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https://www.readbyqxmd.com/read/28320103/paeoniflorin-ameliorates-ages-induced-mesangial-cell-injury-through-inhibiting-rage-mtor-autophagy-pathway
#1
Juan Chen, Di Zhao, Maomao Zhu, Minghua Zhang, Xuefeng Hou, Wenbo Ding, Shuai Sun, Weiquan Bu, Liang Feng, Shiping Ma, Xiaobin Jia
Glomerular mesangial cell plays a vital role in diabetic nephropathy (DN). Recent research has demonstrated that autophagy involved in the development of DN. Paeoniflorin (PF), a monoterpene glucoside, has been proved to attenuate advanced glycation end products (AGEs)-induced mesangial cell injury. However, the regulatory mechanism of PF on autophagy in mesangial cell remains unclear. The aim of this study was to explore the effect of PF on autophagy in AGEs-induced mesangial cell dysfunction. In this study, the leakage of the lactic dehydrogenase (LDH) into the extracellular medium was measured by LDH kit...
March 18, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28319390/qualitative-behavior-of-the-low-frequency-vibrational-dynamics-of-microtubules-and-the-surrounding-water
#2
Jeremy M Moix, James E Parker, Ibtissam Echchgadda
The dynamics of the low-frequency vibrational modes of microtubules play a key role in many theoretical models regarding their biological function. We analyze these dynamics through large scale, classical molecular dynamics simulations of a microtubule composed of 42 tubulin heterodimers to provide insights into the qualitative nature of the vibrational energy absorption and dissipation mechanisms. The computed microtubule absorption spectra and vibrational density of states in the terahertz regime are presented, along with an analysis of the vibrational dephasing rates of the tubulin monomer center of mass dynamics, which are shown to be overdamped...
March 20, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/28319065/the-drebrin-eb3-pathway-drives-invasive-activity-in-prostate-cancer
#3
A E Dart, D C Worth, G Muir, A Chandra, J D Morris, C McKee, C Verrill, R J Bryant, P R Gordon-Weeks
Prostate cancer is the most common cancer in men and the metastatic form of the disease is incurable. We show here that the drebrin/EB3 pathway, which co-ordinates dynamic microtubule/actin filament interactions underlying cell shape changes in response to guidance cues, plays a role in prostate cancer cell invasion. Drebrin expression is restricted to basal epithelial cells in benign human prostate but is upregulated in luminal epithelial cells in foci of prostatic malignancy. Drebrin is also upregulated in human prostate cancer cell lines and co-localizes with actin filaments and dynamic microtubules in filopodia of pseudopods of invading cells under a chemotactic gradient of the chemokine CXCL12...
March 20, 2017: Oncogene
https://www.readbyqxmd.com/read/28318980/cell-specific-%C3%AE-tubulin-isotype-regulates-ciliary-microtubule-ultrastructure-intraflagellar-transport-and-extracellular-vesicle-biology
#4
Malan Silva, Natalia Morsci, Ken C Q Nguyen, Anza Rizvi, Christopher Rongo, David H Hall, Maureen M Barr
Cilia are found on most non-dividing cells in the human body and, when faulty, cause a wide range of pathologies called ciliopathies. Ciliary specialization in form and function is observed throughout the animal kingdom, yet mechanisms generating ciliary diversity are poorly understood. The "tubulin code"-a combination of tubulin isotypes and tubulin post-translational modifications-can generate microtubule diversity. Using C. elegans, we show that α-tubulin isotype TBA-6 sculpts 18 A- and B-tubule singlets from nine ciliary A-B doublet microtubules in cephalic male (CEM) neurons...
March 8, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/28318914/systemic-and-network-functions-of-the-microtubule-associated-protein-tau-implications-for-tau-based-therapies
#5
REVIEW
Lidia Bakota, Abdala Ussif, Gunnar Jeserich, Roland Brandt
Tau is a microtubule-associated neuronal protein, whose primary role was long thought to regulate axonal microtubule assembly. Tau is subject to many posttranslational modifications and can aggregate into neurofibrillary tangles, which are considered to be a hallmark of several neurodegenerative diseases collectively called "tauopathies". The most common tauopathy is Alzheimer's disease, where tau pathology correlates with sites of neurodegeneration. Tau belongs to the class of intrinsically disordered proteins, which are known to interact with many partners and are considered to be involved in various signaling, regulation and recognition processes...
