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https://www.readbyqxmd.com/read/28548923/tubb3-overexpression-has-a-negligible-effect-on-the-sensitivity-to-taxol-in-cultured-cell-lines
#1
Mihoko A Tame, Anna G Manjón, Daria Belokhvostova, Jonne A Raaijmakers, René H Medema
Microtubules are cellular targets for a variety of anticancer therapies because of their critical function in mitosis. Taxol belongs to a class of microtubule targeting agents that suppresses microtubule dynamics and interferes with the functioning of the mitotic spindle, thereby effectively blocking cell cycle progression of rapidly proliferating tumor cells. Despite its antitumor activity, drug resistance remains a common obstacle in improving its overall clinical efficacy. Previous studies have shown that the expression of a specific β-tubulin isotype, βIII-tubulin/TUBB3, is dysregulated in drug-refractory tumors...
May 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28548902/er-mitochondria-signaling-regulates-autophagy
#2
Patricia Gomez-Suaga, Sebastien Paillusson, Christopher C J Miller
The endoplasmic reticulum (ER) and mitochondria form tight functional contacts that regulate a number of key cellular processes. The formation of these contacts involves "tethering proteins" that function to recruit regions of ER to mitochondria. The integral ER protein VAPB (VAMP associated protein B and C) binds to the outer mitochondrial membrane protein, RMDN3/PTPIP51 (regulator of microtubule dynamics 3) to form one such set of tethers. Recently, we showed that the VAPB-RMDN3 tethers regulate macroautophagy/autophagy...
May 26, 2017: Autophagy
https://www.readbyqxmd.com/read/28548701/microtubules-regulate-brush-border-formation
#3
Facundo M Tonucci, Anabela Ferretti, Evangelina Almada, Pamela Cribb, Rodrigo Vena, Florencia Hidalgo, Cristián Favre, Matt J Tyska, Irina Kaverina, M Cecilia Larocca
Most epithelial cells contain apical membrane structures associated to bundles of actin filaments, which constitute the brush border. Whereas microtubule participation in the maintenance of the brush border identity has been characterized, their contribution to de novo microvilli organization remained elusive. Hereby, using a cell model of individual enterocyte polarization, we found that nocodazole induced microtubule depolymerization prevented the de novo brush border formation. Microtubule participation in brush border actin organization was confirmed in polarized kidney tubule MDCK cells...
May 26, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28548285/neonatal-hypoxia-ischemia-in-rat-increases-doublecortin-concentration-in-the-cerebrospinal-fluid
#4
Catherine Brégère, Urs Fisch, Martin H Sailer, Wolfgang S Lieb, Laurie Chicha, Fabienne Goepfert, Thomas Kremer, Raphael Guzman
Doublecortin (DCX) is a microtubule-associated protein widely used as an indicator of neurogenesis in immunohistochemical analyses of the postmortem adult brain. A recent study reported that DCX can be quantified in the cerebrospinal fluid (CSF) from healthy rats between postnatal day 0 (P0) and P30. However, it is currently unclear whether the concentration of DCX in the CSF (CSF-DCX) may represent a measure of endogenous neurogenesis. To address this question, the present study examined the impact of a neonatal hypoxic-ischemic (HI) brain injury, known to induce neurogenesis, on CSF-DCX...
May 26, 2017: European Journal of Neuroscience
https://www.readbyqxmd.com/read/28547002/oncolytic-herpes-simplex-virus-inhibits-pediatric-brain-tumor-migration-and-invasion
#5
Julia V Cockle, Anke Brüning-Richardson, Karen J Scott, Jill Thompson, Timothy Kottke, Ewan Morrison, Azam Ismail, Angel M Carcaboso, Ailsa Rose, Peter Selby, Joe Conner, Susan Picton, Susan Short, Richard Vile, Alan Melcher, Elizabeth Ilett
Pediatric high-grade glioma (pHGG) and diffuse intrinsic pontine glioma (DIPG) are invasive tumors with poor survival. Oncolytic virotherapy, initially devised as a direct cytotoxic treatment, is now also known to act via immune-mediated mechanisms. Here we investigate a previously unreported mechanism of action: the inhibition of migration and invasion in pediatric brain tumors. We evaluated the effect of oncolytic herpes simplex virus 1716 (HSV1716) on the migration and invasion of pHGG and DIPG both in vitro using 2D (scratch assay, live cell imaging) and 3D (spheroid invasion in collagen) assays and in vivo using an orthotopic xenograft model of DIPG invasion...
