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https://www.readbyqxmd.com/read/29676505/differential-reactivity-of-metal-binding-domains-of-copper-atpases-towards-cisplatin-and-colocalization-of-copper-and-platinum
#1
Tiantian Fang, Yao Tian, Siming Yuan, Yaping Sheng, Arnesano Fabio, Giovanni Natile, Yangzhong Liu
P-type ATPases, including MNK and WLN proteins, are responsible for active Cu efflux. These ATPases are also associated with resistance to cisplatin. In this work, we produced different metal-binding domains (MBDs) of ATPase (9 out of 12 domains), and compared their reactivity towards cisplatin. The reaction rates of the MBDs can be largely different; the reaction of MNK6 is about 6 times faster than that of WLN2. Copper coordination favors the platination of the MBDs to different extents. The rate of platination was generally grater for holo-MBDs than for apo-MBDS (particularly in the case of WLN4 and WLN2), however it was negligibly affected in the case of MNK6...
April 20, 2018: Chemistry: a European Journal
https://www.readbyqxmd.com/read/29675746/cabazitaxel-is-more-active-than-first-generation-taxanes-in-abcb1-cell-lines-due-to-its-reduced-affinity-for-p-glycoprotein
#2
George E Duran, Volker Derdau, Dietmar Weitz, Nicolas Philippe, Jörg Blankenstein, Jens Atzrodt, Dorothée Sémiond, Diego A Gianolio, Sandrine Macé, Branimir I Sikic
PURPOSE: The primary aim of this study was to determine cabazitaxel's affinity for the ABCB1/P-glycoprotein (P-gp) transporter compared to first-generation taxanes. METHODS: We determined the kinetics of drug accumulation and retention using [14 C]-labeled taxanes in multidrug-resistant (MDR) cells. In addition, membrane-enriched fractions isolated from doxorubicin-selected MES-SA/Dx5 cells were used to determine sodium orthovanadate-sensitive ATPase stimulation after exposure to taxanes...
April 19, 2018: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/29675630/saikosaponin-d-inhibits-proliferation-by-up-regulating-autophagy-via-the-camkk%C3%AE-ampk-mtor-pathway-in-adpkd-cells
#3
Weiwei Shi, Dechao Xu, Junhui Gu, Cheng Xue, Bo Yang, Lili Fu, Shuwei Song, Dongmei Liu, Wei Zhou, Jiayi Lv, Ke Sun, Meihan Chen, Changlin Mei
Autosomal dominant polycystic kidney disease (ADPKD) is a common heritable human disease. Recently, the role of repressed autophagy in ADPKD has drawn increasing attention. Here, we investigate the mechanism underlying the effect of Saikosaponin-d (SSd), a sarcoplasmic/endoplasmic reticulum Ca2+ ATPase pump (SERCA) inhibitor. We show that SSd suppresses proliferation in ADPKD cells by up-regulating autophagy. We found that treatment with SSd results in the accumulation of intracellular calcium, which in turn activates the CaMKKβ-AMPK signalling cascade, inhibits mTOR signalling and induces autophagy...
April 19, 2018: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/29675453/nafld-phenotype-in-patients-with-v-atpase-proton-pump-assembly-defects
#4
EDITORIAL
Jos C Jansen, David Wolthuis, Monique Van Scherpenzeel, Vlad Ratziu, Joost P H Drenth, Dirk J Lefeber
No abstract text is available yet for this article.
March 2018: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/29674140/impaired-ca-2-cycling-of-nonischemic-myocytes-contributes-to-sarcomere-dysfunction-early-after-myocardial-infarction
#5
Annette Kronenbitter, Florian Funk, Katarzyna Hackert, Simone Gorreßen, Dennis Glaser, Peter Boknik, Gereon Poschmann, Kai Stühler, Malgorzata Isić, Martina Krüger, Joachim P Schmitt
Changes in the nonischemic remote myocardium of the heart contribute to left ventricular dysfunction after ischemia and reperfusion (I/R). Understanding the underlying mechanisms early after I/R is crucial to improve the adaptation of the viable myocardium to increased mechanical demands. Here, we investigated the role of myocyte Ca2+ handling in the remote myocardium 24 h after 60 min LAD occlusion. Cardiomyocytes isolated from the basal noninfarct-related parts of wild type mouse hearts demonstrated depressed beat-to-beat Ca2+ handling...
