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https://www.readbyqxmd.com/read/28230856/ginsenoside-rg5-increases-cardiomyocyte-resistance-to-ischemic-injury-through-regulation-of-mitochondrial-hexokinase-ii-and-dynamin-related-protein-1
#1
Yi-Lin Yang, Jia Li, Kang Liu, Lei Zhang, Qun Liu, Baolin Liu, Lian-Wen Qi
Hexokinase-II (HK-II) and dynamin-related protein 1 (Drp1) regulate mitochondrial function differently. This study was designed to investigate the cardioprotective effect of ginsenoside Rg5 (Rg5) with emphasis on the regulation of mitochondrial HK-II and Drp1. Saturated acid palmitate (PA) stimulation increased lactate accumulation and induced cellular acidification by impairing the activity of pyruvate dehydrogenase (PDH) in cardiomyocytes, leading to HK-II dissociation from mitochondria. Rg5 improved PDH activity and prevented cellular acidification by combating fatty-acid oxidation, contributing to protecting mitochondrial HK-II...
February 23, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28230651/hypoxia-induces-internalization-of-%C3%AE%C2%BA-opioid-receptor
#2
Chunhua Xi, Xuan Liang, Chunhua Chen, Hasan Babazada, Tianzuo Li, Renyu Liu
BACKGROUND: It has been demonstrated that κ-opioid receptor agonists can reduce hypoxia-ischemia brain injury in animal models. However, it is unclear how the κ-opioid receptor responds to hypoxia-ischemia. In the current study, the authors used an in vitro model of oxygen-glucose deprivation and reoxygenation to explore how κ-opioid receptors respond to hypoxia and reoxygenation. METHODS: Mouse neuroblastoma Neuro2A cells were stably transfected with mouse κ-opioid receptor-tdTomato fusion protein or Flag-tagged mouse κ-opioid receptor, divided into several groups (n = 6 to 12), and used to investigate the κ-opioid receptor movement...
February 23, 2017: Anesthesiology
https://www.readbyqxmd.com/read/28228524/structural-insights-into-the-activation-mechanism-of-dynamin-like-ehd-atpases
#3
Arthur Alves Melo, Balachandra G Hegde, Claudio Shah, Elin Larsson, J Mario Isas, Séverine Kunz, Richard Lundmark, Ralf Langen, Oliver Daumke
Eps15 (epidermal growth factor receptor pathway substrate 15)-homology domain containing proteins (EHDs) comprise a family of dynamin-related mechano-chemical ATPases involved in cellular membrane trafficking. Previous studies have revealed the structure of the EHD2 dimer, but the molecular mechanisms of membrane recruitment and assembly have remained obscure. Here, we determined the crystal structure of an amino-terminally truncated EHD4 dimer. Compared with the EHD2 structure, the helical domains are 50° rotated relative to the GTPase domain...
February 22, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28228254/control-of-mitochondrial-remodeling-by-the-atpase-inhibitory-factor-1%C3%A2-unveils-a-pro-survival-relay-via-opa1
#4
Danilo Faccenda, Junji Nakamura, Giulia Gorini, Gurtej K Dhoot, Mauro Piacentini, Masusuke Yoshida, Michelangelo Campanella
The ubiquitously expressed ATPase inhibitory factor 1 (IF1) is a mitochondrial protein that blocks the reversal of the F1Fo-ATPsynthase, preventing dissipation of cellular ATP and ischemic damage. IF1 suppresses programmed cell death, enhancing tumor invasion and chemoresistance, and is expressed in various types of human cancers. In this study, we examined its effect on mitochondrial redox balance and apoptotic cristae remodeling, finding that, by maintaining ATP levels, IF1 reduces glutathione (GSH) consumption and inactivation of peroxiredoxin 3 (Prx3) during apoptosis...
