhi, Christopher A Drummond, Steven T Haller, David J Kennedy, Nader G Abraham, Zijian Xie, Joseph I Shapiro
This corrects the article DOI: 10.1038/srep34592.
October 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29052230/omecamtiv-mercabil-and-blebbistatin-modulate-cardiac-contractility-by-perturbing-the-regulatory-state-of-the-myosin-filament
#11
Thomas Kampourakis, Xuemeng Zhang, Yin-Biao Sun, Malcolm Irving
Contraction of heart muscle is triggered by a transient rise in intracellular free calcium concentration linked to a change in the structure of the actin-containing thin filaments that allows the head or motor domains of myosin from the thick filaments to bind to them and induce filament sliding. It is becoming increasingly clear that cardiac contractility is also regulated through structural changes in the thick filaments, although the molecular mechanisms underlying thick filament regulation are still relatively poorly understood...
October 20, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/29051551/reducing-sarcolipin-expression-mitigates-duchenne-muscular-dystrophy-and-associated-cardiomyopathy-in-mice
#12
Antanina Voit, Vishwendra Patel, Ronald Pachon, Vikas Shah, Mohammad Bakhutma, Erik Kohlbrenner, Joseph J McArdle, Louis J Dell'Italia, Jerry R Mendell, Lai-Hua Xie, Roger J Hajjar, Dongsheng Duan, Diego Fraidenraich, Gopal J Babu
Sarcolipin (SLN) is an inhibitor of the sarco/endoplasmic reticulum (SR) Ca(2+) ATPase (SERCA) and is abnormally elevated in the muscle of Duchenne muscular dystrophy (DMD) patients and animal models. Here we show that reducing SLN levels ameliorates dystrophic pathology in the severe dystrophin/utrophin double mutant (mdx:utr (-/-)) mouse model of DMD. Germline inactivation of one allele of the SLN gene normalizes SLN expression, restores SERCA function, mitigates skeletal muscle and cardiac pathology, improves muscle regeneration, and extends the lifespan...
October 20, 2017: Nature Communications
https://www.readbyqxmd.com/read/29051115/an-herbal-formula-consisting-of-schisandra-chinensis-turcz-baill-lycium-chinense-mill-and-eucommia-ulmoides-oliv-alleviates-disuse-muscle-atrophy-in-rats
#13
Seongguk Cho, Riwon Hong, Poorm Yim, Mijung Yeom, Bombi Lee, Woong Mo Yang, Jongki Hong, Hyang Sook Lee, Dae-Hyun Hahm
ETHNOPHARMACOLOGICAL RELEVANCE: Schisandra chinensis (Turcz.) Baill (SC), Lycium chinense Mill (LC) and Eucommia ulmoides Oliv (EU) are representative tonic herbal medicines that help to strengthen body muscles and bones making them stronger according to the Donguibogam, a tradition medical book of the Joseon Dynasty in Korea. AIM OF STUDY: To evaluate effects of an herbal formula consisting of SC, LC and EU on muscle atrophy in C2C12 myotubes and in a rat model of immobilization-induced muscle atrophy...
October 16, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/29050288/the-protective-effects-of-polysaccharide-of-atractylodes-macrocephala-koidz-pamk-on-the-chicken-spleen-under-heat-stress-via-antagonizing-apoptosis-and-restoring-the-immune-function
#14
Danning Xu, Bingxin Li, Nan Cao, Wanyan Li, Yunbo Tian, Yunmao Huang
Heat stress can cause immune organ dysfunction and apoptosis. Polysaccharide of Atractylodes macrocephala Koidz may have protective effects on immune organs. In this study, we established chicken models of Polysaccharide of Atractylodes macrocephala Koidz-heat stress interaction and detected the oxidative index, activities of mitochondrial complexes and ATPases as well as the ultrastructure in chicken spleens. Expression levels of cytokines, mitochondrial dynamics- and apoptosis-related genes were also measured...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29049367/the-inner-mantle-of-the-giant-clam-tridacna-squamosa-expresses-a-basolateral-na-k-atpase-%C3%AE-subunit-which-displays-light-dependent-gene-and-protein-expression-along-the-shell-facing-epithelium
#15
Mel V Boo, Kum C Hiong, Celine Y L Choo, Anh H Cao-Pham, Wai P Wong, Shit F Chew, Yuen K Ip
Na+/K+-ATPase (NKA) is essential for maintaining the Na+ and K+ gradients, and supporting the secondary active transport of certain ions/molecules, across the plasma membrane of animal cells. This study aimed to clone the NKA α-subunit (NKAα) from the inner mantle adjacent to the extrapallial fluid of Tridacna squamosa, to determine its subcellular localization, and to examine the effects of light exposure on its transcript level and protein abundance. The cDNA coding sequence of NKAα from T. squamosa comprised 3105 bp, encoding 1034 amino acids with an estimated molecular mass of 114 kDa...
