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https://www.readbyqxmd.com/read/28641287/chrysophanol-suppressed-glutamate-induced-hippocampal-neuronal-cell-death-via-regulation-of-dynamin-related-protein-1-dependent-mitochondrial-fission
#1
Unbin Chae, Ju-Sik Min, Hyun Hee Leem, Hyun-Shik Lee, Hong Jun Lee, Sang-Rae Lee, Dong-Seok Lee
Chrysophanic acid, or chrysophanol, is an anthraquinone found in Rheum palmatum, which was used in the preparation of oriental medicine in ancient China. The hippocampus plays a major role in controlling the activities of the short- and long-term memory. It is one of the major regions affected by excessive cell death in Alzheimer's disease. Therefore, neuronal cell-death modulation in the hippocampus is important for maintaining neuronal function. We investigated chrysophanol's effects on glutamate-induced hippocampal neuronal cell death...
June 23, 2017: Pharmacology
https://www.readbyqxmd.com/read/28634208/ligand-and-voltage-gated-ca-2-channels-differentially-regulate-the-mode-of-vesicular-neuropeptide-release-in-mammalian-sensory-neurons
#2
Yeshi Wang, Qihui Wu, Meiqin Hu, Bin Liu, Zuying Chai, Rong Huang, Yuan Wang, Huadong Xu, Li Zhou, Lianghong Zheng, Changhe Wang, Zhuan Zhou
Neuropeptides released from dorsal root ganglion (DRG) neurons play essential roles in the neurotransmission of sensory inputs, including those underlying nociception and pathological pain. Neuropeptides are released from intracellular vesicles through two modes: a partial release mode called "kiss-and-run" (KAR) and a full release mode called "full fusion-like" (FFL). Using total internal reflection fluorescence (TIRF) microscopy, we traced the release of pH-sensitive green fluorescent protein-tagged neuropeptide Y (pHluorin-NPY) from individual dense-core vesicles in the soma and axon of single DRG neurons after Ca(2+) influx through either voltage-gated Ca(2+) channels (VGCCs) or ligand-gated transient receptor potential vanilloid 1 (TRPV1) channels...
June 20, 2017: Science Signaling
https://www.readbyqxmd.com/read/28634116/succinate-induced-neuronal-mitochondrial-fission-and-hexokinase-ii-malfunction-in-ischemic-stroke-therapeutical-effects-of-kaempferol
#3
Bin Wu, Hong Luo, Xu Zhou, Cai-Yi Cheng, Lin Lin, Bao-Lin Liu, Kang Liu, Ping Li, Hua Yang
Mitochondrial dysfunction is known as one of causative factors in ischemic stroke, leading to neuronal cell death. The present work was undertaken to investigate whether succinate induces neuron apoptosis by regulating mitochondrial morphology and function. In neurons, oxygen-glucose deprivation induced succinate accumulation due to the reversal of succinate dehydrogenase (SDH) activation, leading to mitochondrial fission. Kaempferol inhibited mitochondrial fission and maintained mitochondrial HK-II through activation of Akt, and thereby protected neurons from succinate-mediated ischemi injury...
June 17, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28632757/molecular-mechanism-of-drp1-assembly-studied-in-vitro-by-cryo-electron-microscopy
#4
Kaustuv Basu, Driss Lajoie, Tristan Aumentado-Armstrong, Jin Chen, Roman I Koning, Blaise Bossy, Mihnea Bostina, Attila Sik, Ella Bossy-Wetzel, Isabelle Rouiller
Mitochondria are dynamic organelles that continually adapt their morphology by fusion and fission events. An imbalance between fusion and fission has been linked to major neurodegenerative diseases, including Huntington's, Alzheimer's, and Parkinson's diseases. A member of the Dynamin superfamily, dynamin-related protein 1 (DRP1), a dynamin-related GTPase, is required for mitochondrial membrane fission. Self-assembly of DRP1 into oligomers in a GTP-dependent manner likely drives the division process. We show here that DRP1 self-assembles in two ways: i) in the presence of the non-hydrolysable GTP analog GMP-PNP into spiral-like structures of ~36 nm diameter; and ii) in the presence of GTP into rings composed of 13-18 monomers...
2017: PloS One
https://www.readbyqxmd.com/read/28630256/the-small-gtpase-rac1-contributes-to-extinction-of-aversive-memories-of-drug-withdrawal-by-facilitating-gabaa-receptor-endocytosis-in-the-vmpfc
#5
Wei-Sheng Wang, Yun-Yue Ju, Qi-Xin Zhou, Jian-Xin Tang, Meng Li, Lei Zhang, Shuo Kang, Zhong-Guo Chen, Yu-Jun Wang, Hui Ji, Yu-Qiang Ding, Lin Xu, Jing-Gen Liu
Extinction of aversive memories has been a major concern in neuropsychiatric disorders such as anxiety disorders and drug addiction. However, the mechanisms underlying extinction of aversive memories are not fully understood. Here, we report that extinction of conditioned place aversion (CPA) to naloxone-precipitated opiate withdrawal in male rats activates Rho GTPase Rac1 in the ventromedial prefrontal cortex (vmPFC) in a BDNF-dependent manner, which determines GABAA receptor (GABAAR) endocytosis via triggering synaptic translocation of activity-regulated cytoskeleton-associated protein (Arc) through facilitating actin polymerization...