February 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/28223496/ehd2-restrains-dynamics-of-caveolae-by-an-atp-dependent-membrane-bound-open-conformation
#5
Maria Hoernke, Jagan Mohan, Elin Larsson, Jeanette Blomberg, Dana Kahra, Sebastian Westenhoff, Christian Schwieger, Richard Lundmark
The EH-domain-containing protein 2 (EHD2) is a dynamin-related ATPase that confines caveolae to the cell surface by restricting the scission and subsequent endocytosis of these membrane pits. For this, EHD2 is thought to first bind to the membrane, then to oligomerize, and finally to detach, in a stringently regulated mechanistic cycle. It is still unclear how ATP is used in this process and whether membrane binding is coupled to conformational changes in the protein. Here, we show that the regulatory N-terminal residues and the EH domain keep the EHD2 dimer in an autoinhibited conformation in solution...
February 21, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28215578/mfn2-protects-dopaminergic-neurons-exposed-to-paraquat-both-in-vitro-and-in-vivo-implications-for-idiopathic-parkinson-s-disease
#6
Fanpeng Zhao, Wenzhang Wang, Chunyu Wang, Sandra L Siedlak, Hisashi Fujioka, Beisha Tang, Xiongwei Zhu
Mitochondrial dynamics and quality control plays a critical role in the maintenance of mitochondrial homeostasis and function. Pathogenic mutations of many genes associated with familial Parkinson's disease (PD) caused abnormal mitochondrial dynamics, suggesting a likely involvement of disturbed mitochondrial fission/fusion in the pathogenesis of PD. In this study, we focused on the potential role of mitochondrial fission/fusion in idiopathic PD patients and in neuronal cells and animals exposed to paraquat (PQ), a commonly used herbicide and PD-related neurotoxin, as models for idiopathic PD...
February 16, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28193781/real-time-imaging-of-sodium-glucose-transporter-sglt1-trafficking-and-activity-in-single-cells
#7
Chiara Ghezzi, Guillaume Calmettes, Pauline Morand, Bernard Ribalet, Scott John
The processes controlling targeting of glucose transporters to apical and basolateral membranes of polarized cells are complex and not-well understood. We have engineered SGLT1 and GLUT4 constructs linked to fluorescent proteins to highlight the differences in transporter expression and trafficking, in real time, in different cell types. Activity was assessed in parallel using a FRET glucose sensor. In COS cells and HEK cells, SGLT1 was distributed between the plasma membrane and intracellular compartments, but there was little expression in CHO cells...
February 2017: Physiological Reports
https://www.readbyqxmd.com/read/28191022/effect-of-mahuang-gancao-ganjiang-decoction-on-fusion-and-fission-of-mitochondria-and-apoptosis-of-lymphocytes-in-mice-under-cold-stress
#8
Longyun Chen, Huimin Chen
Mahuang Gancao Ganjiang Decoction (MGGD) can effectively alleviate the symptoms of the patients suffering from exogenous cold stress. However, the curative mechanism has not been fully clarified. This study was designed to investigate the effect of MGGD on the apoptosis of lymphocytes induced by cold stress in mice. The model mice were randomly divided into four groups: the normal control group (no handling mice), cold stress group, MGGD + cold stress group, and MGGD group. Lymphocytes of the mice were isolated from the peripheral blood...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/28190775/drp1-suppresses-leptin-and-glucose-sensing-of-pomc-neurons
#9
Anna Santoro, Michela Campolo, Chen Liu, Hiromi Sesaki, Rosaria Meli, Zhong-Wu Liu, Jung Dae Kim, Sabrina Diano
Hypothalamic pro-opiomelanocortin (POMC) neurons regulate energy and glucose metabolism. Intracellular mechanisms that enable these neurons to respond to changes in metabolic environment are ill defined. Here we show reduced expression of activated dynamin-related protein (pDRP1), a mitochondrial fission regulator, in POMC neurons of fed mice. These POMC neurons displayed increased mitochondrial size and aspect ratio compared to POMC neurons of fasted animals. Inducible deletion of DRP1 of mature POMC neurons (Drp1(fl/fl)-POMC-cre:ER(T2)) resulted in improved leptin sensitivity and glucose responsiveness...
January 30, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28188849/endocytosis-contributes-to-bmp2-induced-smad-signalling-and-neuronal-growth
#10
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...