June 16, 2017: Molecular Therapy Oncolytics
https://www.readbyqxmd.com/read/28546446/mechanisms-mitigating-problems-with-multiple-kinetochores-on-one-microtubule-in-early-mitosis
#6
Zuojun Yue, Shinya Komoto, Marek Gierlinski, Debora Pasquali, Etsushi Kitamura, Tomoyuki U Tanaka
Proper chromosome segregation in mitosis relies on correct kinetochore interaction with spindle microtubules. In early mitosis, each kinetochore usually interacts with the lateral side of each microtubule and is subsequently tethered at the microtubule end. However, since eukaryotic cells carry multiple chromosomes, multiple kinetochores could occasionally interact with a single microtubule. The consequence of this is unknown. Here we find that, although two kinetochores (two pairs of sister kinetochores) can interact with the lateral side of one microtubule, only one kinetochore can form sustained attachment to the microtubule end in budding yeast...
May 25, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28545672/enhancement-of-apoptotic-activities-on-brain-cancer-cells-via-the-combination-of-%C3%AE-tocotrienol-and-jerantinine-a
#7
Ibrahim Babangida Abubakar, Kuan-Hon Lim, Toh-Seok Kam, Hwei-San Loh
BACKGROUND: γ-Tocotrienol, a vitamin E isomer possesses pronounced in vitro anticancer activities. However, the in vivo potency has been limited by hardly achievable therapeutic levels owing to inefficient high-dose oral delivery which leads to subsequent metabolic degradation. Jerantinine A, an Aspidosperma alkaloid, originally isolated from Tabernaemontana corymbosa, has proved to possess interesting anticancer activities. However, jerantinine A also induces toxicity to non-cancerous cells...
July 1, 2017: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/28545186/gallium-nanoparticle-mediated-reduction-of-brain-specific-serine-protease-4-in-an-experimental-metastatic-cancer-model
#8
Enas M Moustafa, Marwa Abdelhameed Mohamed, Noura M Thabet
Purpose: Tumor growth and metastasis depend on angiogenesis; therefore, efforts are being made to develop specific angiogenic inhibitors. Gallium (Ga) is the second most common metal ion, after platinum, used in cancer treatment. Its activities are numerous and various. In the present study, we aimed to investigate the effect of Ga on brain metastasis arising from hepatocellular carcinoma (HCC). Materials and methods: Forty experimental rats (divided into 4 groups) received diethylnitrosamine (DEN) at a dose (20 mg/kg...
April 1, 2017: Asian Pacific Journal of Cancer Prevention: APJCP
https://www.readbyqxmd.com/read/28545020/microtubule-inhibitor-sp-6-27-inhibits-angiogenesis-and-induces-apoptosis-in-ovarian-cancer-cells
#9
Arpita Kulshrestha, Gajendra K Katara, Safaa A Ibrahim, Renukadevi Patil, Shivaputra A Patil, Kenneth D Beaman
In ovarian cancer (OVCA), treatment failure due to chemo-resistance is a serious challenge. It is therefore critical to identify new therapies that are effective against resistant tumors and have reduced side effects. We recently identified 4-H-chromenes as tubulin depolymerizing agents that bind to colchicine site of beta-tubulin. Here, we screened a chemical library of substituted 4-H-chromenes and identified SP-6-27 to exhibit most potent anti-proliferative activity towards a panel of human cisplatin sensitive and resistant OVCA cell lines with 50% inhibitory concentration (IC50; mean ± SD) ranging from 0...
May 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28542137/dt-13-synergistically-enhanced-vinorelbine-mediated-mitotic-arrest-through-inhibition-of-foxm1-bicd2-axis-in-non-small-cell-lung-cancer-cells
#10
Hongyang Li, Li Sun, Hang Li, Xiaodan Lv, Herve Semukunzi, Ruiming Li, Jun Yu, Shengtao Yuan, Sensen Lin
Non-small-cell lung cancer (NSCLC) is the most commonly diagnosed malignant disease with the leading cause of cancer-related death. Combination treatment remains the major strategy in the clinical therapy of NSCLC. Vinorelbine (NVB), a semi-synthetic vinca alkaloid, is used for advanced and metastatic NSCLC by destabilizing microtubule formation to induce mitotic arrest and cell death. However, the side effect of NVB heavily affected its effectiveness in clinical therapy. Hence, it is of great significance to develop new agents to synergize with NVB and decrease the adverse effect...
