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Dynasore

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https://www.readbyqxmd.com/read/28327657/dynasore-impairs-vegfr2-signalling-in-an-endocytosis-independent-manner
#1
Dimitris Basagiannis, Sofia Zografou, Katerina Galanopoulou, Savvas Christoforidis
VEGFR2 is a critical angiogenic receptor playing a key role in vascular homeostasis. Upon activation by VEGF, VEGFR2 becomes endocytosed. Internalisation of VEGFR2 is facilitated, in part, through clathrin mediated endocytosis (CME), the role of which in VEGFR2 function is debated. Here, we confirm the contribution of CME in VEGFR2 uptake. However, curiously, we find that different approaches of inhibition of CME exert contradictory effects on VEGF signalling; knockdown of clathrin, or of dynamin, or overexpression of dynamin K44A, do not affect VEGF-induced phosphorylation of ERK1/2, while dynasore causes strong inhibition...
March 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28323206/ligands-of-peroxisome-proliferator-activated-receptor-alpha-promote-glutamate-transporter-1-endocytosis-in-astrocytes
#2
Hui-Ting Huang, Chih-Kai Liao, Wen-Tai Chiu, Shun-Fen Tzeng
Astrocytes, a stellate-shape glial population in the central nervous system (CNS), maintain glutamate homeostasis in adult CNS by undergoing glutamate uptake at the synapse through their glutamate transporter-1 (GLT-1). Peroxisome proliferator-activated receptor-α (PPARα) can be activated by endogenous saturated fatty acids to regulate astrocytic lipid metabolism and functions. However, it is unclear if PPARα can exert the regulatory action on GLT-1 expression in astrocytes. This study showed that treatment with palmitic acid (PA) and the other two PPARα agonists (GW 7647 and WY 14,643) caused no change in the morphology of astrocytes, whereas membranous GLT-1 protein levels in astrocytes were significantly decreased by PA and PPARα agonists...
March 16, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/28296078/botulinum-neurotoxin-type-b-uses-a-distinct-entry-pathway-mediated-by-cdc42-into-intestinal-cells-versus-neuronal-cells
#3
Chloé Connan, Marie Voillequin, Carolina Varela Chavez, Christelle Mazuet, Christian Leveque, Sandrine Vitry, Alain Vandewalle, Michel R Popoff
Botulinum neurotoxins (BoNTs) are responsible for severe flaccid paralysis by inhibiting the release of acetylcholine at the neuromuscular junctions. BoNT/B most often induces mild forms of botulism with predominant dysautonomic symptoms. In food borne botulism and botulism by intestinal colonization such as infant botulism, which are the most frequent naturally acquired forms of botulism, the digestive tract is the main entry route of BoNTs into the organism. We previously showed that BoNT/B translocates through mouse intestinal barrier by an endocytosis-dependent mechanism and subsequently targets neuronal cells, mainly cholinergic neurons, in the intestinal mucosa and musculosa...
March 11, 2017: Cellular Microbiology
https://www.readbyqxmd.com/read/28188849/endocytosis-contributes-to-bmp2-induced-smad-signalling-and-neuronal-growth
#4
Shane V Hegarty, Aideen M Sullivan, Gerard W O'Keeffe
Bone morphogenetic protein 2 (BMP2) is a neurotrophic factor which induces the growth of midbrain dopaminergic (DA) neurons in vitro and in vivo, and its neurotrophic effects have been shown to be dependent on activation of BMP receptors (BMPRs) and Smad 1/5/8 signalling. However, the precise intracellular cascades that regulate BMP2-BMPR-Smad-signalling-induced neurite growth remain unknown. Endocytosis has been shown to regulate Smad 1/5/8 signalling and differentiation induced by BMPs. However, these studies were carried out in non-neural cells...
March 16, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28179028/betanodavirus-like-particles-enter-host-cells-via-clathrin-mediated-endocytosis-in-a-cholesterol-ph-and-cytoskeleton-dependent-manner
#5
Runqing Huang, Guohua Zhu, Jing Zhang, Yuxiong Lai, Yu Xu, Jianguo He, Junfeng Xie
Betanodavirus, also referred to nervous necrosis virus (NNV), is the causative agent of the fatal disease, viral nervous necrosis and has brought significant economic losses in marine and freshwater cultured fish, especially larvae and juveniles. Here, we used an established invasion model with virus-like particle (VLP)-cells, mimicking orange-spotted grouper nervous necrosis virus (OGNNV), to investigate the crucial events of virus entry. VLP were observed in the perinuclear regions of Asian sea bass (SB) cells within 1...