June 19, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28630156/apoptotic-foci-at-mitochondria-in-and-around-bax-pores
#6
REVIEW
Begoña Ugarte-Uribe, Ana J García-Sáez
The permeabilization of the mitochondrial outer membrane by Bax and Bak during apoptosis is considered a key step and a point of no return in the signalling pathway. It is always closely related to the reorganization of mitochondrial cristae that frees cytochrome c to the intermembrane space and to massive mitochondrial fragmentation mediated by the dynamin-like protein Drp1. Despite multiple evidence in favour of a functional link between these processes, the molecular mechanisms that connect them and their relevance for efficient apoptosis signalling remain obscure...
August 5, 2017: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/28627515/lipid-mediated-px-bar-domain-recruitment-couples-local-membrane-constriction-to-endocytic-vesicle-fission
#7
Johannes Schöneberg, Martin Lehmann, Alexander Ullrich, York Posor, Wen-Ting Lo, Gregor Lichtner, Jan Schmoranzer, Volker Haucke, Frank Noé
Clathrin-mediated endocytosis (CME) involves membrane-associated scaffolds of the bin-amphiphysin-rvs (BAR) domain protein family as well as the GTPase dynamin, and is accompanied and perhaps triggered by changes in local lipid composition. How protein recruitment, scaffold assembly and membrane deformation is spatiotemporally controlled and coupled to fission is poorly understood. We show by computational modelling and super-resolution imaging that phosphatidylinositol 3,4-bisphosphate [PI(3,4)P2] synthesis within the clathrin-coated area of endocytic intermediates triggers selective recruitment of the PX-BAR domain protein SNX9, as a result of complex interactions of endocytic proteins competing for phospholipids...
June 19, 2017: Nature Communications
https://www.readbyqxmd.com/read/28623750/lcz696-improves-cardiac-function-via-alleviating-drp1-mediated-mitochondrial-dysfunction-in-mice-with-doxorubicin-induced-dilated-cardiomyopathy
#8
Yan Xia, Zhangwei Chen, Ao Chen, Mingqiang Fu, Zhen Dong, Kai Hu, Xiangdong Yang, Yunzeng Zou, Aijun Sun, Juying Qian, Junbo Ge
AIMS: LCZ696, a novel angiotensin receptor neprilysin inhibitor, is effective in treating heart failure patients. Doxorubicin (DOX) is an effective antitumor medication but the cardiotoxicity limited its clinical use. In this study, we aimed to determine the effect of LCZ696 on DOX-induced cardiomyopathy in mice and in vitro and to explore related mechanisms focusing on fission protein dynamin-related protein 1 (Drp1). METHODS AND RESULTS: In human study, we found that myocardial fission protein Drp1 expression and its ser 616 phosphorylation were significantly increased in dilated cardiomyopathy (DCM) patients...
June 14, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28621662/chronic-lithium-treatment-elicits-its-antimanic-effects-via-bdnf-trkb-dependent-synaptic-downscaling
#9
Erinn S Gideons, Pei-Yi Lin, Melissa Mahgoub, Ege T Kavalali, Lisa M Monteggia
Lithium is widely used as a treatment for Bipolar Disorder although the molecular mechanisms that underlie its therapeutic effects are under debate. In this study, we show brain-derived neurotrophic factor (BDNF) is required for the antimanic-like effects of lithium but not the antidepressant-like effects in mice. We performed whole cell patch clamp recordings of hippocampal neurons to determine the impact of lithium on synaptic transmission that may underlie the behavioral effects. Lithium produced a significant decrease in α-amino-3-hydroxyl-5-methyl-4-isoxazolepropionic acid receptor (AMPAR)-mediated miniature excitatory postsynaptic current (mEPSC) amplitudes due to postsynaptic homeostatic plasticity that was dependent on BDNF and its receptor tropomyosin receptor kinase B (TrkB)...