March 16, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/28317275/synthesis-of-%C3%AE-tubulin-occurs-within-chromatoid-body-of-round-spermatids
#6
Yuki Fujii, Hideaki Fujita, Sadaki Yokota
mRNAs for proteins required in elongated spermatids are considered to be transcribed at an early stage and stored in cytoplasm, presumably in chromatoid body (CB), one type of nuage component (a unique structure that appears and disappears during spermatogenesis), because transcription of genes does not occur at late stages. In elongated spermatids, a large amount of tubulin molecules is required to form microtubules of manchette and flagellum. To investigate the possible role of CB in translation of tubulin mRNA, we performed immunofluorescence and immunoelectron microscopic localization studies of α- and β-tubulin in rat spermatogenic cells...
March 20, 2017: Cytoskeleton
https://www.readbyqxmd.com/read/28317260/comparative-proteomic-analysis-of-trophoblast-cell-models-reveals-their-differential-phenotypes-potential-uses-and-limitations
#7
Paulina B Szklanna, Kieran Wynne, Marie Nolan, Karl Egan, Fionnuala Ní Áinle, Patricia B Maguire
Trophoblastic cell lines are widely used in in vitro studies of placental function as a surrogate for primary trophoblasts. To date, no reference proteomics dataset exists to directly compare the shared and unique characteristics of these cells. Here, we performed comparative proteomic profiling of the BeWo and HTR8/SVneo cell lines using label-free quantitative mass spectrometry. 1557 proteins were identified, which included 338 uniquely attributed to BeWo cells, and a further 304 specifically identified in HTR8/SVneo cells...
March 20, 2017: Proteomics
https://www.readbyqxmd.com/read/28317021/the-bloc-1-subunit-pallidin-facilitates-activity-dependent-synaptic-vesicle-recycling
#8
Xun Chen, Wenpei Ma, Shixing Zhang, Jeremy Paluch, Wanlin Guo, Dion K Dickman
Membrane trafficking pathways must be exquisitely coordinated at synaptic terminals to maintain functionality, particularly during conditions of high activity. We have generated null mutations in the Drosophila homolog of pallidin, a central subunit of the biogenesis of lysosome-related organelles complex-1 (BLOC-1), to determine its role in synaptic development and physiology. We find that Pallidin localizes to presynaptic microtubules and cytoskeletal structures, and that the stability of Pallidin protein is highly dependent on the BLOC-1 components Dysbindin and Blos1...
January 2017: ENeuro
https://www.readbyqxmd.com/read/28316159/-mechanism-of-angiotensin-converting-enzyme-2-overexpression-improving-collagen-synthesis-in-lung
#9
Q J Yang, B B Zheng, N N Sun, M X Pan, Z M Zheng, Y Meng
Objective: To explore the mechanism of angiotensin-converting enzyme 2 (ACE2) overexpression improving collagen synthesis in lung. Methods: Lung fibroblasts of mice over-expressing ACE2 and the wild type (WT) were cultured in vitro and divided into 5 groups: WT-control, WT-AngiotensinⅡ (AngⅡ), ACE2(+ /+) -control, ACE2(+ /+) -AngⅡ and ACE2(+ /+) -AngⅡ+ A779. The protein relative expression levels of ACE2, collagen Ⅰ, nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4), nucleotide binding and oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3), autophagy-related protein (Beclin1), ubiquitin-binding protein p62 (P62), microtubule-associated proteins light chain 3-Ⅱ (LC3-Ⅱ) were measured by Western blot and triphosadenine (ATP) level was measured by ATP Assay Kit...
March 14, 2017: Zhonghua Yi Xue za Zhi [Chinese medical journal]
https://www.readbyqxmd.com/read/28315956/axonal-transport-deficits-in-multiple-sclerosis-spiraling-into-the-abyss
#10
REVIEW
Robert van den Berg, Casper C Hoogenraad, Rogier Q Hintzen
The transport of mitochondria and other cellular components along the axonal microtubule cytoskeleton plays an essential role in neuronal survival. Defects in this system have been linked to a large number of neurological disorders. In multiple sclerosis (MS) and associated models such as experimental autoimmune encephalomyelitis (EAE), alterations in axonal transport have been shown to exist before neurodegeneration occurs. Genome-wide association (GWA) studies have linked several motor proteins to MS susceptibility, while neuropathological studies have shown accumulations of proteins and organelles suggestive for transport deficits...
