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Tubulin

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https://www.readbyqxmd.com/read/29348323/epothilone-b-benefits-nigrostriatal-pathway-recovery-by-promoting-microtubule-stabilization-after-intracerebral-hemorrhage
#1
Yang Yang, Xuan Zhang, Hongfei Ge, Wei Liu, Eryi Sun, Yuanyuan Ma, Hengli Zhao, Rongwei Li, Weixiang Chen, Jichao Yuan, Qianwei Chen, Yujie Chen, Xin Liu, John H Zhang, Rong Hu, Xiaotang Fan, Hua Feng
BACKGROUND: Many previous clinical studies have demonstrated that the nigrostriatal pathway, which plays a vital role in movement adjustment, is significantly impaired after stroke, according to medical imaging and autopsies. However, the basic pathomorphological changes have been poorly investigated to date. This study was designed to explore the pathomorphological changes, mechanism, and therapeutic method of nigrostriatal impairment after intracerebral hemorrhage (ICH). METHODS AND RESULTS: Intrastriatal injection of autologous blood or microtubule depolymerization reagent nocodazole was performed to mimic the pathology of ICH in C57/BL6 mice...
January 18, 2018: Journal of the American Heart Association
https://www.readbyqxmd.com/read/29348145/fbxl13-directs-the-proteolysis-of-cep192-to-regulate-centrosome-homeostasis-and-cell-migration
#2
Ella Fung, Carmen Richter, Hong-Bin Yang, Isabell Schäffer, Roman Fischer, Benedikt M Kessler, Florian Bassermann, Vincenzo D'Angiolella
Aberrant centrosome organisation with ensuing alterations of microtubule nucleation capacity enables tumour cells to proliferate and invade despite increased genomic instability. CEP192 is a key factor in the initiation process of centrosome duplication and in the control of centrosome microtubule nucleation. However, regulatory means of CEP192 have remained unknown. Here, we report that FBXL13, a binding determinant of SCF (SKP1-CUL1-F-box)-family E3 ubiquitin ligases, is enriched at centrosomes and interacts with the centrosomal proteins Centrin-2, Centrin-3, CEP152 and CEP192...
January 18, 2018: EMBO Reports
https://www.readbyqxmd.com/read/29344837/evaluation-of-the-profile-and-mechanism-of-neurotoxicity-of-water-soluble-cu-p-4-pf6-and-au-p-4-pf6-p-thp-or-pta-anticancer-complexes
#3
C Ceresa, G Nicolini, S Semperboni, V Gandin, M Monfrini, F Avezza, P Alberti, A Bravin, M Pellei, C Santini, Guido Cavaletti
[Cu(thp)4]PF6, [Cu(PTA)4]PF6, [Au(thp)4]PF6 and [Au(PTA)4]PF6 are phosphane (thp = tris(hydroxymethyl)phosphane; PTA = 1,3,5-triaza-7-phosphaadamantane) copper(I) and gold(I) water-soluble complexes characterized by high anticancer activity in a wide range of solid tumors, often able to overcome drug resistance of platinum-based compounds. For these reasons, they have been proposed as a valid alternative to platinum-based chemotherapeutic drugs (e.g., cisplatin and oxaliplatin). In vitro experiments performed on organotypic cultures of dorsal root ganglia (DRG) from 15-day-old rat embryos revealed that copper-based compounds were not neurotoxic even at concentrations higher than the IC50 obtained in human cancer cells while [Au(PTA)4]PF6 was neurotoxic at lower concentration than IC50 in cancer cell lines...
January 17, 2018: Neurotoxicity Research
https://www.readbyqxmd.com/read/29342911/effects-of-acanthopanax-senticosus-on-brain-injury-induced-by-simulated-spatial-radiation-in-mouse-model-based-on-pharmacokinetics-and-comparative-proteomics
#4
Yingyu Zhou, Cuilin Cheng, Denis Baranenko, Jiaping Wang, Yongzhi Li, Weihong Lu
The active compounds in Acanthopanax senticosus (AS) have different pharmacokinetic characteristics in mouse models. Cmax and AUC of Acanthopanax senticosus polysaccharides (ASPS) were significantly reduced in radiation-injured mice, suggesting that the blood flow of mouse was blocked or slowed, due to the pathological state of ischemia and hypoxia, which are caused by radiation. In contrast, the ability of various metabolizing enzymes to inactivate, capacity of biofilm transport decrease, and lessening of renal blood flow accounts for radiation, resulting in the accumulation of syringin and eleutheroside E in the irradiated mouse...
