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https://www.readbyqxmd.com/read/29351829/inhibition-of-dynamin-related-protein-1-has-neuroprotective-effect-comparable-with-therapeutic-hypothermia-in-a-rat-model-of-cardiac-arrest
#1
Peng Wang, Yi Li, Zhengfei Yang, Tao Yu, Guanghui Zheng, Xiangshao Fang, Zitong Huang, Longyuan Jiang, Wanchun Tang
Dynamin-related protein 1 (Drp1) regulates mitochondrial fission, it has been proven that inhibition of Drp1 by mdivi-1 improves survival and attenuates cerebral ischemic injury after cardiac arrest. In this study, we compared the effects of Drp1 inhibition with therapeutic hypothermia on post-resuscitation neurologic injury in a rat model of cardiac arrest. Rats were randomized into 4 groups: Mdivi-1 treatment group (n = 39), hypothermic group (n = 38), normothermic group (n = 41), and sham group (n = 12)...
January 8, 2018: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/29344294/cardiomyocyte-restricted-low-density-lipoprotein-receptor-related-protein-6-lrp6-deletion-leads-to-lethal-dilated-cardiomyopathy-partly-through-drp1-signaling
#2
Zhidan Chen, Yang Li, Ying Wang, Juying Qian, Hong Ma, Xiang Wang, Guoliang Jiang, Ming Liu, Yanpeng An, Leilei Ma, Le Kang, Jianguo Jia, Chunjie Yang, Guoping Zhang, Ying Chen, Wei Gao, Mingqiang Fu, Zheyong Huang, Huiru Tang, Yichun Zhu, Junbo Ge, Hui Gong, Yunzeng Zou
Low density lipoprotein receptor-related protein 6 (LRP6), a wnt co-receptor, regulates multiple functions in various organs. However, the roles of LRP6 in the adult heart are not well understood. Methods: We observed LRP6 expression in heart with end-stage dilated cardiomyopathy (DCM) by western blot. Tamoxifen-inducible cardiac-specific LRP6 knockout mouse was constructed. Hemodynamic and echocardiographic analyses were performed to these mice. Results: Cardiac LRP6 expression was dramatically decreased in patients with end-stage dilated cardiomyopathy (DCM) compared to control group...
2018: Theranostics
https://www.readbyqxmd.com/read/29343573/porcine-mx1-protein-inhibits-classical-swine-fever-virus-replication-by-targeting-nonstructural-protein-ns5b
#3
Jing Zhou, Jing Chen, Xiao-Min Zhang, Zhi-Can Gao, Chun-Chun Liu, Yun-Na Zhang, Jin-Xiu Hou, Zhao-Yao Li, Lin Kan, Wen-Liang Li, Bin Zhou
Mx proteins are interferon-induced GTPases that have broad antiviral activity against a wide range of RNA and DNA viruses; they belong to the dynamin superfamily of large GTPases. In this study, we confirmed the anti-CSFV activity of porcine Mx1 in vitro and showed that porcine Mx2 (poMx2), human MxA (huMxA), and mouse Mx1 (mmMx1) also have anti-CSFV activity in vitro. siRNA experiments revealed that depletion of endogenous poMx1 or poMx2 enhanced CSFV replication, suggesting that porcine Mx proteins are responsible for the antiviral activity of interferon-α (IFNα) against CSFV infection...