April 16, 2018: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/29673976/effect-of-ultrasonic-field-on-the-enzyme-activities-and-ion-balance-of-potential-pathogen-saccharomyces-cerevisiae
#6
Junyan Liu, Lin Li, Lizhen Zhou, Bing Li, Zhenbo Xu
OBJECTIVES: This study aimed at investigating the enzyme activities and ion concentrations in potential pathogen S.cerevisiae upon ultrasonic treatment. METHODS: The activities of ATPase and antioxidase were identified by ATPase, SOD, and CAT assay kits following the instructions. Extracellular Ca2+ and K+ concentrations were determined in an atomic absorption spectrometer with calcium and potassium hollow-cathode lamps as radiation sources. RESULTS: SOD and CAT activities were enhanced by relatively low ultrasonic power at early time points and reduced to lower levels...
April 16, 2018: Microbial Pathogenesis
https://www.readbyqxmd.com/read/29671947/a-novel-inhibitor-of-the-new-antibiotic-resistance-are-protein-optra
#7
Xiaobo Zhong, Hua Xiang, Tiedong Wang, Ling Zhong, Di Ming, Linyan Nie, Fengjiao Cao, Bangbang Li, Junjie Cao, Dan Mu, Ke Ruan, Lin Wang, Dacheng Wang
The antibiotic resistance (ARE) subfamily of ABC (ATP-binding cassette) proteins confers resistance to a variety of clinically important ribosome-targeting antibiotics and plays an important role in infections caused by pathogenic bacteria. However, inhibitors of ARE proteins have rarely been reported. Here, OptrA, a new member of the ARE proteins, was used to study inhibitors of these types of proteins. We first confirmed that destroying the catalytic activity of OptrA could restore the sensitivity of host cells to antibiotics...
April 19, 2018: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/29670521/the-prenylflavonoid-xanthohumol-reduces-alzheimer-like-changes-and-modulates-multiple-pathogenic-molecular-pathways-in-the-neuro2a-app-swe-cell-model-of-ad
#8
Xianfeng Huang, Jing Wang, Xiao Chen, Pan Liu, Shujin Wang, Fangchen Song, Zaijun Zhang, Feiqi Zhu, Xinfeng Huang, Jianjun Liu, Guoqiang Song, Peter S Spencer, Xifei Yang
Alzheimer's disease (AD) is a progressive neurodegenerative disorder that has proved refractory to drug treatment. Given evidence of neuroprotection in animal models of ischemic stroke, we assessed the prenylflavonoid xanthohumol from the Common Hop ( Humulus lupulus L.) for therapeutic potential in murine neuroblastoma N2a cells stably expressing human Swedish mutant amyloid precursor protein (N2a/APP), a well-characterized cellular model of AD. The ELISA and Western-blot analysis revealed that xanthohumol (Xn) inhibited Aβ accumulation and APP processing, and that Xn ameliorated tau hyperphosphorylation via PP2A, GSK3β pathways in N2a/APP cells...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29670126/temporary-sequestration-of-cholesterol-and-phosphatidylcholine-within-extracellular-domains-of-abca1-during-nascent-hdl-generation
#9
Masato Ishigami, Fumihiko Ogasawara, Kohjiro Nagao, Hidehiko Hashimoto, Yasuhisa Kimura, Noriyuki Kioka, Kazumitsu Ueda
The quality and quantity of high-density lipoprotein (HDL) in blood plasma are important for preventing coronary artery disease. ATP-binding cassette protein A1 (ABCA1) and apolipoprotein A-I (apoA-I) play essential roles in nascent HDL formation, but controversy persists regarding the mechanism by which nascent HDL is generated. In the "direct loading model", apoA-I acquires lipids directly from ABCA1 while it is bound to the transporter. By contrast, in the "indirect model", apoA-I acquires lipids from the specific membrane domains created by ABCA1...
April 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29669961/aciduricity-and-acid-tolerance-mechanisms-of-streptococcus-anginosus
#10
Minoru Sasaki, Yoshitoyo Kodama, Yu Shimoyama, Taichi Ishikawa, Shigenobu Kimura
Although Streptococcus anginosus constitutes a proportion of the normal flora of the gastrointestinal and genital tracts, and the oral cavity, it has been reported that S. anginosus infection could be closely associated with abscesses at various body sites, infective endocarditis, and upper gastrointestinal cancers. The colonization in an acidic environment due to the aciduricity of S. anginosus could be the etiology of the systemic infection of the bacteria. To elucidate the aciduricity and acid tolerance mechanisms of the microbe, we examined the viability and growth of S...
