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https://www.readbyqxmd.com/read/28819214/hiv-1-nef-induced-cardiotoxicity-through-dysregulation-of-autophagy
#1
Manish K Gupta, Rafal Kaminski, Brian Mullen, Jennifer Gordon, Tricia H Burdo, Joseph Y Cheung, Arthur M Feldman, Muniswamy Madesh, Kamel Khalili
Cardiovascular disease is a leading cause of co-morbidity in HIV-1 positive patients, even those in whom plasma virus levels are well-controlled. The pathogenic mechanism of HIV-1-associated cardiomyopathy is unknown, but has been presumed to be mediated indirectly, owing to the absence of productive HIV-1 replication in cardiomyocytes. We sought to investigate the effect of the HIV-1 auxiliary protein, Nef, which is suspected of extracellular release by infected CD4+ T cells on protein quality control and autophagy in cardiomyocytes...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28762868/investigating-intracellular-persistence-of-staphylococcus-aureus-within-a-murine-alveolar-macrophage-cell-line
#2
A Lacoma, V Cano, D Moranta, V Regueiro, D Domínguez-Villanueva, M Laabei, M González-Nicolau, V Ausina, C Prat, J A Bengoechea
OBJECTIVE: Staphylococcus aureus is a particularly difficult pathogen to eradicate from the respiratory tract. Previous studies have highlighted the intracellular capacity of S.aureus in a number of phagocytic and non-phagocytic cells. The aim of this study was to define S.aureus interaction within a murine alveolar macrophage cell line. METHODS: Cell line MH-S was infected with Newman strain. Molecular mechanisms involved in phagocytosis were explored. To assess whether S...
August 1, 2017: Virulence
https://www.readbyqxmd.com/read/28734834/dynein-binds-and-stimulates-axonal-motility-of-the-endosome-adaptor-and-neep21-family-member-calcyon
#3
Liang Shi, Nagendran Muthusamy, Deanna Smith, Clare Bergson
The neuron-enriched, endosomal protein Calcyon (Caly) regulates endocytosis and vesicle sorting, and is important for synaptic plasticity and brain development. In the current investigation of Caly interacting proteins in brain, the microtubule retrograde motor subunit, cytoplasmic dynein 1 heavy chain (DYNC1H), and microtubule structural proteins, α and β tubulin, were identified as Caly associated proteins by MALDI-ToF/ToF. Direct interaction of the Caly-C terminus with dynein and tubulin was further confirmed in in vitro studies...
July 19, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/28732201/small-molecules-for-early-endosome-specific-patch-clamping
#4
Cheng-Chang Chen, Elisabeth S Butz, Yu-Kai Chao, Yulia Grishchuk, Lars Becker, Stefan Heller, Susan A Slaugenhaupt, Martin Biel, Christian Wahl-Schott, Christian Grimm
To resolve the subcellular distribution of endolysosomal ion channels, we have established a novel experimental approach to selectively patch clamp Rab5 positive early endosomes (EE) versus Rab7/LAMP1-positive late endosomes/lysosomes (LE/LY). To functionally characterize ion channels in endolysosomal membranes with the patch-clamp technique, it is important to develop techniques to selectively enlarge the respective organelles. We found here that two small molecules, wortmannin and latrunculin B, enlarge Rab5-positive EE when combined but not Rab7-, LAMP1-, or Rab11 (RE)-positive vesicles...
July 20, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/28726776/autophagosome-maturation-mediated-by-rab7-contributes-to-neuroprotection-of-hypoxic-preconditioning-against-global-cerebral-ischemia-in-rats
#5
Lixuan Zhan, Siyuan Chen, Kongping Li, Donghai Liang, Xinyong Zhu, Liu Liu, Zhiwei Lu, Weiwen Sun, En Xu
Autophagy disruption leads to neuronal damage in hypoxic-ischemic brain injury. Rab7, a member of the Rab GTPase superfamily, has a unique role in the regulation of autophagy. Hypoxic preconditioning (HPC) provides neuroprotection against transient global cerebral ischemia (tGCI). However, the underlying mechanisms remain poorly understood. Thus, the current study explored the potential molecular mechanism of the neuroprotective effect of HPC by investigating how Rab7 mediates autophagosome (AP) maturation after tGCI in adult rats...
