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https://www.readbyqxmd.com/read/29667627/propofol-inhibits-hela-cells-by-impairing-autophagic-flux-via-amp-activated-protein-kinase-ampk-activation-and-endoplasmic-reticulum-stress-regulated-by-calcium
#1
Xi Chen, Kai Li, Guoqing Zhao
BACKGROUND Propofol has antitumor effects against various cancers. However, the mechanism of action of propofol in HeLa human cervical cancer cells has not been elucidated. MATERIAL AND METHODS We treated HeLa human cervical cancer cells with different concentrations of propofol. Cell viability was evaluated with Cell Counting Kit-8 and apoptosis was analyzed by annexin V-fluorescein isothiocyanate and propidium iodide staining and flow cytometry. Autophagosome formation was evaluated based on microtubule-associated protein light chain (LC)3 conversion and light chain 3 puncta formation...
April 18, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/29666376/author-correction-identification-and-characterization-of-sse15206-a-microtubule-depolymerizing-agent-that-overcomes-multidrug-resistance
#2
Safia Manzoor, Aishah Bilal, Sardraz Khan, Rahim Ullah, Sunniya Iftikhar, Abdul-Hamid Emwas, Meshari Alazmi, Xin Gao, Ali Jawaid, Rahman Shah Zaib Saleem, Amir Faisal
A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.
April 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29665476/bioactive-norditerpenoids-from-cephalotaxus-fortunei-var-alpina-and-c-lanceolata
#3
Ling Ni, Xiu-Hong Zhong, Xiao-Jiao Chen, Bing-Jie Zhang, Mei-Fen Bao, Xiang-Hai Cai
Twenty-eight naturally occurring Cephalotaxus tropone analogues, including 19 previously undescribed ones, were identified from Cephalotaxus fortunei Hook. var. alpina H. L. Li and C. lanceolata K. M. Feng. The presence of the C20 cephinoids A-E revealed that these tropones were assigned to the norditerpenoids and were perhaps derived from labdane-type diterpenoids. These norditerpenoids showed excellent cytotoxicity against human cancer cells (IC50 , 20-0.1 μM) in vitro. The SAR (structure-activity relationship) analysis disclosed that the tropone moiety and the lactone ring were crucial structural features for the observed activities...
April 14, 2018: Phytochemistry
https://www.readbyqxmd.com/read/29663696/interactions-of-%C3%AE-tubulin-isotypes-with-glutathione-in-differentiated-neuroblastoma-cells-subject-to-oxidative-stress
#4
Jiayan Guo, Hong Seok Kim, Reto Asmis, Richard F Ludueña
Microtubules are a major component of the neuronal cytoskeleton. Tubulin, the subunit protein of microtubules, is an α/β heterodimer. Both α and β exist as families of isotypes, whose members are encoded by different genes and have different amino acid sequences. The βII and βIII isotypes are very prominent in the nervous system. Our previous work has suggested that βII may play a role in neuronal differentiation, but the role of βIII in neurons is not well understood. In the work reported here, we examined the roles of the different β-tubulin isotypes in response to glutamate/glycine treatment, and found that both βII and βIII bind to glutathione in the presence of ROS, especially βIII...
April 16, 2018: Cytoskeleton
https://www.readbyqxmd.com/read/29663380/transglutaminase-activity-regulates-differentiation-migration-and-fusion-of-osteoclasts-via-affecting-actin-dynamics
#5
Huifang Sun, Mari T Kaartinen
Osteoclasts, bone resorbing cells, derive from monocyte/macrophage cell lineage. Increased osteoclast activity is responsible for bone destruction in diseases such as osteoporosis, periodontitis and rheumatoid arthritis. Transglutaminases (TGs), protein crosslinking enzymes, were recently found involved in osteoclastogenesis in vivo, however their mechanisms of action have remained unknown. In this study, we have investigated the role of TG activity in osteoclastogenesis in vitro using four TG inhibitors, NC9, Z006, T101, and monodansyl cadaverine...
April 16, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29662141/the-cytoplasmic-dynein-transport-machinery-and-its-many-cargoes
#6
REVIEW
Samara L Reck-Peterson, William B Redwine, Ronald D Vale, Andrew P Carter
Cytoplasmic dynein 1 is an important microtubule-based motor in many eukaryotic cells. Dynein has critical roles both in interphase and during cell division. Here, we focus on interphase cargoes of dynein, which include membrane-bound organelles, RNAs, protein complexes and viruses. A central challenge in the field is to understand how a single motor can transport such a diverse array of cargoes and how this process is regulated. The molecular basis by which each cargo is linked to dynein and its cofactor dynactin has started to emerge...