February 8, 2017: Veterinary Research
https://www.readbyqxmd.com/read/28131869/quantifying-receptor-trafficking-and-colocalization-with-confocal-microscopy
#6
Jeremy A Pike, Iain B Styles, Joshua Z Rappoport, John K Heath
Confocal microscopy is a powerful tool for the study of cellular receptor trafficking and endocytosis. Unbiased and robust image analysis workflows are required for the identification, and study, of aberrant trafficking. After a brief review of related strategies, identifying both good and bad practice, custom workflows for the analysis of live cell 3D time-lapse data are presented. Strategies for data pre-processing, including denoising and background subtraction are considered. We use a 3D level set protocol to accurately segment cells using only the signal from fluorescently labelled receptor...
January 26, 2017: Methods: a Companion to Methods in Enzymology
https://www.readbyqxmd.com/read/28131082/mitochondrial-dynamics-in-type-2-diabetes-pathophysiological-implications
#7
REVIEW
Susana Rovira-Llopis, Celia Bañuls, Noelia Diaz-Morales, Antonio Hernandez-Mijares, Milagros Rocha, Victor M Victor
Mitochondria play a key role in maintaining cellular metabolic homeostasis. These organelles have a high plasticity and are involved in dynamic processes such as mitochondrial fusion and fission, mitophagy and mitochondrial biogenesis. Type 2 diabetes is characterised by mitochondrial dysfunction, high production of reactive oxygen species (ROS) and low levels of ATP. Mitochondrial fusion is modulated by different proteins, including mitofusin-1 (MFN1), mitofusin-2 (MFN2) and optic atrophy (OPA-1), while fission is controlled by mitochondrial fission 1 (FIS1), dynamin-related protein 1 (DRP1) and mitochondrial fission factor (MFF)...
April 2017: Redox Biology
https://www.readbyqxmd.com/read/28059487/%C3%AE-tocopheryl-phosphate-induces-vegf-expression-via-cd36-pi3k%C3%AE-in-thp-1-monocytes
#8
Jean-Marc Zingg, Angelo Azzi, Mohsen Meydani
The CD36 scavenger receptor binds several ligands and mediates ligand uptake and ligand-dependent signal transduction and gene expression, events that may involve CD36 internalization. Here we show that CD36 internalization in THP-1 monocytes is triggered by α-tocopherol (αT) and more strongly by α-tocopheryl phosphate (αTP) and EPC-K1, a phosphate diester of αTP and L-ascorbic acid. αTP-triggered CD36 internalization is prevented by the specific covalent inhibitor of selective lipid transport by CD36, sulfo-N-succinimidyl oleate (SSO)...
January 6, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/27919959/dynamin-2-inhibitors-as-novel-therapeutic-agents-against-cervical-cancer-cells
#9
Yoo-Young Lee, Hye-Kyung Jeon, Jungeun Lee, Ji Eun Hong, In-Gu Do, Chel Hun Choi, Tae-Joong Kim, Byoung-Gie Kim, Duk-Soo Bae, Yong-Chul Kim, Jeong-Won Lee
AIM: We investigated the feasibility of dynamin 2 as a potential treatment target in cervical cancer cells. MATERIALS AND METHODS: We performed tissue microarray for dynamin 2 expression in 208 patients with early cervical cancer and in vitro in HeLa cells with dynamin 2 inhibitors MiTMAB, OcTMAB, Dynasore, and DD-6. RESULTS: Tumor size greater than 2 cm or tumor invasion of more than half of the entire cervix was associated with expression of dynamin 2 compared to no expression (p=0...
2016: Anticancer Research
https://www.readbyqxmd.com/read/27847966/therapeutic-potential-of-pro-angiogenic-bpc157-is-associated-with-vegfr2-activation-and-up-regulation
#10
Ming-Jer Hsieh, Hsien-Ta Liu, Chao-Nin Wang, Hsiu-Yun Huang, Yuling Lin, Yu-Shien Ko, Jong-Shyan Wang, Vincent Hung-Shu Chang, Jong-Hwei S Pang
BPC 157, a pentadecapeptide with extensive healing effects, has recently been suggested to contribute to angiogenesis. However, the underlying mechanism is not yet clear. The present study aimed to explore the potential therapeutic effect and pro-angiogenic mechanism of BPC 157. As demonstrated by the chick chorioallantoic membrane (CAM) assay and endothelial tube formation assay, BPC 157 could increase the vessel density both in vivo and in vitro, respectively. BPC 157 could also accelerate the recovery of blood flow in the ischemic muscle of the rat hind limb as detected by laser Doppler scanning, indicating the promotion of angiogenesis...