February 8, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28185357/yeast-dynamin-interaction-with-escrt-proteins-at-the-endosome
#11
Bryan T Banh, Hyoeun McDermott, Sara Woodman, Shiva Kumar Goud Gadila, Uma Saimani, John Cw Short, Kyoungtae Kim
The dynamin-like protein, Vps1, is a GTPase involved in cargo sorting and membrane remodeling in multiple cellular trafficking pathways. Recently, Vps1 has been shown to genetically interact with ESCRT subunits. We tested the hypothesis that the functional connection of Vps1 with some of these subunits of ESCRT complexes occurs via a physical interaction. By utilizing the yeast two-hybrid system, we revealed that Vps1 physically interacts with the ESCRT-II subunits, Vps22 and Vps36, and the ESCRT-III subunit Vps24...
February 9, 2017: Cell Biology International
https://www.readbyqxmd.com/read/28179028/betanodavirus-like-particles-enter-host-cells-via-clathrin-mediated-endocytosis-in-a-cholesterol-ph-and-cytoskeleton-dependent-manner
#12
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/28174296/ncs1-regulates-ca2-dependent-focal-exocytosis-of-golgi-derived-vesicles-to-help-phagocytic-uptake-in-macrophages
#13
Nimi Vashi, Syed Bilal Ahmad Andrabi, Swapnil Ghanwat, Mrutyunjay Suar, Dhiraj Kumar
During phagocytic uptake by macrophages, role of Golgi apparatus was previously ruled out. Notably all such reports were limited to Fcγ-receptor mediated phagocytosis. Here we unravel a highly devolved mechanism for recruitment of Golgi-derived secretory vesicles during phagosome biogenesis, which was important for uptake of most cargos except IgG-coated ones. We report recruitment of Mannosidase-II positive Golgi-derived vesicles during uptake of diverse targets including latex beads, E. coli, Salmonella Typhimurium and Mycobacterium tuberculosis in human and mouse macrophages...
February 7, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28173848/inhibition-of-dynamin-related-protein-1-protects-against-myocardial-ischemia-reperfusion-injury-in-diabetic-mice
#14
Mingge Ding, Qianqian Dong, Zhenghua Liu, Zheng Liu, Yinxian Qu, Xing Li, Cong Huo, Xin Jia, Feng Fu, Xiaoming Wang
BACKGROUND: Many cardioprotective pharmacological agents failed to exert their protective effects in diabetic hearts subjected to myocardial ischemia/reperfusion (MI/R). Identify the molecular basis linking diabetes with MI/R injury is scientifically important and may provide effective therapeutic approaches. Dynamin-related protein 1 (Drp1)-mediated mitochondrial fission plays an important role in MI/R injury under non-diabetic conditions. Importantly, recent studies indicated that Drp1-mediated mitochondrial fission is enhanced in the myocardium of diabetic mice...
February 7, 2017: Cardiovascular Diabetology
https://www.readbyqxmd.com/read/28173111/reduced-dynamin-related-protein-1-protects-against-phosphorylated-tau-induced-mitochondrial-dysfunction-and-synaptic-damage-in-alzheimer-s-disease
#15
Ramesh Kandimalla, Maria Manczak, David Fry, Yeguvapalli Suneetha, Hiromi Sesaki, P Hemachandra Reddy
No abstract text is available yet for this article.
November 15, 2016: Human Molecular Genetics
https://www.readbyqxmd.com/read/28171750/crosstalk-between-clcb-dyn1-mediated-adaptive-clathrin-mediated-endocytosis-and-epidermal-growth-factor-receptor-signaling-increases-metastasis
#16
Ping-Hung Chen, Nawal Bendris, Yi-Jing Hsiao, Carlos R Reis, Marcel Mettlen, Hsuan-Yu Chen, Sung-Liang Yu, Sandra L Schmid
Signaling receptors are internalized and regulated by clathrin-mediated endocytosis (CME). Two clathrin light chain isoforms, CLCa and CLCb, are integral components of the endocytic machinery whose differential functions remain unknown. We report that CLCb is specifically upregulated in non-small-cell lung cancer (NSCLC) cells and is associated with poor patient prognosis. Engineered single CLCb-expressing NSCLC cells, as well as "switched" cells that predominantly express CLCb, exhibit increased rates of CME and altered clathrin-coated pit dynamics...