January 17, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29340645/a-plasma-metabolomic-signature-involving-purine-metabolism-in-human-optic-atrophy-1-opa1-related-disorders
#4
Cinzia Bocca, Judith Kouassi Nzoughet, Stéphanie Leruez, Patrizia Amati-Bonneau, Marc Ferré, Mariame-Selma Kane, Charlotte Veyrat-Durebex, Juan Manuel Chao de la Barca, Arnaud Chevrollier, Chadi Homedan, Christophe Verny, Dan Miléa, Vincent Procaccio, Gilles Simard, Dominique Bonneau, Guy Lenaers, Pascal Reynier
Purpose: Dominant optic atrophy (DOA; MIM [Mendelian Inheritance in Man] 165500), resulting in retinal ganglion cell degeneration, is mainly caused by mutations in the optic atrophy 1 (OPA1) gene, which encodes a dynamin guanosine triphosphate (GTP)ase involved in mitochondrial membrane processing. This work aimed at determining whether plasma from OPA1 pathogenic variant carriers displays a specific metabolic signature. Methods: We applied a nontargeted clinical metabolomics pipeline based on ultra-high-pressure liquid chromatography coupled to high-resolution mass spectrometry (UHPLC-HRMS) allowing the exploration of 500 polar metabolites in plasma...
January 1, 2018: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/29336470/tnf-%C3%AE-induces-drp1-mediated-mitochondrial-fragmentation-during-inflammatory-cardiomyocyte-injury
#5
Yue-Liang Shen, Ying-Zhou Shi, Gai-Ge Chen, Lin-Lin Wang, Ming-Zhi Zheng, Hong-Feng Jin, Ying-Ying Chen
Dynamin-related peptide 1 (Drpl)-mediated mitochondrial fission is an important process associated with cardiac dysfunction under different pathological conditions. The aim of the present study was to investigate the expression of Drpl during inflammatory myocardial injury. Sprague‑Dawley rats were treated intraperitoneally with lipopolysaccharides (LPS). Furthermore, cultured H9C2 cardiomyocytes were treated with LPS, interleukin‑6 (IL‑6) and tumor necrosis factor‑α (TNF‑α). Total and mitochondrial proteins were isolated from the heart tissue of rats and from the H9C2 cardiomyocytes...
January 15, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29330299/effects-of-allelic-variations-in-the-human-myxovirus-resistance-protein-a-on-its-antiviral-activity
#6
Laura Graf, Alexej Dick, Franziska Sendker, Emanuel Barth, Manja Marz, Oliver Daumke, Georg Kochs
Only a minority of patients infected with seasonal influenza A viruses exhibits a severe or fatal outcome of infection, but the reasons for this inter-individual variability in influenza susceptibility are unclear. To gain further insights into the molecular mechanisms underlying this variability, we investigated naturally occurring allelic variations of the myxovirus resistance 1 (MX1) gene coding for the influenza restriction factor MxA. The interferon-induced dynamin-like GTPase consists of an N-terminal GTPase domain, a bundle signaling element, and a C-terminal stalk responsible for oligomerization and viral target recognition...
January 12, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29329364/downregulation-of-drp1-a-fission-regulator-is-associated-with-human-lung-and-colon-cancers
#7
Young Yeon Kim, Seong-Hoon Yun, Jeanho Yun
Dynamin-related protein 1 (Drp1), a dynamin-related GTPase, is a key regulator of mitochondrial fission. Although recent studies have shown that Drp1 plays important roles in various important cellular processes, such as maintaining proper mitochondrial function, apoptosis and necrosis, the potential involvement of Drp1 in cancer development has not been fully addressed. To explore the role of Drp1 in cancer, we examined Drp1 levels in various human cancer tissues. Tissue array analysis showed that the level of Drp1 was decreased significantly in malignant colon and lung cancer tissues, whereas no change in Drp1 was observed in breast and prostate tumors...
January 10, 2018: Acta Biochimica et Biophysica Sinica
https://www.readbyqxmd.com/read/29320741/endocytosis-of-katp-channels-drives-glucose-stimulated-excitation-of-pancreatic-%C3%AE-cells
#8
Young-Eun Han, Jung Nyeo Chun, Min Jeong Kwon, Young-Sun Ji, Myong-Ho Jeong, Hye-Hyun Kim, Sun-Hyun Park, Jong Cheol Rah, Jong-Sun Kang, Suk-Ho Lee, Won-Kyung Ho
Insulin secretion from pancreatic β cells in response to high glucose (HG) critically depends on the inhibition of KATP channel activity in HG. It is generally believed that HG-induced effects are mediated by the increase in intracellular ATP, but here, we showed that, in INS-1 cells, endocytosis of KATP channel plays a major role. Upon HG stimulation, resting membrane potential depolarized by 30.6 mV (from -69.2 to -38.6 mV) and KATP conductance decreased by 91% (from 0.243 to 0.022 nS/pF), whereas intracellular ATP was increased by only 47%...
