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https://www.readbyqxmd.com/read/28545186/gallium-nanoparticle-mediated-reduction-of-brain-specific-serine-protease-4-in-an-experimental-metastatic-cancer-model
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
https://www.readbyqxmd.com/read/28536143/aurora-kinase-a-promotes-ar-degradation-via-the-e3-ligase-chip
#14
James M Larner, Sukumar Sarkar, David L Brautigan
Reducing the levels of the androgen receptor (AR) is one of the most viable approaches to combat castration-resistant prostate cancer (CRPC). Previously, we observed that proteasomal-dependent degradation of AR in response to 2-methoxyestradiol (2-ME) depends primarily on the E3 ligase C-terminus of HSP70-interacting protein (STUB1/CHIP). Here, 2-ME stimulation activates CHIP by phosphorylation via Aurora kinase A (AURKA). Aurora A kinase inhibitors and RNAi knockdown of Aurora A transcript selectively blocked CHIP phosphorylation and AR degradation...
May 23, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28536121/spindle-assembly-checkpoint-satisfaction-occurs-via-end-on-but-not-lateral-attachments-under-tension
#15
Jonathan Kuhn, Sophie Dumont
To ensure accurate chromosome segregation, the spindle assembly checkpoint (SAC) prevents anaphase until all kinetochores attach to the spindle. What signals the SAC monitors remains unclear. We do not know the contributions of different microtubule attachment features or tension from biorientation to SAC satisfaction nor how these possible cues change during attachment. In this study, we quantify concurrent Mad1 intensity and report on SAC silencing, real-time attachment geometry, occupancy, and tension at individual mammalian kinetochores...
May 23, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28536070/cotinine-improves-visual-recognition-memory-and-decreases-cortical-tau-phosphorylation-in-the-tg6799-mice
#16
J Alex Grizzell, Sagar Patel, George E Barreto, Valentina Echeverria
Alzheimer's disease (AD) is associated with the progressive aggregation of hyperphosphorylated forms of the microtubule associated protein Tau in the central nervous system. Cotinine, the main metabolite of nicotine, reduced working memory deficits, synaptic loss, and amyloid β peptide aggregation into oligomers and plaques as well as inhibited the cerebral Tau kinase, glycogen synthase 3β (GSK3β) in the transgenic (Tg)6799 (5XFAD) mice. In this study, the effect of cotinine on visual recognition memory and cortical Tau phosphorylation at the GSK3β sites Serine (Ser)-396/Ser-404 and phospho-CREB were investigated in the Tg6799 and non-transgenic (NT) littermate mice...
May 20, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/28535980/nogo-receptor-1-antagonization-in-combination-with-neurotrophin-4-5-is-not-superior-to-single-factor-treatment-in-promoting-survival-and-morphological-complexity-of-cultured-dopaminergic-neurons
#17
Stefanie Seiler, Stefano Di Santo, Sebastian Sahli, Lukas Andereggen, Hans Rudolf Widmer
Cell transplantation using ventral mesencephalic tissue is an experimental approach to treat Parkinson's disease. This approach is limited by poor survival of the transplants and the high number of dopaminergic neurons needed for grafting. Increasing the yield of dopaminergic neurons in donor tissue is of great importance. We have previously shown that antagonization of the Nogo-receptor 1 by NEP1-40 promoted survival of cultured dopaminergic neurons and exposure to neurotrophin-4/5 increased dopaminergic cell densities in organotypic midbrain cultures...
May 20, 2017: Brain Research
https://www.readbyqxmd.com/read/28535377/mechanism-of-ska-recruitment-by-ndc80-complexes-to-kinetochores
#18
Paweł Ł Janczyk, Katarzyna A Skorupka, John G Tooley, Daniel R Matson, Cortney A Kestner, Thomas West, Owen Pornillos, P Todd Stukenberg
Yeast use the ring-shaped Dam1 complex to slide down depolymerizing microtubules to move chromosomes, but current models suggest that other eukaryotes do not have a sliding ring. We visualized Ndc80 and Ska complexes on microtubules by electron microscopic tomography to identify the structure of the human kinetochore-microtubule attachment. Ndc80 recruits the Ska complex so that the V shape of the Ska dimer interacts along protofilaments. We identify a mutant of the Ndc80 tail that is deficient in Ska recruitment to kinetochores and in orienting Ska along protofilaments in vitro...
May 22, 2017: Developmental Cell
https://www.readbyqxmd.com/read/28535376/dephosphorylation-of-the-ndc80-tail-stabilizes-kinetochore-microtubule-attachments-via-the-ska-complex
#19
Dhanya K Cheerambathur, Bram Prevo, Neil Hattersley, Lindsay Lewellyn, Kevin D Corbett, Karen Oegema, Arshad Desai
During cell division, genome inheritance is orchestrated by microtubule attachments formed at kinetochores of mitotic chromosomes. The primary microtubule coupler at the kinetochore, the Ndc80 complex, is regulated by Aurora kinase phosphorylation of its N-terminal tail. Dephosphorylation is proposed to stabilize kinetochore-microtubule attachments by strengthening electrostatic interactions of the tail with the microtubule lattice. Here, we show that removal of the Ndc80 tail, which compromises in vitro microtubule binding, has no effect on kinetochore-microtubule attachments in the Caenorhabditis elegans embryo...
May 22, 2017: Developmental Cell
https://www.readbyqxmd.com/read/28534814/autophagy-regulates-proteasome-inhibitor-induced-pigmentation-in-human-embryonic-stem-cell-derived-retinal-pigment-epithelial-cells
#20
Kati Juuti-Uusitalo, Ali Koskela, Niko Kivinen, Johanna Viiri, Juha M T Hyttinen, Mika Reinisalo, Arto Koistinen, Hannu Uusitalo, Debasish Sinha, Heli Skottman, Kai Kaarniranta
The impairment of autophagic and proteasomal cleansing together with changes in pigmentation has been documented in retinal pigment epithelial (RPE) cell degeneration. However, the function and co-operation of these mechanisms in melanosome-containing RPE cells is still unclear. We show that inhibition of proteasomal degradation with MG-132 or autophagy with bafilomycin A1 increased the accumulation of premelanosomes and autophagic structures in human embryonic stem cell (hESC)-derived RPE cells. Consequently, upregulation of the autophagy marker p62 (also known as sequestosome-1, SQSTM1) was confirmed in Western blot and perinuclear staining...
May 19, 2017: International Journal of Molecular Sciences
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