February 6, 2017: Developmental Cell
https://www.readbyqxmd.com/read/28163906/an-elisa-dyrk1a-non-radioactive-assay-suitable-for-the-characterization-of-inhibitors
#17
Yong Liu, Tatyana Adayev, Yu-Wen Hwang
The DYRK1A (dual specificity tyrosine phosphorylation-regulated kinase 1A) gene encodes a proline-directed Ser/Thr kinase. Elevated expression and/or altered distribution of the kinase have been implicated in the neurological impairments associated with Down syndrome (DS) and Alzheimer's disease (AD). Consequently, DYRK1A inhibition has been of significant interest as a potential strategy for therapeutic intervention of DS and AD. Many classes of novel inhibitors have been described in the past decade. Although non-radioactive methods for analyzing DYRK1A inhibition have been developed, methods employing radioactive tracers are still commonly used for quantitative characterization of DYRK1A inhibitors...
2017: F1000Research
https://www.readbyqxmd.com/read/28158302/host-cell-interactions-of-outer-membrane-vesicle-associated-virulence-factors-of-enterohemorrhagic-escherichia-coli-o157-intracellular-delivery-trafficking-and-mechanisms-of-cell-injury
#18
Martina Bielaszewska, Christian Rüter, Andreas Bauwens, Lilo Greune, Kevin-André Jarosch, Daniel Steil, Wenlan Zhang, Xiaohua He, Roland Lloubes, Angelika Fruth, Kwang Sik Kim, M Alexander Schmidt, Ulrich Dobrindt, Alexander Mellmann, Helge Karch
Outer membrane vesicles (OMVs) are important tools in bacterial virulence but their role in the pathogenesis of infections caused by enterohemorrhagic Escherichia coli (EHEC) O157, the leading cause of life-threatening hemolytic uremic syndrome, is poorly understood. Using proteomics, electron and confocal laser scanning microscopy, immunoblotting, and bioassays, we investigated OMVs secreted by EHEC O157 clinical isolates for virulence factors cargoes, interactions with pathogenetically relevant human cells, and mechanisms of cell injury...
February 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28154412/superresolution-imaging-identifies-that-conventional-trafficking-pathways-are-not-essential-for-endoplasmic-reticulum-to-outer-mitochondrial-membrane-protein-transport
#19
Kyle Salka, Shivaprasad Bhuvanendran, Kassandra Wilson, Petros Bozidis, Mansi Mehta, Kristin Rainey, Hiromi Sesaki, George H Patterson, Jyoti K Jaiswal, Anamaris M Colberg-Poley
Most nuclear-encoded mitochondrial proteins traffic from the cytosol to mitochondria. Some of these proteins localize at mitochondria-associated membranes (MAM), where mitochondria are closely apposed with the endoplasmic reticulum (ER). We have previously shown that the human cytomegalovirus signal-anchored protein known as viral mitochondria-localized inhibitor of apoptosis (vMIA) traffics from the ER to mitochondria and clusters at the outer mitochondrial membrane (OMM). Here, we have examined the host pathways by which vMIA traffics from the ER to mitochondria and clusters at the OMM...
December 2017: Scientific Reports
https://www.readbyqxmd.com/read/28154172/metabolic-alterations-contribute-to-enhanced-inflammatory-cytokine-production-in-irgm1-deficient-macrophages
#20
Elyse A Schmidt, Brian E Fee, Stanley C Henry, Amanda G Nichols, Mari L Shinohara, Jeffrey C Rathmell, Nancie J MacIver, Jörn Coers, Olga R Ilkayeva, Timothy R Koves, Gregory A Taylor
The Immunity-Related GTPases (IRG) are a family of proteins that are induced by interferon (IFN)-gamma and play pivotal roles in immune and inflammatory responses. IRGs ostensibly function as dynamin-like proteins that bind to intracellular membranes, and promote remodeling and trafficking of those membranes. Prior studies have shown that loss of Irgm1 in mice leads to increased lethality to bacterial infections, as well as enhanced inflammation to non-infectious stimuli; however, the mechanisms underlying these phenotypes are unclear...
February 1, 2017: Journal of Biological Chemistry
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