June 16, 2017: ELife
https://www.readbyqxmd.com/read/28618099/epec-effector-espf-promotes-crumbs3-endocytosis-and-disrupts-epithelial-cell-polarity
#10
Rocio Tapia, Sarah E Kralicek, Gail A Hecht
Enteropathogenic Escherichia coli (EPEC) uses a type three secretion system to inject effector proteins into host intestinal epithelial cells causing diarrhea. EPEC infection redistributes basolateral proteins β1-integrin and Na(+) /K(+) ATPase to the apical membrane of host cells. The Crumbs (Crb) polarity complex (Crb3/Pals1/Patj) is essential for epithelial cell polarization and tight junction (TJ) assembly. Here we demonstrate that EPEC displaces Crb3 and Pals1 from the apical membrane to the cytoplasm of cultured intestinal epithelial cells and colonocytes of infected mice...
June 15, 2017: Cellular Microbiology
https://www.readbyqxmd.com/read/28611181/ligand-activated-notch-undergoes-dtx4-mediated-ubiquitylation-and-bilateral-endocytosis-before-adam10-processing
#11
Patricia Chastagner, Eric Rubinstein, Christel Brou
The Notch signaling pathway, which is activated by cell-cell contact, is a major regulator of cell fate decisions. Mammalian Notch1 is present at the cell surface as a heterodimer of the Notch extracellular domain associated with the transmembrane and intracellular domains. After ligand binding, Notch undergoes proteolysis, releasing the Notch intracellular domain (NICD) that regulates gene expression. We monitored the early steps of activation with biochemical analysis, immunofluorescence analysis, and live-cell imaging of Notch1-expressing cells...
June 13, 2017: Science Signaling
https://www.readbyqxmd.com/read/28607103/dynamin-related-protein-1-inhibition-attenuates-cardiovascular-calcification-in-the-presence-of-oxidative-stress
#12
Maximillian Rogers, Natalia Maldonado-Martinez, Joshua D Hutcheson, Claudia Goettsch, Shinji Goto, Iwao Yamada, Tyler Faits, Hiromi Sesaki, Masanori Aikawa, Elena Aikawa
Rationale: Mitochondrial changes occur during cell differentiation and cardiovascular disease. Dynamin-related protein 1 (DRP1) is a key regulator of mitochondrial fission. We hypothesized that DRP1 plays a role in cardiovascular calcification, a process involving cell differentiation and a major clinical problem with high unmet needs. Objective: To examine the effects of osteogenic promoting conditions on DRP1, and whether DRP1 inhibition alters the development of cardiovascular calcification. Methods and Results: DRP1 was enriched in calcified regions of human carotid arteries, examined by immunohistochemistry...
June 12, 2017: Circulation Research
https://www.readbyqxmd.com/read/28607034/tctex-1-controls-ciliary-resorption-by-regulating-branched-actin-polymerization-and-endocytosis
#13
Masaki Saito, Wataru Otsu, Kuo-Shun Hsu, Jen-Zen Chuang, Teruyuki Yanagisawa, Vincent Shieh, Taku Kaitsuka, Fan-Yan Wei, Kazuhito Tomizawa, Ching-Hwa Sung
The primary cilium is a plasma membrane-protruding sensory organelle that undergoes regulated assembly and resorption. While the assembly process has been studied extensively, the cellular machinery that governs ciliary resorption is less well understood. Previous studies showed that the ciliary pocket membrane is an actin-rich, endocytosis-active periciliary subdomain. Furthermore, Tctex-1, originally identified as a cytoplasmic dynein light chain, has a dynein-independent role in ciliary resorption upon phosphorylation at Thr94...
June 12, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28599479/dynamin-3-suppresses-growth-and-induces-apoptosis-of-hepatocellular-carcinoma-cells-by-activating-inducible-nitric-oxide-synthase-production
#14
Chao Gu, Junliang Yao, Peilong Sun
Dynamin 3 (DNM3) is candidate tumor suppressor against hepatocellular carcinoma (HCC). Downregulation of DNM3 is more frequently identified in HCC tissues than in normal liver tissues. However, the mechanism underlying DNM3-mediated inhibition of HCC remains unclear. The present study demonstrated that DNM3 expression was decreased in human HCC tissues and cell lines. The downregulation of DNM3 promoted cell proliferation by increasing cell cycle-associated proteins, including cyclin D1, cyclin-dependent kinase (CDK) 2 and CDK4...
June 2017: Oncology Letters
https://www.readbyqxmd.com/read/28598422/constriction-of-the-mitochondrial-inner-compartment-is-a-priming-event-for-mitochondrial-division
#15
Bongki Cho, Hyo Min Cho, Youhwa Jo, Hee Dae Kim, Myungjae Song, Cheil Moon, Hyongbum Kim, Kyungjin Kim, Hiromi Sesaki, Im Joo Rhyu, Hyun Kim, Woong Sun
Mitochondrial division is critical for the maintenance and regulation of mitochondrial function, quality and distribution. This process is controlled by cytosolic actin-based constriction machinery and dynamin-related protein 1 (Drp1) on mitochondrial outer membrane (OMM). Although mitochondrial physiology, including oxidative phosphorylation, is also important for efficient mitochondrial division, morphological alterations of the mitochondrial inner-membrane (IMM) have not been clearly elucidated. Here we report spontaneous and repetitive constriction of mitochondrial inner compartment (CoMIC) associated with subsequent division in neurons...