March 18, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28315173/ricolinostat-a-selective-hdac6-inhibitor-shows-anti-lymphoma-cell-activity-alone-and-in-combination-with-bendamustine
#11
Maria Cosenza, Monica Civallero, Luigi Marcheselli, Stefano Sacchi, Samantha Pozzi
Histone deacetylase inhibitors (HDACis) have emerged as a new class of anticancer agents, targeting the biological process including cell cycle and apoptosis. We investigated and explained the anticancer effects of an HDAC6 inhibitor, ricolinostat alone and in combination with bendamustine in lymphoma cell lines. Cell viability was measured by MTT assay. Apoptosis, reactive oxygen species (ROS) generation, Bcl-2 protein expression, cell cycle progression and tubuline expression were determined by flow cytometry...
March 17, 2017: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/28314794/the-microtubule-associated-protein-map18-affects-rop2-gtpase-activity-during-root-hair-growth
#12
Erfang Kang, Mingzhi Zheng, Yan Zhang, Ming Yuan, Shaul Yalovsky, Lei Zhu, Ying Fu
Establishment and maintenance of the polar site are important for root hair tip growth. We previously reported that Arabidopsis (Arabidopsis thaliana) MICROTUBULE-ASSOCIATED PROTEIN18 (MAP18) functions in controlling the direction of pollen tube growth and root hair elongation. Additionally, the Rop GTPase ROP2 was reported as a positive regulator of both root hair initiation and tip growth in Arabidopsis. Both loss-of-function of ROP2 or knock-down of MAP18 leads to a decrease in root hair length, whereas overexpression of either MAP18 or ROP2 causes multiple tips or a branching hair phenotype...
March 17, 2017: Plant Physiology
https://www.readbyqxmd.com/read/28314741/an-engineered-minimal-chromosomal-passenger-complex-reveals-a-role-for-incenp-sli15-spindle-association-in-chromosome-biorientation
#13
Sarah Fink, Kira Turnbull, Arshad Desai, Christopher S Campbell
The four-subunit chromosomal passenger complex (CPC), whose enzymatic subunit is Aurora B kinase, promotes chromosome biorientation by detaching incorrect kinetochore-microtubule attachments. In this study, we use a combination of truncations and artificial dimerization in budding yeast to define the minimal CPC elements essential for its biorientation function. We engineered a minimal CPC comprised of the dimerized last third of the kinase-activating Sli15/INCENP scaffold and the catalytic subunit Ipl1/Aurora B...
March 17, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28314740/dual-recognition-of-chromatin-and-microtubules-by-incenp-is-important-for-mitotic-progression
#14
Michael S Wheelock, David J Wynne, Boo Shan Tseng, Hironori Funabiki
The chromosomal passenger complex (CPC), composed of inner centromere protein (INCENP), Survivin, Borealin, and the kinase Aurora B, contributes to the activation of the mitotic checkpoint. The regulation of CPC function remains unclear. Here, we reveal that in addition to Survivin and Borealin, the single α-helix (SAH) domain of INCENP supports CPC localization to chromatin and the mitotic checkpoint. The INCENP SAH domain also mediates INCENP's microtubule binding, which is negatively regulated by Cyclin-dependent kinase-mediated phosphorylation of segments flanking the SAH domain...
March 17, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28303942/signature-of-an-aggregation-prone-conformation-of-tau
#15
Neil A Eschmann, Elka R Georgieva, Pritam Ganguly, Peter P Borbat, Maxime D Rappaport, Yasar Akdogan, Jack H Freed, Joan-Emma Shea, Songi Han
The self-assembly of the microtubule associated tau protein into fibrillar cell inclusions is linked to a number of devastating neurodegenerative disorders collectively known as tauopathies. The mechanism by which tau self-assembles into pathological entities is a matter of much debate, largely due to the lack of direct experimental insights into the earliest stages of aggregation. We present pulsed double electron-electron resonance measurements of two key fibril-forming regions of tau, PHF6 and PHF6*, in transient as aggregation happens...