May 25, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28541657/chemical-modulation-of-protein-o-glcnacylation-via-ogt-inhibition-promotes-human-neural-cell-differentiation
#11
Lissette M Andres, Ian W Blong, Angela C Evans, Neil G Rumachik, Teppei Yamaguchi, Nam D Pham, Pamela Thompson, Jennifer J Kohler, Carolyn R Bertozzi
The enzymes that determine protein O-GlcNAcylation, O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA), act on key transcriptional and epigenetic regulators and both are abundantly expressed in the brain. However, little is known about how alterations in O-GlcNAc cycling affect human embryonic stem cell (hESC) neural differentiation. Here, we studied the effects of perturbing O-GlcNAcylation during neural induction of hESCs using the metabolic inhibitor of OGT, peracetylated 5-thio-N-acetylglucosamine (Ac4-5SGlcNAc)...
May 25, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28541346/acf7-regulates-inflammatory-colitis-and-intestinal-wound-response-by-orchestrating-tight-junction-dynamics
#12
Yanlei Ma, Jiping Yue, Yao Zhang, Chenzhang Shi, Matt Odenwald, Wenguang G Liang, Qing Wei, Ajay Goel, Xuewen Gou, Jamie Zhang, Shao-Yu Chen, Wei-Jen Tang, Jerrold R Turner, Feng Yang, Hong Liang, Huanlong Qin, Xiaoyang Wu
In the intestinal epithelium, the aberrant regulation of cell/cell junctions leads to intestinal barrier defects, which may promote the onset and enhance the severity of inflammatory bowel disease (IBD). However, it remains unclear how the coordinated behaviour of cytoskeletal network may contribute to cell junctional dynamics. In this report, we identified ACF7, a crosslinker of microtubules and F-actin, as an essential player in this process. Loss of ACF7 leads to aberrant microtubule organization, tight junction stabilization and impaired wound closure in vitro...
May 25, 2017: Nature Communications
https://www.readbyqxmd.com/read/28540657/uch-l1-inhibition-suppresses-tau-aggresome-formation-during-proteasomal-impairment
#13
Quntao Yu, Hongmao Zhang, Yuan Li, Chao Liu, Shaohui Wang, Xiaomei Liao
In conditions of proteasomal impairment, the damaged or misfolded proteins, collectively known as aggresome, can accumulate in the perinuclear space and be subsequently eliminated by autophagy. Abnormal aggregation of microtubule-associated protein tau in the cytoplasm is a common neuropathological feature of tauopathies. The deficiency in ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), a proteasomal deubiquitinating enzyme, is closely related to tau aggregation; however, the associated mechanisms remain unclear...
May 24, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28540373/in-vitro-cellular-behaviors-and-toxicity-assays-of-small-sized-fluorescent-silicon-nanoparticles
#14
Zhaohui Cao, Fei Peng, Zhilin Hu, Binbin Chu, Yiling Zhong, Yuanyuan Su, Sudan He, Yao He
Extensive investigations have been carried out for evaluating the toxicology of various nanomaterials (e.g., carbon- and metal-based nanomaterials), which offer invaluable information for assessing the feasibility of nanomaterial-based wide-ranging applications. In recent years, sufficient efforts have been made to develop fluorescent small-sized silicon nanoparticles (SiNPs) as a novel optical material simultaneously featuring strong fluorescence and ultrahigh photostability, providing high promise for a myriad of biological, biomedical and electronic applications...
May 25, 2017: Nanoscale
https://www.readbyqxmd.com/read/28538724/applying-systems-level-spectral-imaging-and-analysis-to-reveal-the-organelle-interactome
#15
Alex M Valm, Sarah Cohen, Wesley R Legant, Justin Melunis, Uri Hershberg, Eric Wait, Andrew R Cohen, Michael W Davidson, Eric Betzig, Jennifer Lippincott-Schwartz
The organization of the eukaryotic cell into discrete membrane-bound organelles allows for the separation of incompatible biochemical processes, but the activities of these organelles must be coordinated. For example, lipid metabolism is distributed between the endoplasmic reticulum for lipid synthesis, lipid droplets for storage and transport, mitochondria and peroxisomes for β-oxidation, and lysosomes for lipid hydrolysis and recycling. It is increasingly recognized that organelle contacts have a vital role in diverse cellular functions...