January 9, 2018: Cell Reports
https://www.readbyqxmd.com/read/29314417/a-nestin-cdk5-drp1-axis-regulates-neural-stem-progenitor-cell-stemness-via-a-metabolic-shift
#9
Jiancheng Wang, Yinong Huang, Jianye Cai, Qiong Ke, Jiaqi Xiao, Weijun Huang, Hongyu Li, Yuan Qiu, Yi Wang, Bin Zhang, Haoxiang Wu, Yanan Zhang, Xin Sui, Adham Sameer A Bardeesi, Andy Peng Xiang
Neural stem/progenitor cells (NSPCs) transplantation provides an alternative approach for various central nervous system (CNS) diseases treatment, while the difficulties in NSPC acquisition and expansion limit their further application. Unveiling the mechanism of NSPC stemness regulation may contribute to its further application. Nestin, generally recognized as a marker of NSPCs, plays a crucial role in the CNS development and NSPC stemness maintenance. Here, we report that Nestin loss triggers mitochondrial network remodeling and enhances oxidative phosphorylation (OXPHOS) in NSPCs treated with Nestin RNA interference (RNAi)...
January 3, 2018: Stem Cells
https://www.readbyqxmd.com/read/29313986/protein-kinase-d-activation-induces-mitochondrial-fragmentation-and-dysfunction-in-cardiomyocytes
#10
Bong Sook Jhun, Jin O-Uchi, Stephanie M Adaniya, Tomas J Mancini, Jessica L Cao, Michelle E King, Amy K Landi, Hanley Ma, Milla Shin, Donqin Yang, Xiaole Xu, Yisang Yoon, Gaurav Choudhary, Richard T Clements, Ulrike Mende, Shey-Shing Sheu
Regulation of mitochondrial morphology is crucial for the maintenance of physiological functions in many cell types including cardiomyocytes. Small and fragmented mitochondria are frequently observed in pathological condition, but it is still unclear which cardiac signalling pathway is responsible for regulating the abnormal mitochondrial morphology in cardiomyocytes. Here we demonstrate that a downstream kinase of Gq -protein coupled receptor (Gq PCR) signalling, protein kinase D (PKD), mediates pathophysiological modifications in mitochondrial morphology and function, which consequently contribute to the activation of apoptotic signalling...
January 5, 2018: Journal of Physiology
https://www.readbyqxmd.com/read/29307080/inhibition-of-peroxynitrite-induced-mitophagy-activation-attenuates-cerebral-ischemia-reperfusion-injury
#11
Jinghan Feng, Xingmiao Chen, Binghe Guan, Caiming Li, Jinhua Qiu, Jiangang Shen
Activated autophagy/mitophagy has been intensively observed in ischemic brain, but its roles remain controversial. Peroxynitrite (ONOO-), as a representative of reactive nitrogen species, is considered as a critical neurotoxic factor in mediating cerebral ischemia-reperfusion (I/R) injury, but its roles in autophagy/mitophagy activation remain unclear. Herein, we hypothesized that ONOO- could induce PINK1/Parkin-mediated mitophagy activation via triggering dynamin-related protein 1 (Drp1) recruitment to damaged mitochondria, contributing to cerebral I/R injury...
January 6, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29301943/first-person-avinash-persaud
#12
(no author information available yet)
First Person is a series of interviews with the first authors of a selection of papers published in Journal of Cell Science, helping early-career researchers promote themselves alongside their papers. Avinash Persaud is the first author on 'Dynamin inhibitors block activation of mTORC1 by amino acids independently of dynamin', published in Journal of Cell Science. Avinash is a research associate in the lab of Daniela Rotin at The Hospital for Sick Children, Toronto, Canada, investigating mTORC1 signaling and the function of the ubiquitin ligase Nedd4...