January 15, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29341414/post-translational-incorporation-of-3-4-dihydroxyphenylalanine-into-the-c-terminus-of-%C3%AE-tubulin-in-living-cells
#5
Yanela M Dentesano, Yanina Ditamo, Cristian Hansen, Carlos A Arce, C Gastón Bisig
The C-terminal tyrosine (Tyr) of the α-tubulin chain is subjected to post-translational removal and re-addition in a process termed the "detyrosination/tyrosination cycle". We showed in previous studies using soluble rat brain extracts that L-3,4-dihydroxyphenylalanine (L-Dopa) is incorporated into the same site as Tyr. We now demonstrate that L-Dopa incorporation into tubulin also occurs in living cells. We detected such incorporation by determining the "tyrosination state" of tubulin before and after incubation of cells in the presence of L-Dopa...
January 17, 2018: FEBS Journal
https://www.readbyqxmd.com/read/29341179/better-characterization-of-vinflunine-pharmacokinetics-variability-and-exposure-toxicity-relationship-to-improve-its-use-analyses-from-18-trials
#6
A Schmitt, L Nguyen, G Zorza, P Ferré, A Pétain
AIMS: Vinflunine is a novel tubulin-targeted inhibitor indicated as a single agent for the treatment of bladder cancers after failure of prior platinum-based therapy. Its pharmacokinetics (PK) and pharmacodynamics (PD) have been independently characterized through several phase I and phase II studies. However, no global pharmacometric analysis had been conducted yet. METHODS: Vinflunine concentrations and safety data from 18 phase I and phase II studies were used to conduct population PK and PK/PD analysis, using Nonmem...
January 17, 2018: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29340076/mitochondrial-ros-activates-erk-autophagy-pathway-as-a-protected-mechanism-against-deoxypodophyllotoxin-induced-apoptosis
#7
Sang-Hun Kim, Kwang-Youn Kim, Sul-Gi Park, Sun-Nyoung Yu, Young-Wook Kim, Hyo-Won Nam, Hyun-Hee An, Young-Woo Kim, Soon-Cheol Ahn
Deoxypodophyllotoxin (DPT) is a naturally occurring flavolignan isolated from Anthriscus sylvestris. Recently, it has been reported that DPT inhibits tubulin polymerization and induces G2/M cell cycle arrest followed by apoptosis through multiple cellular processes. Despite these findings, details regarding the cellular and molecular mechanisms underlying the DPT-mediated cell death have been poorly understood. To define a mechanism of DPT-mediated cell death response, we examined whether DPT activates signaling pathways for autophagy and apoptosis...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29340075/extracting-microtentacle-dynamics-of-tumor-cells-in-a-non-adherent-environment
#8
Eleanor C Ory, Desu Chen, Kristi R Chakrabarti, Peipei Zhang, James I Andorko, Christopher M Jewell, Wolfgang Losert, Stuart S Martin
During metastasis, tumor cells dynamically change their cytoskeleton to traverse through a variety of non-adherent microenvironments, including the vasculature or lymphatics. Due to the challenges of imaging drift in non-adhered tumor cells, the dynamic cytoskeletal phenotypes are poorly understood. We present a new approach to analyze the dynamic cytoskeletal phenotypes of non-adhered cells that support microtentacles (McTNs), which are cell surface projections implicated in metastatic reattachment. Combining a recently-developed cell tethering method with a novel image analysis framework allowed McTN attribute extraction...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29340049/pharmacological-treatment-with-inhibitors-of-nuclear-export-enhances-the-antitumor-activity-of-docetaxel-in-human-prostate-cancer
#9
Giovanni Luca Gravina, Andrea Mancini, Alessandro Colapietro, Francesco Marampon, Roberta Sferra, Simona Pompili, Leda Assunta Biordi, Roberto Iorio, Vincenzo Flati, Christian Argueta, Yosef Landesman, Michael Kauffman, Sharon Shacham, Claudio Festuccia
Background and aims: Docetaxel (DTX) modestly increases patient survival of metastatic castration-resistant prostate cancer (mCRPC) due to insurgence of pharmacological resistance. Deregulation of Chromosome Region Maintenance (CRM-1)/ exportin-1 (XPO-1)-mediated nuclear export may play a crucial role in this phenomenon. Material and methods: Here, we evaluated the effects of two Selective Inhibitor of Nuclear Export (SINE) compounds, selinexor (KPT-330) and KPT-251, in association with DTX by using 22rv1, PC3 and DU145 cell lines with their...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29340040/identifying-the-dynamics-of-actin-and-tubulin-polymerization-in-ipscs-and-in-ipsc-derived-neurons
#10
Valentina Magliocca, Stefania Petrini, Tiziana Franchin, Rossella Borghi, Alessia Niceforo, Zeinab Abbaszadeh, Enrico Bertini, Claudia Compagnucci
The development of the nervous system requires cytoskeleton-mediated processes coordinating self-renewal, migration, and differentiation of neurons. It is not surprising that many neurodevelopmental problems and neurodegenerative disorders are caused by deficiencies in cytoskeleton-related genes. For this reason, we focus on the cytoskeletal dynamics in proliferating iPSCs and in iPSC-derived neurons to better characterize the underpinnings of cytoskeletal organization looking at actin and tubulin repolymerization studies using the cell permeable probes SiR-Actin and SiR-Tubulin...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29340014/cymbopogon-citratus-and-camellia-sinensis-extracts-selectively-induce-apoptosis-in-cancer-cells-and-reduce-growth-of-lymphoma-xenografts-in-vivo