2017: PloS One
https://www.readbyqxmd.com/read/29047027/a-possible-mechanism-for-low-affinity-of-silkworm-na-k-atpase-for-k
#16
Haruo Homareda, Masahiro Otsu, Sachiko Yamamoto, Makoto Ushimaru, Sayaka Ito, Toshiyuki Fukutomi, Taeho Jo, Yoshinobu Eishi, Yukichi Hara
The affinity for K(+) of silkworm nerve Na(+)/K(+)-ATPase is markedly lower than that of mammalian Na(+)/K(+)-ATPase (Homareda 2010). In order to obtain clues on the molecular basis of the difference in K(+) affinities, we cloned cDNAs of silkworm (Bombyx mori) nerve Na(+)/K(+)-ATPase α and β subunits, and analyzed the deduced amino acid sequences. The molecular masses of the α and β subunits were presumed to be 111.5 kDa with ten transmembrane segments and 37.7 kDa with a single transmembrane segment, respectively...
October 19, 2017: Journal of Bioenergetics and Biomembranes
https://www.readbyqxmd.com/read/29046690/ala6-a-p4-type-atpase-is-involved-in-heat-stress-responses-in-arabidopsis-thaliana
#17
Yue Niu, Dong Qian, Baiyun Liu, Jianchao Ma, Dongshi Wan, Xinyu Wang, Wenliang He, Yun Xiang
Maintaining lipid membrane integrity is an essential aspect of plant tolerance to high temperature. P4-type ATPases are responsible for flipping and stabilizing asymmetric phospholipids in membrane systems, though their functions in stress tolerance are not entirely clear. Aminophospholipid ATPase6 (ALA6) is a member of the P4-type ATPase family, which has 12 members in Arabidopsis thaliana. Here, we show that a loss-of-function mutant of ALA6 (ala6) exhibits clear sensitivity to heat stress, including both basal and acquired thermotolerance treatments...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/29046367/pkc%C3%AE-silencing-alleviates-saturated-fatty-acid-induced-er-stress%C3%A2-by-enhancing-serca-activity
#18
Shujie Lai, Yan Li, Yi Kuang, Hongli Cui, Yang Yang, Wenjing Sun, Kaijun Liu, Dongfeng Chen, Qixian Yan, Liangzhi Wen
Aim : Protein Kinase C δ (PKCδ) plays an important role in non-alcoholic fatty liver disease (NAFLD), however the mechanism remains unknown. This study explored the role of PKCδ in NAFLD development and investigated the relationships between PKCδ, calcium homeostasis and endoplasmic reticulum stress (ERS). Methods : Hepatic steatosis cell model was induced by palmitic acid (PA) in L02 cells. Lipid accretion was evaluated using Oil Red O staining and a triglyceride detection kit. PKCδ was down-regulated by siRNA...
October 18, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/29046297/renal-and-colonic-potassium-transporters-in-the-pregnant-rat
#19
Crystal A West, Paul A Welling, David A West, Richard A Coleman, Kit-Yan Cheng, Chao Chen, Thomas D DuBose, Jill W Verlander, Chris Baylis, Michelle L Gumz
Gestational potassium retention, most of which occurs during late pregnancy, is essential for fetal development. The purpose of this study was to examine mechanisms underlying changes in potassium handling by the kidney and colon in pregnancy. We found that potassium intake and renal excretion increased in late pregnancy while fecal potassium excretion remained unchanged and that pregnant rats exhibited net potassium retention. By qPCR we found markedly increased H+/K+-ATPase type2 (HKA2) mRNA expression in cortex and OM of late pregnant vs virgin...
October 18, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29045865/cooperative-nucleotide-binding-in-hsp90-and-its-regulation-by-aha1
#20
Philipp Wortmann, Markus Götz, Thorsten Hugel
The function of the molecular chaperone Hsp90 depends on large conformational changes, the rearrangement of local motifs, and the binding and hydrolysis of ATP. The size and complexity of the Hsp90 system impedes the detailed investigation of their interplay using standard methods. To overcome this limitation, we developed a three-color single-molecule FRET assay to study the interaction of Hsp90 with a fluorescently labeled reporter nucleotide in detail. It allows us to directly observe the cooperativity between the two nucleotide binding pockets in the protein dimer...
October 17, 2017: Biophysical Journal
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