July 20, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28724764/rab5-and-rab11-are-required-for-clathrin-dependent-endocytosis-of-japanese-encephalitis-virus-in-bhk-21-cells
#6
Chun-Chun Liu, Yun-Na Zhang, Zhao-Yao Li, Jin-Xiu Hou, Jing Zhou, Lin Kan, Bin Zhou, Pu-Yan Chen
During infection Japanese Encephalitis Virus generally enters host cells via receptor-mediated clathrin dependent endocytosis. The trafficking of JEV within endosomes is controlled by Rab GTPases, but which Rab proteins are involved in JEV entry into BHK-21 cells is unknown. In this study, entry and post-internalization of JEV were analyzed using biochemical inhibitors, RNA interference and dominant negative mutants. Our data demonstrate that JEV entry into BHK-21 cells depends on clathrin, dynamin, and cholesterol, but not caveolae or macropinocytosis...
July 19, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28720501/numb-positively-regulates-autophagic-flux-via-regulating-lysosomal-function
#7
Haiyan Sun, Yi Liu, Lei Zhang, Ximing Shao, Ke Liu, Zhihao Ding, Xianming Liu, Huashun Li, Hongchang Li
Autophagy is a lysosome-dependent catabolic process involving in the degradation and recycling of unnecessary or damaged proteins and organelles. Emerging evidence indicates that autophagy dysfunction is closely related to various human diseases including cancer, aging, myopathies and neurodegenerative disorders. Here, using genetic knockdown, we uncover the role of Numb, an endocytic adaptor protein, in regulating the late steps of autophagy. We found that Numb depletion led to the accumulation of autophagic vacuole, as verified by RFP-LC3 staining combined with transmission electron microscopy...
July 15, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28686604/boosting-efferocytosis-in-alveolar-space-using-bcg-vaccine-to-protect-host-against-influenza-pneumonia
#8
Sanjay Mukherjee, Renuka Subramaniam, Han Chen, Anthony Smith, Shiva Keshava, Homayoun Shams
Efferocytosis by alveolar phagocytes (APs) is pivotal in maintenance of lung homeostasis. Increased efferocytosis by APs results in protection against lethal acute lung injury due to pulmonary infections whereas defective efferocytosis by APs results in chronic lung inflammation. In this report, we show that pulmonary delivery of Bacillus Calmette-Guerin (BCG) significantly enhances efferocytosis by APs. Increased efferocytosis by APs maintains lung homeostasis and protects mice against lethal influenza pneumonia...
2017: PloS One
https://www.readbyqxmd.com/read/28665330/effects-of-epigallocatechin-3-gallate-on-autophagic-lipolysis-in-adipocytes
#9
Sang-Nam Kim, Hyun-Jung Kwon, Seun Akindehin, Hyun Woo Jeong, Yun-Hee Lee
Previous studies demonstrated effects of green tea on weight loss; however, green tea-induced modulation of adipocyte function is not fully understood. Here, we investigated effects of the major green tea phytochemical, epigallocatechin-3-gallate (EGCG) on triglyceride contents, lipolysis, mitochondrial function, and autophagy, in adipocytes differentiated from C₃H10T1/2 cells and immortalized pre-adipocytes in vitro. EGCG reduced the triglycerol content significantly in adipocytes by 25%, comparable to the nutrient starvation state...
June 30, 2017: Nutrients
https://www.readbyqxmd.com/read/28634871/rabies-virus-co-localizes-with-early-rab5-and-late-rab7-endosomal-proteins-in-neuronal-and-sh-sy5y-cells
#10
Waqas Ahmad, Yingying Li, Yidi Guo, Xinyu Wang, Ming Duan, Zhenhong Guan, Zengshan Liu, Maolin Zhang
Rabies virus (RABV) is a highly neurotropic virus that follows clathrin-mediated endocytosis and pH-dependent pathway for trafficking and invasion into endothelial cells. Early (Rab5, EEA1) and late (Rab7, LAMP1) endosomal proteins play critical roles in endosomal sorting, maturity and targeting various molecular cargoes, but their precise functions in the early stage of RABV neuronal infection remain elusive. In this study, the relationship between enigmatic entry of RABV with these endosomal proteins into neuronal and SH-SY5Y cells was investigated...