#11
Cory Philion, Dennis Ma, Ivan Ruvinov, Fadi Mansour, Christopher Pignanelli, Megan Noel, Ammar Saleem, John Arnason, Mark Rodrigues, Inderpal Singh, Jesse Ropat, Siyaram Pandey
Cancer cells are reported to have elevated levels of reactive oxygen species (ROS) and are highly dependent on cellular defense mechanisms against oxidative stress. Numerous nutraceuticals and natural polyphenolic compounds have a wide range of abilities to alter cellular redox states with potential implications in various diseases. Furthermore, therapeutic options for cancers are mostly nonselective treatments including genotoxic or tubulin-targeting compounds. Some of the natural extracts, containing multiple bioactive compounds, could target multiple pathways in cancer cells to selectively induce cell death...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29339327/the-chaperonin-cct-promotes-the-formation-of-fibrillar-aggregates-of-%C3%AE-tubulin
#12
Luis Pouchucq, Pablo Lobos-Ruiz, Gisela Araya, José María Valpuesta, Octavio Monasterio
The type II chaperonin CCT is involved in the prevention of the pathogenesis of numerous human misfolding disorders, as it sequesters misfolded proteins, blocks their aggregation and helps them to achieve their native state. In addition, it has been reported that CCT can prevent the toxicity of non-client amyloidogenic proteins by the induction of non-toxic aggregates, leading to new insight in chaperonin function as an aggregate remodeling factor. Here we add experimental evidence to this alternative mechanism by which CCT actively promotes the formation of conformationally different aggregates of γ-tubulin, a non-amyloidogenic CCT client protein, which are mediated by specific CCT-γ-tubulin interactions...
January 12, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29339176/the-absence-of-class-iii-%C3%AE-tubulin-is-predictive-of-a-favorable-response-to-nab-paclitaxel-and-gemcitabine-in-patients-with-unresectable-pancreatic-ductal-adenocarcinoma
#13
Akihisa Kato, Aya Naiki-Ito, Itaru Naitoh, Kazuki Hayashi, Takahiro Nakazawa, Shuya Shimizu, Yuji Nishi, Fumihiro Okumura, Inoue Tadahisa, Hiroki Takada, Hiromu Kondo, Michihiro Yoshida, Satoru Takahashi, Takashi Joh
The combined administration of nab-paclitaxel and gemcitabine (nab-P + Gem) is a standard chemotherapy for unresectable pancreatic ductal adenocarcinoma (UR-PDAC); thus, a predictive biomarker to identify patients best suited for nab-P + Gem therapy would be useful. Class III β-tubulin (TUBB3) has been reported to be a predictive marker for taxane resistance in various tumors. However, the correlation between TUBB3 expression and the response to nab-P + Gem in patients with UR-PDAC has not been evaluated. We retrospectively reviewed 75 patients with UR-PDAC who received nab-P + Gem...
January 12, 2018: Human Pathology
https://www.readbyqxmd.com/read/29339086/the-il-6-stat3-pathway-regulates-adhesion-molecules-and-cytoskeleton-of-endothelial-cells-in-thromboangiitis-obliterans
#14
Zheng Wei, Wenjing Jiang, Hengzhen Wang, Hali Li, Bo Tang, Bing Liu, Hongchi Jiang, Xueying Sun
Thromboangiitis obliterans (TAO) (also known as Buerger's disease) is an inflammatory vascular disease that predominantly affects small- and medium-sized blood vessels of extremities. Endothelial cells play critical roles in the initiation and progression of this disease, but the underlying mechanisms remain unclear. In the present study, we demonstrate that patients with TAO had significantly higher levels of interleukin-6 (IL-6), soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1) in their plasmas, and the involved arterial tissues expressed higher levels of phosphorylated signal transducer and activator of transcription 3 (p-STAT3), ICAM-1 and VCAM-1...
January 12, 2018: Cellular Signalling
https://www.readbyqxmd.com/read/29338542/the-novel-microtubule-associated-cap-glycine-protein-cgp1-governs-growth-differentiation-and-virulence-of-cryptococcus-neoformans
#15
Li Li Wang, Kyung-Tae Lee, Kwang-Woo Jung, Dong-Gi Lee, Yong-Sun Bahn
Microtubules are involved in mechanical support, cytoplasmic organization, and several cellular processes by interacting with diverse microtubule-associated proteins such as plus-end tracking proteins, motor proteins, and tubulin-folding cofactors. A number of the cytoskeleton-associated proteins (CAPs) contain the CAP-glycine-rich (CAP-Gly) domain, which is evolutionarily conserved and generally considered to bind to α-tubulin to regulate the function of microtubules. However, there has been a dearth of research on CAP-Gly proteins in fungal pathogens, including Cryptococcus neoformans, which is a global cause of fatal meningoencephalitis in immunocompromised patients...