April 17, 2018: Journal of General and Applied Microbiology
https://www.readbyqxmd.com/read/29669923/a-folding-nucleus-and-minimal-atp-binding-domain-of-hsp70-identified-by-single-molecule-force-spectroscopy
#11
Daniela Bauer, Sarah Meinhold, Roman P Jakob, Johannes Stigler, Ulrich Merkel, Timm Maier, Matthias Rief, Gabriel Žoldák
The folding pathways of large proteins are complex, with many of them requiring the aid of chaperones and others folding spontaneously. Along the folding pathways, partially folded intermediates are frequently populated; their role in the driving of the folding process is unclear. The structures of these intermediates are generally not amenable to high-resolution structural techniques because of their transient nature. Here we employed single-molecule force measurements to scrutinize the hierarchy of intermediate structures along the folding pathway of the nucleotide binding domain (NBD) of Escherichia coli Hsp70 DnaK...
April 18, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29669042/p-glycoprotein-on-blood-brain-barrier-plays-a-vital-role-in-fentanyl-brain-exposure-and-respiratory-toxicity-in-rats
#12
ChenChen Yu, Mei Yuan, HaiYing Yang, XiaoMei Zhuang, Hua Li
Fentanyl is a rapid-acting, short duration opioid analgesic agent. In recent years, increased prescription and illicit use of fentanyl drugs have led to major safety concerns and a growing death toll. However, the causes of fentanyl induced fatal adverse effects have not been thoroughly researched. The current study investigated P-glycoprotein (P-gp) modulated brain blood barrier (BBB) penetration of fentanyl and its resulting toxicity in vitro and in vivo. ATPase assays were performed together with bi-directional transport assays using Caco-2 cells in the presence and absence of tariquidar, a P-gp inhibitor, to confirm the P-gp substrate property of fentanyl...
April 14, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29668857/de-novo-mutations-of-the-atp6v1a-gene-cause-developmental-encephalopathy-with-epilepsy
#13
Anna Fassio, Alessandro Esposito, Mitsuhiro Kato, Hirotomo Saitsu, Davide Mei, Carla Marini, Valerio Conti, Mitsuko Nakashima, Nobuhiko Okamoto, Akgun Olmez Turker, Burcu Albuz, C Nur Semerci Gündüz, Keiko Yanagihara, Elisa Belmonte, Luca Maragliano, Keri Ramsey, Chris Balak, Ashley Siniard, Vinodh Narayanan, Chihiro Ohba, Masaaki Shiina, Kazuhiro Ogata, Naomichi Matsumoto, Fabio Benfenati, Renzo Guerrini
V-type proton (H+) ATPase (v-ATPase) is a multi-subunit proton pump that regulates pH homeostasis in all eukaryotic cells; in neurons, v-ATPase plays additional and unique roles in synapse function. Through whole exome sequencing, we identified de novo heterozygous mutations (p.Pro27Arg, p.Asp100Tyr, p.Asp349Asn, p.Asp371Gly) in ATP6V1A, encoding the A subunit of v-ATPase, in four patients with developmental encephalopathy with epilepsy. Early manifestations, observed in all patients, were developmental delay and febrile seizures, evolving to encephalopathy with profound delay, hypotonic/dyskinetic quadriparesis and intractable multiple seizure types in two patients (p...
April 13, 2018: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/29668377/pulsed-infrared-releases-ca-2-from-the-endoplasmic-reticulum-of-cultured-spiral-ganglion-neurons
#14
John N Barrett, Samantha Rincon, Jayanti Singh, Cristina Matthewman, Julio Pasos, Ellen F Barrett, Suhrud M Rajguru
We investigated the effects of pulsed infrared radiation (IR, 1863 nm) stimulation on cytosolic [Ca2+ ] in inner ear spiral ganglion neurons cultured from day 4 postnatal mice and loaded with a fluorescent Ca2+ indicator (fluo-4, -5F or -5N). IR pulse trains (200 µs, 200-250 Hz, 2-5 s) delivered via an optical fiber coupled to IR source produced a rapid, transient temperature increase of 6-11ºC (above a baseline of 24-30 ºC) and evoked transient increases in both nuclear and cytosolic [Ca2+ ] of 0.20 - 1...
April 18, 2018: Journal of Neurophysiology
https://www.readbyqxmd.com/read/29667915/chronic-lithium-treatment-induces-novel-patterns-of-pendrin-localization-and-expression
#15
Nathaniel J Himmel, Yirong Wang, Daniel A Rodriguez, Michael A Sun, Mitsi A Blount
Prolonged lithium treatment is associated with various renal side effects and is known to induce inner medullary collecting duct (IMCD) remodeling. In animals treated with lithium, the fraction of intercalated cells (ICs), which are responsible for acid-base homeostasis, increases as compared to renal principal cells (PCs). In order to investigate the intricacies of lithium-induced IMCD remodeling, male Sprague Dawley rats were fed a lithium-enriched diet for 0,1, 2, 3, 6, 9, or 12 weeks. Urine osmolality was decreased at 1 week, and from 2-12 weeks, animals were severely polyuric...