March 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28302912/intraflagellar-transport-protein-ift52-recruits-ift46-to-the-basal-body-and-flagella
#16
Bo Lv, Lei Wan, Michael Taschner, Xi Cheng, Esben Lorentzen, Kaiyao Huang
Cilia are microtubule based organelles and perform motile, sensing and signaling functions. The assembly and maintenance of cilia depend on intraflagellar transport. Besides ciliary localization, most IFT proteins accumulate at basal bodies. However, little is known about the molecular mechanism of basal body targeting of IFT proteins. We first identified the possible basal body targeting sequence of IFT46 by expressing IFT46 truncations in ift46-1 mutant. The C-terminal sequence 246-321 aa, termed BBTS3, was sufficient to target YFPs to basal bodies in ift46-1 Interestingly, BBTS3 is also responsible for the ciliary targeting of IFT46...
March 16, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28302908/tubulin-isotype-substitution-revealed-that-isotype-composition-modulates-microtubule-dynamics-in-c-elegans-embryos
#17
Yu Honda, Kenta Tsuchiya, Eisuke Sumiyoshi, Nami Haruta, Asako Sugimoto
Microtubules (MTs) are polymers composed of α- and β-tubulin heterodimers, which are generally encoded by multiple gene loci. Despite implications of distinct properties of isotypes, how they contribute to diverse MT dynamics in vivo remains unclear. Here, using genome editing and RNAi depletion of tubulin isotypes, we demonstrate that four tubulin isotypes (hereafter α1, α2, β1 and β2) cooperatively confer distinct MT properties in Caenorhabditis elegans early embryos. GFP insertion into each isotype locus reveals their distinct expression levels and MT incorporation rates...
March 16, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28302907/skip-controls-lysosome-positioning-using-a-composite-kinesin-1-heavy-and-light-chain-binding-domain
#18
Anneri Sanger, Yan Y Yip, Thomas S Randall, Stefano Pernigo, Roberto A Steiner, Mark P Dodding
The molecular interplay between cargo recognition and regulation of the activity of the kinesin-1 microtubule motor is not well understood. Using the lysosome adaptor SKIP as model cargo, we show that the heavy chains (KHCs), in addition to the light chains (KLCs), can recognize tryptophan-acidic binding determinants on the cargo when presented in the context of an extended KHC interacting domain. Mutational separation of KHC and KLC binding shows that both interactions are important for SKIP-kinesin-1 interaction in vitro and that KHC binding is important for lysosome transport in vivo...
March 16, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28301815/synthesis-and-biological-evaluation-of-novel-podophyllotoxin-nsaids-conjugates-as-multifunctional-anti-mdr-agents-against-resistant-human-hepatocellular-carcinoma-bel-7402-5-fu-cells
#19
Lei Zhang, Lai Liu, Chengyue Zheng, Yang Wang, Xuqiang Nie, Dabin Shi, Yongzheng Chen, Gang Wei, Jing Wang
Currently, multi-drug resistance (MDR) to chemotherapy agents is a major hindrance to the treatment of hepatocellular carcinoma. Development of novel antineoplastic drug with anti-MDR activity is an effectively way to overcome cancer resistance. In present study, novel podophyllotoxin-NSAIDs conjugates were synthesized, and their antiproliferative activities were evaluated in vitro. The most potent conjugate, A1, displayed selective cytotoxicity against resistant Bel-7402/5-FU cells with an IC50 value of 0...
March 8, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28300595/a-biophysical-model-of-how-%C3%AE-tubulin-carboxy-terminal-tails-tune-kinesin-1-processivity-along-microtubule
#20
Miljko V Sataric, Dalibor L Sekulic, Slobodan Zdravkovic, Nebojsa M Ralevic
It appears that so-called post-translational modifications of tubulin heterodimers are mostly focussed at positions of amino acid sequences of carboxy-terminal tails. These changes have very profound effects on microtubule functions especially in connection with cellular traffic in terms of motor proteins. In this study, we elaborated the biophysical model aimed to explain the strategy governing these subtle interplays between structural and functional properties of microtubules. We relied onto Langevin equations including fluctuation-dissipation processes...
March 12, 2017: Journal of Theoretical Biology
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