April 16, 2018: Nature Reviews. Molecular Cell Biology
https://www.readbyqxmd.com/read/29662074/competition-between-microtubule-associated-proteins-directs-motor-transport
#7
Brigette Y Monroy, Danielle L Sawyer, Bryce E Ackermann, Melissa M Borden, Tracy C Tan, Kassandra M Ori-McKenney
Within cells, motor and non-motor microtubule-associated proteins (MAPs) simultaneously converge on the microtubule. How the binding activities of non-motor MAPs are coordinated and how they contribute to the balance and distribution of motor transport is unknown. Here, we examine the relationship between MAP7 and tau owing to their antagonistic roles in vivo. We find that MAP7 and tau compete for binding to microtubules, and determine a mechanism by which MAP7 displaces tau from the lattice. MAP7 promotes kinesin-based transport in vivo and strongly recruits kinesin-1 to the microtubule in vitro, providing evidence for direct enhancement of motor motility by a MAP...
April 16, 2018: Nature Communications
https://www.readbyqxmd.com/read/29661912/microtubule-end-tethering-of-a-processive-kinesin-8-motor-kif18b-is-required-for-spindle-positioning
#8
Toni McHugh, Agata A Gluszek, Julie P I Welburn
Mitotic spindle positioning specifies the plane of cell division during anaphase. Spindle orientation and positioning are therefore critical to ensure symmetric division in mitosis and asymmetric division during development. The control of astral microtubule length plays an essential role in positioning the spindle. In this study, using gene knockout, we show that the kinesin-8 Kif18b controls microtubule length to center the mitotic spindle at metaphase. Using in vitro reconstitution, we reveal that Kif18b is a highly processive plus end-directed motor that uses a C-terminal nonmotor microtubule-binding region to accumulate at growing microtubule plus ends...
April 16, 2018: Journal of Cell Biology
https://www.readbyqxmd.com/read/29661268/degradation-or-aggregation-the-ramifications-of-post-translational-modifications-on-tau
#9
Seoyoung Park, Jung Hoon Lee, Min Jae Lee
Tau protein is encoded in the microtubule-associated protein tau (MAPT) gene and contributes to the stability of microtubules in axons. Despite of its basic isoelectric point and high solubility, tau is often found in intraneuronal filamentous inclusions such as paired helical filaments (PHFs), which are the primary constituent of neurofibrillary tangles (NFTs). This pathological feature is the nosological entity termed "tauopathies" which notably include Alzheimer's disease (AD). A proteinaceous signature of all tauopathies is hyperphosphorylation of the accumulated tau, which has been extensively studied as a major pharmacological target for AD therapy...
April 17, 2018: BMB Reports
https://www.readbyqxmd.com/read/29660626/tubulin-posttranslational-modifications-in-in-vitro-matured-prepubertal-and-adult-ovine-oocytes
#10
E Serra, S Succu, F Berlinguer, C Porcu, G G Leoni, S Naitana, S D Gadau
Microtubules (MTs), polymers of alpha/beta-tubulin heterodimers, are involved in crucial functions in eukaryotic cells. MTs physiology can be influenced by a variety of post-translational modifications (PTMs), including tyrosination, detyrosination, delta 2 modification, acetylation, polyglutamylation, polyglycylation. In mammalian oocytes, MTs are essential for meiosis, regulating the formation of meiotic spindle and chromosomes movements. Considering that the patterns of tubulin PTMs (tyrosination, detyrosination, acetylation, polyglutamylation and delta 2 modification) have not been investigated in ovine oocytes, this study has been designed to investigate their presence and quantification in in vitro matured (IVM) adult and prepubertal ovine oocytes...