January 4, 2018: Journal of Cell Science
https://www.readbyqxmd.com/read/29298696/enhanced-human-enterovirus-71-infection-by-endocytosis-inhibitors-reveals-multiple-entry-pathways-by-enterovirus-causing-hand-foot-and-mouth-diseases
#13
Meichun Yuan, Jingjing Yan, Jingna Xun, Chong Chen, Yuling Zhang, Min Wang, Wenqi Chu, Zhigang Song, Yunwen Hu, Shuye Zhang, Xiaoyan Zhang
BACKGROUND: Human enterovirus 71 (EV71) was previously known to enter cells through clathrin or caveolar mediated endocytic pathways. However, we observed chlorpromazine (CPZ) or dynasore (DNS), which inhibit clathrin and dynamin mediated endocytosis, did not suppress EV71 cell entry in particular cell types. So the current knowledge of entry mechanisms by EV71 is not complete. METHODS: Viral infection was examined by flow cytometry or end-point dilution assays...
January 3, 2018: Virology Journal
https://www.readbyqxmd.com/read/29296945/the-class-i-scavenger-receptor-cd163-promotes-internalization-of-adamts13-by-macrophages
#14
Fabian C Verbij, Nicoletta Sorvillo, Paul H P Kaijen, Johana Hrdinova, Ivan Peyron, Rob Fijnheer, Anja Ten Brinke, Alexander B Meijer, Floris P J van Alphen, Timo K van den Berg, Jonas J H Graversen, Soren K Moestrup, Jan Voorberg
Internalization of ADAMTS13 by macrophages may contribute to its clearance from the circulation. Here we investigated endocytic mechanisms that contribute to the uptake of ADAMTS13 by macrophages. Human monocyte-derived macrophages were used to monitor the uptake of fluorescently labeled recombinant ADAMTS13 by flow cytometry. Internalization of ADAMTS13 was blocked upon addition of the cell-permeable dynamin inhibitor dynasore. Partial blocking of ADAMTS13 uptake was observed by using mannan; however, uptake was not affected by an antibody that blocked binding to the macrophage mannose receptor CD206, which suggests that other endocytic receptors contribute to the internalization of ADAMTS13 by macrophages...
January 24, 2017: Blood Advances
https://www.readbyqxmd.com/read/29276520/combined-15n-labeling-and-tandemmoac-quantifies-phosphorylation-of-map-kinase-substrates-downstream-of-mkk7-in-arabidopsis
#15
Nicola V Huck, Franz Leissing, Petra Majovsky, Matthias Buntru, Christina Aretz, Mirkko Flecken, Jörg P J Müller, Simon Vogel, Stefan Schillberg, Wolfgang Hoehenwarter, Uwe Conrath, Gerold J M Beckers
Reversible protein phosphorylation is a widespread posttranslational modification that plays a key role in eukaryotic signal transduction. Due to the dynamics of protein abundance, low stoichiometry and transient nature of protein phosphorylation, the detection and accurate quantification of substrate phosphorylation by protein kinases remains a challenge in phosphoproteome research. Here, we combine tandem metal-oxide affinity chromatography (tandemMOAC) with stable isotope 15N metabolic labeling for the measurement and accurate quantification of low abundant, transiently phosphorylated peptides by mass spectrometry...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/29246969/allele-specific-silencing-therapy-for-dynamin-2-related-dominant-centronuclear-myopathy
#16
Delphine Trochet, Bernard Prudhon, Maud Beuvin, Cécile Peccate, Stéphanie Lorain, Laura Julien, Sofia Benkhelifa-Ziyyat, Aymen Rabai, Kamel Mamchaoui, Arnaud Ferry, Jocelyn Laporte, Pascale Guicheney, Stéphane Vassilopoulos, Marc Bitoun
Rapid advances in allele-specific silencing by RNA interference established a strategy of choice to cure dominant inherited diseases by targeting mutant alleles. We used this strategy for autosomal-dominant centronuclear myopathy (CNM), a rare neuromuscular disorder without available treatment due to heterozygous mutations in the DNM2 gene encoding Dynamin 2. Allele-specific siRNA sequences were developed in order to specifically knock down the human and murine DNM2-mRNA harbouring the p.R465W mutation without affecting the wild-type allele...