June 9, 2017: Nature Communications
https://www.readbyqxmd.com/read/28596814/enhancement-of-mitochondrial-transfer-by-antioxidants-in-human-mesenchymal-stem-cells
#16
Chia-Jung Li, Po-Kong Chen, Li-Yi Sun, Cheng-Yoong Pang
Excessive reactive oxygen species is the major component of a harsh microenvironment after ischemia/reperfusion injury in human tissues. Combined treatment of N-acetyl-L-cysteine (NAC) and L-ascorbic acid 2-phosphate (AAP) promoted the growth of human mesenchymal stem cells (hMSCs) and suppressed oxidative stress-induced cell death by enhancing mitochondrial integrity and function in vitro. In this study, we aimed to determine whether NAC and AAP (termed MCA) could enhance the therapeutic potential of hMSCs...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28596240/control-of-mitochondrial-homeostasis-by-endocytic-regulatory-proteins
#17
Trey Farmer, James B Reinecke, Shuwei Xie, Kriti Bahl, Naava Naslavsky, Steve Caplan
Mitochondria play essential roles in cellular energy processes, including ATP production, control of ROS, and apoptosis. While mitochondrial function is regulated by the dynamics of fusion and fission, mitochondrial homeostasis remains incompletely understood. Recent studies implicate Dynamin-2 and dynamin-related protein-1 (Drp1), as GTPases involved in mitochondrial fission. We identify the ATPase and endocytic protein, EHD1, as a novel regulator of mitochondrial fission. EHD1-depletion induces a static and elongated network of mitochondria in the cell...
June 8, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28592413/recruitment-of-endosomal-signaling-mediates-the-forskolin-modulation-of-guinea-pig-cardiac-neuron-excitability
#18
Jean C Hardwick, Todd A Clason, John D Tompkins, Beatrice M Girard, Caitlin N Baran, Laura A Merriam, Victor May, Rodney L Parsons
Forskolin, a selective activator of adenylyl cyclase (AC), commonly is used to establish actions of G protein coupled receptors (GPCRs) that are initiated primarily through activation of AC/cAMP signaling pathways. In the present study, forskolin was used to evaluate the potential role of AC/cAMP, which is a major signaling mechanism for the pituitary adenylate cyclase-activating polypeptide (PACAP)-selective PAC1 receptor, in the regulation of guinea pig cardiac neuronal excitability. Forskolin (5-10 µM) increases excitability in ~60 % of the cardiac neurons...
June 7, 2017: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/28590414/mtdna-as-a-mediator-for-expression-of-hypoxia-inducible-factor-1%C3%AE-and-ros-in-hypoxic-neuroblastoma-cells
#19
Chung-Wen Kuo, Meng-Han Tsai, Tsu-Kung Lin, Mao-Meng Tiao, Pei-Wen Wang, Jiin-Haur Chuang, Shang-Der Chen, Chia-Wei Liou
Mitochondria consume O₂ to produce ATP and are critical for adaption of hypoxia, but the role of mitochondria in HIF-1α pathway is as yet unclear. In this study, mitochondrial DNA (mtDNA) enriched (SK-N-AS) and depleted (ρ⁰) cells of neuroblastoma were cultured in a hypoxic chamber to simulate a hypoxic condition and then the major components involved in mitochondrial related pathways, hypoxia-inducible factor 1α (HIF-1α) and reactive oxygen species (ROS) were measured. The results showed that hypoxia-stimulated exposure elevated expression of HIF-1α, which was additionally influenced by level of generated ROS within the cytosol...
June 7, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28584166/sh3p2-plays-a-crucial-role-at-the-step-of-membrane-tubulation-during-cell-plate-formation-in-plants
#20
Gyeongik Ahn, Hyeran Kim, Dae Heon Kim, Nguyen Hong Hanh, Youngdae Yoon, Indira Singaram, Kaveesha J Wijesinghe, Kristen A Johnson, Xiao-Hong Zhuang, Zizhen Liang, Robert V Stahelin, Liwen Jiang, Wonhwa Cho, Byung-Ho Kang, Inhwan Hwang
During cytokinesis in plants, trans-Golgi network-derived vesicles accumulate at the center of dividing cells and undergo various structural changes to give rise to the planar cell plate. However, how this conversion occurs at the molecular level remains elusive. In this study, we report that SH3 domain-containing protein 2 (SH3P2) in Arabidopsis thaliana plays a crucial role in converting vesicles to the planar cell plate. SH3P2 RNAi plants showed cytokinesis-defective phenotypes and produced aggregations of vesicles at the leading edge of the cell plate...
June 5, 2017: Plant Cell
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