November 15, 2016: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/27835898/prognostic-significance-of-usp33-in-advanced-colorectal-cancer-patients-new-insights-into-%C3%AE-arrestin-dependent-erk-signaling
#11
Hongda Liu, Qun Zhang, Kangshuai Li, Zheng Gong, Zhaochen Liu, Yunfei Xu, Mary Hannah Swaney, Kunhong Xiao, Yuxin Chen
Patients with liver metastases of colorectal cancer (CRCLM) have a poorer prognosis compared to colorectal cancer (CRC) patients in local stage. Evaluating the recurrence and overall survival of advanced patients is critical in improving disease treatment and clinical outcome. Here we investigated the expression pattern of USP33, a deubiquitinating enzyme, in both primary CRC tissues and liver metastases tissues. Univariate and multivariate analyses identified that low expression of USP33 in CRCLM tissues indicated high recurrence risk and poor overall prognosis...
November 8, 2016: Oncotarget
https://www.readbyqxmd.com/read/27822712/dynasore-improves-motor-function-recovery-via-inhibition-of-neuronal-apoptosis-and-astrocytic-proliferation-after-spinal-cord-injury-in-rats
#12
Gang Li, Feifei Shen, Zhongkai Fan, Yangsong Wang, Xiangquan Kong, Deshui Yu, Xiaodong Zhi, Gang Lv, Yang Cao
Spinal cord injury (SCI) is a common and devastating central nervous system insult which lacks efficient treatment. Our previous experimental findings indicated that dynamin-related protein 1 (Drp1) mediates mitochondrial fission during SCI, and inhibition of Drp1 plays a significant protective effect after SCI in rats. Dynasore inhibits GTPase activity at both the plasma membrane (dynamin 1, 2) and the mitochondria membrane (Drp1). The aim of the present study was to investigate the beneficial effects of dynasore on SCI and its underlying mechanism in a rat model...
November 7, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27802433/targeting-dynamin-2-as-a-novel-pathway-to-inhibit-cardiomyocyte-apoptosis-following-oxidative-stress
#13
Danchen Gao, Jian Yang, Yutao Wu, Qiwen Wang, Qiaoling Wang, En Yin Lai, Jianhua Zhu
BACKGROUND/AIMS: Inhibition of Drp-1-mediated mitochondrial fission limits reactive oxygen species (ROS) production and apoptosis in cardiomyocytes subjected to ischemia/reperfusion injury. It remains unknown if Dynamin 2 inhibition results in similar protective effects. Here we studied the role of Dynamin 2 in cardiomyocyte oxidative stress-induced apoptosis and ROS production. METHODS: The effect of lentiviral shRNA (lv5-shRNA) mediated Dynamin 2 knockdown on apopotosis, mitochondria, and ROS production were studied in neonatal mouse cardiomycytes, which were further treated with either selective Drp1 inhibitor mdivi-1 or the Dynamin 2/Drp1 inhibitor Dynasore...
2016: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/27779751/distinct-subcellular-mechanisms-for-the-enhancement-of-the-surface-membrane-expression-of-sk2-channel-by-its-interacting-proteins-%C3%AE-actinin2-and-filamin-a
#14
Zheng Zhang, Hannah A Ledford, Seojin Park, Wenying Wang, Sassan Rafizadeh, Hyo Jeong Kim, Wilson Xu, Ling Lu, Victor C Lau, Anne A Knowlton, Xiao-Dong Zhang, Ebenezer N Yamoah, Nipavan Chiamvimonvat
KEY POINTS: Ion channels are transmembrane proteins that are synthesized within the cells but need to be trafficked to the cell membrane for the channels to function. Small-conductance, Ca(2+) -activated K(+) channels (SK, KCa 2) are unique subclasses of K(+) channels that are regulated by Ca(2+) inside the cells; they are expressed in human atrial myocytes and responsible for shaping atrial action potentials. We have previously shown that interacting proteins of SK2 channels are important for channel trafficking to the membrane...
October 25, 2016: Journal of Physiology
https://www.readbyqxmd.com/read/27771248/dynamin2-gtpase-contributes-to-invadopodia-formation-in-invasive-bladder-cancer-cells
#15
Yubai Zhang, Maya Nolan, Hiroshi Yamada, Masami Watanabe, Yasutomo Nasu, Kohji Takei, Tetsuya Takeda
Cancer cell invasion is mediated by actin-based membrane protrusions termed invadopodia. Invadopodia consist of "core" F-actin bundles associated with adhesive and proteolytic machineries promoting cell invasion by degrading extracellular matrix (ECM). Formation of the F-actin core in invadopodia is regulated by various actin-binding proteins including Arp2/3 complex and cortactin. Dynamin GTPase localizes to the invadopodia and is implicated in cancer cell invasion, but its precise role at the invadopodia remained elusive...