April 18, 2018: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29666337/mitochondrial-signatures-revealed-panmixia-in-lutjanus-argentimaculatus-forssk%C3%A3-l-1775
#16
A Gopalakrishnan, N Vineesh, Shihab Ismail, Muktha Menon, K V Akhilesh, N S Jeena, M P Paulton, P Vijayagopal
Mangrove red snapper, Lutjanus argentimaculatus is a commercially important fish. The genetic stock structure of L. argentimaculatus from Indian waters was identified using mitochondrial ATPase 6 and ATPase 8, and cytochrome b (Cytb) genes. A 842 bp region of ATPase 6/8 genes and 1105 bp region of Cytb gene were amplified in 120 samples from six different locations along the Indian coast and obtained 58 and 66 haplotypes, respectively. The high haplotype and low nucleotide diversity values along with mismatch distribution, Tajima's D and Fu's Fs analysis suggested a genetic bottleneck events or founder effect, with subsequent population expansion in L...
March 2018: Journal of Genetics
https://www.readbyqxmd.com/read/29666276/mine-conformational-switching-confers-robustness-on-self-organized-min-protein-patterns
#17
Jonas Denk, Simon Kretschmer, Jacob Halatek, Caroline Hartl, Petra Schwille, Erwin Frey
Protein patterning is vital for many fundamental cellular processes. This raises two intriguing questions: Can such intrinsically complex processes be reduced to certain core principles and, if so, what roles do the molecular details play in individual systems? A prototypical example for protein patterning is the bacterial Min system, in which self-organized pole-to-pole oscillations of MinCDE proteins guide the cell division machinery to midcell. These oscillations are based on cycling of the ATPase MinD and its activating protein MinE between the membrane and the cytoplasm...
April 16, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29666183/dilated-cardiomyopathy-myosin-mutants-have-reduced-force-generating-capacity
#18
Zoltan Ujfalusi, Carlos D Vera, Srbolujub M Mijailovich, Marina Svicevic, Elizabeth Choe Yu, Masataka Kawana, Kathleen Ruppel, James A Spudich, Michael A Geeves, Leslie A Leinwand
Dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM) can cause arrhythmias, heart failure, and cardiac death. Here, we functionally characterized the motor domains of five DCM-causing mutations in human β-cardiac myosin. Kinetic analyses of the individual events in the ATPase cycle revealed that each mutation alters different steps in this cycle. For example, different mutations gave enhanced or reduced rate constants of ATP binding, ATP hydrolysis, or ADP release or exhibited altered ATP, ADP, or actin affinity...
April 17, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29665121/homoharringtonine-could-induce-quick-protein-synthesis-of-psmd11-through-activating-mek1-erk1-2-signaling-pathway-in-pancreatic-cancer-cells
#19
Lele Wang, Linlin Zhao, Guo Wei, Dieter Saur, Barbara Seidler, Junyan Wang, Chuanxin Wang, Tonggang Qi
Pancreatic ductal adenocarcinoma (PDAC) remains one of the most devastating disease with the 5-year survival rate less than 6%. In this study, we investigated if inhibiting protein synthesis directly with homoharringtonine (HHT) could induce acute apoptosis in pancreatic cancer cells through quick depletion of multiple short-lived critical members of the central proteome, example, PSMD11(26S proteasome non-ATPase regulatory subunit 11). It was shown that although HHT could inhibit proliferation and growth of MiaPaCa-2 and PANC-1 cells in a time- and dose-dependent manner, only part of pancreatic cancer cells could be induced to die through acute apoptosis...
April 17, 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29664060/specialized-pro-resolving-mediators-regulate-alveolar-fluid-clearance-during-acute-respiratory-distress-syndrome
#20
REVIEW
Qian Wang, Song-Fan Yan, Yu Hao, Sheng-Wei Jin
Objective: Acute respiratory distress syndrome (ARDS) is an acute and lethal clinical syndrome that is characterized by the injury of alveolar epithelium, which impairs active fluid transport in the lung, and impedes the reabsorption of edema fluid from the alveolar space. This review aimed to discuss the role of pro-resolving mediators on the regulation of alveolar fluid clearance (AFC) in ARDS. Data Sources: Articles published up to September 2017 were selected from the PubMed, with the keywords of "alveolar fluid clearance" or "lung edema" or "acute lung injury" or "acute respiratory distress syndrome", and "specialized pro-resolving mediators" or "lipoxin" or "resolvin" or "protectin" or "maresin" or "alveolar epithelial cells" or "aspirin-triggered lipid mediators" or "carbon monoxide and heme oxygenase" or "annexin A1"...
April 20, 2018: Chinese Medical Journal
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