April 7, 2018: Theriogenology
https://www.readbyqxmd.com/read/29659701/gain-of-function-mutation-of-atdice1-encoding-a-putative-endoplasmic-reticulum-localized-membrane-protein-causes-defects-in-anisotropic-cell-elongation-by-disturbing-cell-wall-integrity-in-arabidopsis
#11
Phi-Yen Le, Hyung-Woo Jeon, Min-Ha Kim, Eung-Jun Park, Hyoshin Lee, Indeok Hwang, Kyung-Hwan Han, Jae-Heung Ko
Background and Aims: Anisotropic cell elongation depends on cell wall relaxation and cellulose microfibril arrangement. The aim of this study was to characterize the molecular function of AtDICE1 encoding a novel transmembrane protein involved in anisotropic cell elongation in Arabidopsis. Methods: Phenotypic characterizations of transgenic Arabidopsis plants mis-regulating AtDICE1 expression with different pharmacological treatments were made, and biochemical, cell biological and transcriptome analyses were performed...
April 5, 2018: Annals of Botany
https://www.readbyqxmd.com/read/29658943/deep-learning-massively-accelerates-super-resolution-localization-microscopy
#12
Wei Ouyang, Andrey Aristov, Mickaël Lelek, Xian Hao, Christophe Zimmer
The speed of super-resolution microscopy methods based on single-molecule localization, for example, PALM and STORM, is limited by the need to record many thousands of frames with a small number of observed molecules in each. Here, we present ANNA-PALM, a computational strategy that uses artificial neural networks to reconstruct super-resolution views from sparse, rapidly acquired localization images and/or widefield images. Simulations and experimental imaging of microtubules, nuclear pores, and mitochondria show that high-quality, super-resolution images can be reconstructed from up to two orders of magnitude fewer frames than usually needed, without compromising spatial resolution...
April 16, 2018: Nature Biotechnology
https://www.readbyqxmd.com/read/29657114/augmin-antagonizes-katanin-at-microtubule-crossovers-to-control-the-dynamic-organization-of-plant-cortical-arrays
#13
Guangda Wang, Chaofeng Wang, Weiwei Liu, Yinping Ma, Li Dong, Juan Tian, Yanjun Yu, Zhaosheng Kong
Plant cells do not possess centrosomes, which serve as the microtubule organizing center in animal cells; how plant cell microtubule arrays are established and maintain their dynamics remain poorly understood [1]. The γ-tubulin complex and the katanin complex play central roles in the organization of plant cortical microtubules [2-6]. Previously, we reported that the augmin complex recruits the γ-tubulin complex to preexisting microtubules and initiates microtubule nucleation [7]. Moreover, we described how an intricate interaction between the katanin p60 subunit KTN1 and the p80 subunit KTN80 confers precise microtubule severing at either microtubule branching nucleation sites or crossovers [8]...
April 1, 2018: Current Biology: CB
https://www.readbyqxmd.com/read/29656363/2-pentadecyl-2-oxazoline-reduces-neuroinflammatory-environment-in-the-mptp-model-of-parkinson-disease
#14
Marika Cordaro, Rosalba Siracusa, Rosalia Crupi, Daniela Impellizzeri, Alessio Filippo Peritore, Ramona D'Amico, Enrico Gugliandolo, Rosanna Di Paola, Salvatore Cuzzocrea
Current pharmacological management of Parkinson disease (PD) does not provide for disease modification, but addresses only symptomatic features. Here, we explore a new approach to neuroprotection based on the use of 2-pentadecyl-2-oxazoline (PEA-OXA), the oxazoline derivative of the fatty acid amide signaling molecule palmitoylethanolamide (PEA), in an experimental model of PD. Daily oral treatment with PEA-OXA (10 mg/kg) significantly reduced behavioral impairments and neuronal cell degeneration of the dopaminergic tract induced by four intraperitoneal injections of the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on 8-week-old male C57 mice...
April 14, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29656007/mir-195-potentiates-the-efficacy-of-microtubule-targeting-agents-in-non-small-cell-lung-cancer
#15
Xiaojie Yu, Yiqiang Zhang, Xiuye Ma, Alexander Pertsemlidis
Microtubule-targeting agents (MTAs) are widely used for the treatment of non-small cell lung cancer (NSCLC). The response rate is only ∼25%, mainly attributable to drug resistance. To identify determinants of resistance in NSCLC, we performed a high-throughput screen using a library of miRNA mimics. Here we report that miR-195 synergizes with MTAs to inhibit the growth of NSCLC cells in vitro, that increased expression of miR-195 sensitizes NSCLC cells to MTAs and that repression of miR-195 confers resistance to MTAs...