May 24, 2017: Nature
https://www.readbyqxmd.com/read/28537927/wx-132-18b-a-novel-microtubule-inhibitor-exhibits-promising-anti-tumor-effects
#16
Fang Guan, Rui Ding, Qi Zhang, Wei Chen, Feifei Li, Long Long, Wei Li, Linna Li, Dexuan Yang, Lan Xie, Shoujun Yuan, Lili Wang
Cancer drug researchers have been seeking microtubule-inhibiting agents (MIAs) with higher bioactivity and lower toxicity than currently marketed drugs. WX-132-18B, a novel structural compound synthesized at our institute, specifically bound to the colchicine-binding site on tubulin rather than the vinblastine site, and concentration-dependently reduced microtubule content via depolymerization. It exhibited the same cellular phenotypic profiles as the classic MIAs (colchicine, vincristine, and taxol), including inducing cell cycle arrest at the G2/M phase, triggering tumor cell apoptosis, promoting nuclear membrane permeability, reducing mitochondrial membrane potential, and disrupting the redox system balance...
May 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28537848/influence-of-endurance-training-on-skeletal-muscle-mitophagy-regulatory-proteins-in-type-2-diabetic-men
#17
Christian Brinkmann, Axel Przyklenk, Alexander Metten, Thorsten Schiffer, Wilhelm Bloch, Klara Brixius, Sebastian Gehlert
BACKGROUND: Mitophagy is a form of autophagy for the elimination of mitochondria. Mitochondrial content and function are reduced in the skeletal muscle of patients with type 2 diabetes mellitus (T2DM). Physical training has been shown to restore mitochondrial capacity in T2DM patients, but the role of mitophagy has not been examined in this context. This study analyzes the impact of a 3-month endurance training on important skeletal muscle mitophagy regulatory proteins and oxidative phosphorylation (OXPHOS) complexes in T2DM patients...
May 24, 2017: Endocrine Research
https://www.readbyqxmd.com/read/28537258/exploiting-the-kinesin-1-molecular-motor-to-generate-a-virus-membrane-penetration-site
#18
Madhu Sudhan Ravindran, Martin F Engelke, Kristen J Verhey, Billy Tsai
Viruses exploit cellular machineries to penetrate a host membrane and cause infection, a process that remains enigmatic for non-enveloped viruses. Here we probe how the non-enveloped polyomavirus SV40 penetrates the endoplasmic reticulum (ER) membrane to reach the cytosol, a crucial infection step. We find that the microtubule-based motor kinesin-1 is recruited to the ER membrane by binding to the transmembrane J-protein B14. Strikingly, this motor facilitates SV40 ER-to-cytosol transport by constructing a penetration site on the ER membrane called a 'focus'...
May 24, 2017: Nature Communications
https://www.readbyqxmd.com/read/28536471/caffeic-acid-attenuates-diabetic-kidney-disease-via-modulation-of-autophagy-in-a-high-fat-diet-streptozotocin-induced-diabetic-rat
#19
Marwa Matboli, Sanaa Eissa, Doaa Ibrahim, Marwa G A Hegazy, Shalabia S Imam, Eman K Habib
The aim of this study is to evaluate the anti-diabetic nephropathy effect of Caffeic acid and to prove our hypothesis for its mechanism of action that it may occur by reactivation of autophagy pathway via suppression of autophagy regulatory miRNAs. In vivo, high-fat diet and streptozotocin-induced (HFD-STZ) diabetic rats were treated with Caffeic acid once per day for 12 weeks before and after development of diabetic nephropathy. Blood and urine biochemical parameters, autophagy transcripts and their epigenetic regulators together with renal tissue morphology were investigated...
May 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28536263/axodendritic-sorting-and-pathological-missorting-of-tau-is-isoform-specific-and-determined-by-axon-initial-segment-architecture
#20
Hans Zempel, Frank Dennissen, Yatender Kumar, Julia Luedtke, Jacek Biernat, Eva-Maria Mandelkow, Eckhard Mandelkow
Subcellular mislocalization of the microtubule-associated protein Tau is a hallmark of Alzheimer disease (AD) and other tauopathies. Six Tau isoforms, differentiated by the presence or absence of a second repeat or of N-terminal inserts, exist in the human CNS but their physiological and pathological differences have long remained remain elusive. Here, we investigated the properties and distributions of human and rodent Tau isoforms in primary forebrain rodent neurons. We found that the Tau-Diffusion-Barrier (TDB), located within the Axon-Initial-Segment (AIS), controls retrograde (axon-to-soma) and anterograde (soma-to-axon) traffic of Tau...
May 23, 2017: Journal of Biological Chemistry
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