January 17, 2018: Virulence
https://www.readbyqxmd.com/read/29338033/intermittent-low-dose-carbon-monoxide-exposure-enhances-survival-and-dopaminergic-differentiation-of-human-neural-stem-cells
#16
Nanna Dreyer-Andersen, Ana Sofia Almeida, Pia Jensen, Morad Kamand, Justyna Okarmus, Tine Rosenberg, Stig Düring Friis, Alberto Martínez Serrano, Morten Blaabjerg, Bjarne Winther Kristensen, Troels Skrydstrup, Jan Bert Gramsbergen, Helena L A Vieira, Morten Meyer
Exploratory studies using human fetal tissue have suggested that intrastriatal transplantation of dopaminergic neurons may become a future treatment for patients with Parkinson's disease. However, the use of human fetal tissue is compromised by ethical, regulatory and practical concerns. Human stem cells constitute an alternative source of cells for transplantation in Parkinson's disease, but efficient protocols for controlled dopaminergic differentiation need to be developed. Short-term, low-level carbon monoxide (CO) exposure has been shown to affect signaling in several tissues, resulting in both protection and generation of reactive oxygen species...
2018: PloS One
https://www.readbyqxmd.com/read/29337054/deficiency-of-primary-cilia-in-kidney-epithelial-cells-induces-epithelial-to-mesenchymal-transition
#17
Sang Jun Han, Jin Ki Jung, Seung-Soon Im, Seong-Ryong Lee, Byeong-Churl Jang, Kwon Moo Park, Jee In Kim
Primary cilium is a microtubule-based non-motile organelle that plays critical roles in kidney pathophysiology. Our previous studies revealed that the lengths of primary cilia decreased upon renal ischemia/reperfusion injury and oxidative stress, and restored with recovery. Here, we tested the hypothesis that lack of primary cilium causes epithelial to mesenchymal transition (EMT) of kidney tubule cells. We investigated the alteration of length of primary cilia in TGF-β-induced EMT via visualization of primary cilia by fluorescence staining against acetylated α-tubulin...
January 11, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29336686/phylogeny-and-taxonomy-of-favolus-basidiomycota
#18
Jun-Liang Zhou, Bao-Kai Cui
Favolus is a natural genus that is closely related to Polyporus. A taxonomic study of Favolus was carried out based on morphological characteristics and phylogenetic analysis of the internal transcribed spacer (ITS) region (ITS1-5.8S-ITS2 = ITS) and 18S and 28S genes of the nuc rDNA, translation elongation factor 1-α gene (TEF1-α), the mt 16S rDNA gene (mt rrnS), β-tubulin gene (TBB1), and the RNA polymerase II largest subunit (RPB1) and second largest subunit (RPB2) genes. Fourteen specimens collected from subtropical to tropical regions in China were shown to be different from existing Favolus species...
November 30, 2017: Mycologia
https://www.readbyqxmd.com/read/29336252/colchicine-in-gout-an-update
#19
Tristan Pascart, Pascal Richette
Despite the fact that colchicine is by far the most ancient treatment for gout, new data are still being gathered. In gout, colchicine's ability to block polymerization of tubulin prevents the activation of the inflammasome. Efficacy of colchicine for the treatment of gout flares has been demonstrated only recently by a randomized-controlled trial, but it still has not been compared to other drugs. Use of colchicine is impaired by the impact of underlying comorbid conditions and drug interactions that can considerably modify its pharmacokinetics and pharmacodynamics...
January 14, 2018: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/29334652/insight-into-the-expression-variation-of-metal-responsive-genes-in-the-seedling-of-date-palm-phoenix-dactylifera
#20
Zayneb Chaâbene, Agnieszka Rorat, Imen Rekik Hakim, Fabien Bernard, Grubb C Douglas, Amine Elleuch, Franck Vandenbulcke, Hafedh Mejdoub
Phytochelatin synthase and metallothionein gene expressions were monitored via qPCR in order to investigate the molecular mechanisms involved in Cd and Cr detoxification in date palm (Phoenix dactylifera). A specific reference gene validation procedure using BestKeeper, NormFinder and geNorm programs allowed selection of the three most stable reference genes in a context of Cd or Cr contamination among six reference gene candidates, namely elongation factor α1, actin, aldehyde dehydrogenase, SAND family, tubulin 6 and TaTa box binding protein...
December 28, 2017: Chemosphere
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