April 13, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29655610/structure-based-drug-design-and-in-vitro-metabolism-study-discovery-of-n-4-methylthiophenyl-n-2-dimethyl-cyclopenta-d-pyrimidine-as-a-potent-microtubule-targeting-agent
#16
Weiguo Xiang, Shruti Choudhary, Ernest Hamel, Susan L Mooberry, Aleem Gangjee
We report a series of tubulin targeting agents, some of which demonstrate potent antiproliferative activities. These analogs were designed to optimize the antiproliferative activity of 1 by varying the heteroatom substituent at the 4'-position, the basicity of the 4-position amino moiety, and conformational restriction. The potential metabolites of the active compounds were also synthesized. Some compounds demonstrated single digit nanomolar IC50 values for antiproliferative effects in MDA-MB-435 melanoma cells...
April 4, 2018: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/29653316/clinical-variability-and-onset-age-modifiers-in-an-extended-belgian-grn-founder-family
#17
Eline Wauters, Sara Van Mossevelde, Kristel Sleegers, Julie van der Zee, Sebastiaan Engelborghs, Anne Sieben, Rik Vandenberghe, Stéphanie Philtjens, Marleen Van den Broeck, Karin Peeters, Ivy Cuijt, Wouter De Coster, Tim Van Langenhove, Patrick Santens, Adrian Ivanoiu, Patrick Cras, Jan L De Bleecker, Jan Versijpt, Roeland Crols, Nina De Klippel, Jean-Jacques Martin, Peter P De Deyn, Marc Cruts, Christine Van Broeckhoven
We previously reported a granulin (GRN) null mutation, originating from a common founder, in multiple Belgian families with frontotemporal dementia. Here, we used data of a 10-year follow-up study to describe in detail the clinical heterogeneity observed in this extended founder pedigree. We identified 85 patients and 40 unaffected mutation carriers, belonging to 29 branches of the founder pedigree. Most patients (74.4%) were diagnosed with frontotemporal dementia, while others had a clinical diagnosis of unspecified dementia, Alzheimer's dementia or Parkinson's disease...
March 10, 2018: Neurobiology of Aging
https://www.readbyqxmd.com/read/29653082/inhibition-of-glycogen-synthase-kinase-3-reduces-extension-of-the-axonal-leading-process-by-destabilizing-microtubules-in-cerebellar-granule-neurons
#18
Yoshihiro Inami, Mitsuru Omura, Kenta Kubota, Yoshiyuki Konishi
Recent studies have uncovered various molecules that play key roles in neuronal morphogenesis. Nevertheless, the mechanisms underlying the neuron-type-dependent regulation of morphogenesis remain unknown. We have previously reported that inhibition of glycogen synthase kinase-3 (GSK3) markedly reduced axonal length of cerebellar granule neurons (CGNs) in a neuron-type-dependent manner. In the present study, we investigated the mechanisms by which the growth of CGN axons was severely suppressed upon GSK3 inhibition...
April 10, 2018: Brain Research
https://www.readbyqxmd.com/read/29652248/microtubule-assembly-governed-by-tubulin-allosteric-gain-in-flexibility-and-lattice-induced-fit
#19
Maxim Igaev, Helmut Grubmüller
Microtubules (MTs) are key components of the cytoskeleton and play a central role in cell division and development. MT assembly is known to be associated with a structural change in αβ-tubulin dimers from kinked to straight conformations. How GTP binding renders individual dimers polymerization-competent, however, is still unclear. Here, we have characterized the conformational dynamics and energetics of unassembled tubulin using atomistic molecular dynamics and free energy calculations. Contradictory to existing allosteric and lattice models, we find that GTP-tubulin favors a broad range of almost isoenergetic curvatures, whereas GDP-tubulin has a much lower bending flexibility...
April 13, 2018: ELife
https://www.readbyqxmd.com/read/29650359/asymmetric-tyrosination-of-spindle-microtubules-facilitates-selfish-inheritance
#20
Shikha Laloraya
Meiotic drive is an enigmatic process that results from biased segregation of selfish genetic elements that enhance their own transmission and drive evolution. During asymmetric female meiotic divisions, selfish elements segregate preferentially towards the egg rather than polar bodies. Recent findings demonstrate that asymmetric spindle tyrosination helps selfish elements to cheat.
April 10, 2018: Trends in Cell Biology
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