December 15, 2017: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/29245958/apelin-protects-against-myocardial-ischemic-injury-by-inhibiting-dynamin-related-protein-1
#17
Wei Xu, Hongwei Yu, Ruixue Ma, Lina Ma, Qiushuang Liu, Huitong Shan, Chengyu Wu, Rong Zhang, Yuhong Zhou, Hongli Shan
It is known that dynamin-related protein 1 (Drp1)-mediated mitochondrial fission plays an important role in ischemic injury of myocardial infarction (MI). Apelin, an endogenous ligand for Apelin receptor, acts as a key modulator of cardiovascular diseases. Here, we examined the effects of Apelin on MI injury and underlying mechanisms. Adult male C57BL/6J mice were treated with Apelin for 4 weeks and then subjected coronary artery ligation (LAD) to induce MI and the protective effects of Apelin on MI injury were evaluated at 6 h post LAD...
November 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/29245943/saikosaponin-d-a-calcium-mobilizing-agent-sensitizes-chemoresistant-ovarian-cancer-cells-to-cisplatin-induced-apoptosis-by-facilitating-mitochondrial-fission-and-g2-m-arrest
#18
Hideaki Tsuyoshi, Vincent Kam Wai Wong, Yu Han, Makoto Orisaka, Yoshio Yoshida, Benjamin K Tsang
Cisplatin (CDDP) and its derivatives are first line anti-cancer drugs for ovarian cancer (OVCA). However, chemoresistance due to high incidence of p53 mutations leads to poor clinical prognosis. Saikosaponin-d (Ssd), a saponin from a herbal plant extract, has been shown to induce cell death and sensitize chemoresistant cells to chemotherapeutic agents. Here, we demonstrated that Ssd sensitized chemoresistant OVCA cells with either p53-wt, -mutant and -null to CDDP. The action of Ssd appears to be through induction of mitochondrial fragmentation and G2/M arrest...
November 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/29241732/pgam5-regulates-pink1-parkin-mediated-mitophagy-via-drp1-in-cccp-induced-mitochondrial-dysfunction
#19
Yun Sun Park, Su Eun Choi, Hyun Chul Koh
Mitochondrial dynamics and mitophagy are critical processes for regulating mitochondrial homeostasis. Phosphoglycerate mutase family member 5 (PGAM5) is a mitochondrial protein that plays crucial roles in apoptosis and necroptosis, but the roles of PGAM5 in mitochondrial dynamics and mitophagy remain unclear. In this study, we investigated the role of PGAM5 in carbonyl cyanide m-chlorophenylhydrazone (CCCP)-induced mitochondrial damage and the correlation between mitochondrial dynamics and mitophagy using SH-SY5Y cells...
December 11, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/29239787/deciphering-psoriasis-a-bioinformatic-approach
#20
Juan L Melero, Sergi Andrades, Lluís Arola, Antoni Romeu
BACKGROUND: Psoriasis is an immune-mediated, inflammatory and hyperproliferative disease of the skin and joints. The cause of psoriasis is still unknown. The fundamental feature of the disease is the hyperproliferation of keratinocytes and the recruitment of cells from the immune system in the region of the affected skin, which leads to deregulation of many well-known gene expressions. OBJECTIVE: Based on data mining and bioinformatic scripting, here we show a new dimension of the effect of psoriasis at the genomic level...
November 22, 2017: Journal of Dermatological Science
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