October 19, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27748822/reduction-of-dynamin-1-in-the-hippocampus-of-aged-mice-is-associated-with-the-decline-in-hippocampal%C3%A2-dependent-memory
#16
Dae Young Yoo, Hyo Young Jung, Jong Whi Kim, Hee Sun Yim, Dae Won Kim, Hajin Nam, Jun Gyo Suh, Jung Hoon Choi, Moo-Ho Won, Yeo Sung Yoon, In Koo Hwang
Dynamin 1 is a known synaptic protein, which has is key in the presynaptic regulation of endocytosis. The present study investigated the association between age and the observed changes in Morris water maze performance, and immunoreactivity and protein levels of dynamin 1 in the mouse hippocampal formation. In addition, the effects of dynasore, an inhibitor of dynamin 1, on the hippocampal dependent memory were determined to elucidate the correlation between dynamin 1 and memory. In the training phase of the Morris water maze task, the mean escape latency of the aged group (24 months old) was significantly longer, compared with that of the adult group (4 months old), although the average swimming speed and the total distance traveled during the probe trial were similar in the two groups...
November 2016: Molecular Medicine Reports
https://www.readbyqxmd.com/read/27733684/hypotonic-stress-induced-down-regulation-of-claudin-1-and-2-mediated-by-dephosphorylation-and-clathrin-dependent-endocytosis-in-renal-tubular-epithelial-cells
#17
Naoko Fujii, Yukinobu Matsuo, Toshiyuki Matsunaga, Satoshi Endo, Hideki Sakai, Masahiko Yamaguchi, Yasuhiro Yamazaki, Junko Sugatani, Akira Ikari
Hypotonic stress decreased claudin-1 and -2 expression levels in renal tubular epithelial HK-2 and Madin-Darby canine kidney cells. Here, we examined the regulatory mechanism involved in this decrease. The hypotonicity-induced decrease in claudin expression was inhibited by the following: SB202190, a p38 MAPK inhibitor, but not by U0126, a MEK inhibitor; Go6983, a protein kinase C inhibitor; or SP600125, a Jun N-terminal protein kinase inhibitor. Hypotonic stress increased transepithelial electrical resistance, which was inhibited by SB202190...
November 18, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27671041/mitogen-activated-protein-kinases-are-required-for-effective-infection-of-human-choroid-plexus-epithelial-cells-by-listeria-monocytogenes
#18
Stefanie Dinner, Julian Kaltschmidt, Carolin Stump-Guthier, Svetlana Hetjens, Hiroshi Ishikawa, Tobias Tenenbaum, Horst Schroten, Christian Schwerk
Listeria monocytogenes, a Gram-positive bacterium, can cause meningitis after invading the human central nervous system. The blood-cerebrospinal fluid barrier (BCSFB), located at the epithelium of the choroid plexus, is a possible entry site for L. monocytogenes into the brain, and in vitro L. monocytogenes invades human choroid plexus epithelial papilloma (HIBCPP) cells. Although host cell signal transduction subsequent to infection by L. monocytogenes has been investigated, the role of mitogen-activated protein kinases (MAPK) is not clarified yet...
January 2017: Microbes and Infection
https://www.readbyqxmd.com/read/27596061/effects-of-membrane-properties-on-the-binding-activities-of-the-hn-and-hc-heavy-chain-domains-of-botulinum-neurotoxin-a
#19
B Vijayalakshmi Ayyar, M Zouhair Atassi
Binding behaviors of the HN and the HC domains of BoNT/A were investigated individually to identify if there exist any differences in their interaction with the cell membrane. Recombinant fragments corresponding to both BoNT/A HN and HC regions were prepared (HN519-845 and HC967-1296) and their binding to synaptic proteins was verified. The binding behaviors of these heavy-chain domains were analyzed by treating the Neuro 2a, a murine neuroblastoma cell line, with compounds known to alter membrane properties...
December 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27590265/dependence-receptor-involvement-in-subtilisin-induced-long-term-depression-and-in-long-term-potentiation
#20
Trevor W Stone, L Gail Darlington, Caroline M Forrest
The serine protease subtilisin induces a form of long-term depression (LTD) which is accompanied by a reduced expression of the axo-dendritic guidance molecule Unco-ordinated-5C (Unc-5C). One objective of the present work was to determine whether a loss of Unc-5C function contributed to subtilisin-induced LTD by using Unc-5C antibodies in combination with the pore-forming agents Triton X-100 (0.005%) or streptolysin O in rat hippocampal slices. In addition we have assessed the effect of subtilisin on the related dependence receptor Deleted in Colorectal Cancer (DCC) and used antibodies to this protein for functional studies...
November 12, 2016: Neuroscience
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