June 2017: Virologica Sinica
https://www.readbyqxmd.com/read/28634349/synuclein-impairs-trafficking-and-signaling-of-bdnf-in-a-mouse-model-of-parkinson-s-disease
#11
Fang Fang, Wanlin Yang, Jazmin B Florio, Edward Rockenstein, Brian Spencer, Xavier M Orain, Stephanie X Dong, Huayan Li, Xuqiao Chen, Kijung Sung, Robert A Rissman, Eliezer Masliah, Jianqing Ding, Chengbiao Wu
Recent studies have demonstrated that hyperphosphorylation of tau protein plays a role in neuronal toxicities of α-synuclein (ASYN) in neurodegenerative disease such as familial Alzheimer's disease (AD), dementia with Lewy bodies (DLB) and Parkinson's disease. Using a transgenic mouse model of Parkinson's disease (PD) that expresses GFP-ASYN driven by the PDGF-β promoter, we investigated how accumulation of ASYN impacted axonal function. We found that retrograde axonal trafficking of brain-derived neurotrophic factor (BDNF) in DIV7 cultures of E18 cortical neurons was markedly impaired at the embryonic stage, even though hyperphosphorylation of tau was not detectable in these neurons at this stage...
June 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28623232/the-ring-finger-and-pdz-domain-containing-protein-pdzrn3-controls-localization-of-the-mg-2-regulator-claudin-16-in-renal-tube-epithelial-cells
#12
Kana Marunaka, Chisa Furukawa, Naoko Fujii, Toru Kimura, Takumi Furuta, Toshiyuki Matsunaga, Satoshi Endo, Hajime Hasegawa, Naohiko Anzai, Yasuhiro Yamazaki, Masahiko Yamaguchi, Akira Ikari
Ion exchange in the renal tubules is fundamental to the maintenance of physiological ion levels. Claudin-16 (CLDN16) regulates the paracellular reabsorption of Mg(2+) in the thick ascending limb of Henle's loop in the kidney, with dephosphorylation of CLDN16 increasing its intracellular distribution and decreasing paracellular Mg(2+) permeability. CLDN16 is located in the tight junctions, but the mechanism regulating its localization is unclear. Using yeast two-hybrid systems, we found that CLDN16 binds to PDZRN3, a protein containing both RING-finger and PDZ domains...
August 4, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28600323/rab7-palmitoylation-is-required-for-efficient-endosome-to-tgn-trafficking
#13
Graziana Modica, Olga Skorobogata, Etienne Sauvageau, Adriano Vissa, Christopher M Yip, Peter K Kim, Hugo Wurtele, Stephane Lefrancois
Retromer is a multimeric protein complex that mediates endosome-to-TGN and endosome-to-plasma membrane trafficking of integral membrane proteins. Dysfunction of this complex has been linked to Alzheimer's and Parkinson's disease. The recruitment of retromer to endosomes is regulated by Rab7 to coordinate endosome-to- TGN trafficking of cargo-receptor complexes. Rab7 is also required for the degradation of internalized integral membrane proteins such as the epidermal growth factor receptor. We found that Rab7 is palmitoylated and that this modification is not required for membrane anchoring...
June 9, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28589907/improving-circulating-tumor-cells-enumeration-and-characterization-to-predict-outcome-in-first-line-chemotherapy-mcrpc-patients
#14
Luis León-Mateos, Helena Casas, Alicia Abalo, María Vieito, Manuel Abreu, Urbano Anido, Antonio Gómez-Tato, Rafael López, Miguel Abal, Laura Muinelo-Romay
INTRODUCTION: There is a critical need of new surrogate markers for improving the therapeutic selection and monitoring of metastatic prostate cancer patients. Nowadays clinical management of these patients is been driven by biochemical and clinical parameters without enough accuracy to allow a real personalized medicine. The present study was conducted to go insight the molecular profile of circulating tumor cells (CTCs) isolated from advanced metastatic castration-resistant prostate cancer (mCRPC) with the aim of identifying prognostic marker with potential utility for therapy selection and monitoring...
May 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/28588238/disruption-of-small-gtpase-rab7-exacerbates-the-severity-of-acute-pancreatitis-in-experimental-mouse-models
#15
Kenichi Takahashi, Hirosato Mashima, Kouichi Miura, Daichi Maeda, Akiteru Goto, Takashi Goto, Ge-Hong Sun-Wada, Yoh Wada, Hirohide Ohnishi
Although aberrations of intracellular vesicle transport systems towards lysosomes including autophagy and endocytosis are involved in the onset and progression of acute pancreatitis, the molecular mechanisms underlying such aberrations remain unclear. The pathways of autophagy and endocytosis are closely related, and Rab7 plays crucial roles in both. In this study, we analyzed the function of Rab7 in acute pancreatitis using pancreas-specific Rab7 knockout (Rab7(Δpan)) mice. In Rab7(Δpan) pancreatic acinar cells, the maturation steps of both endosomes and autophagosomes were deteriorated, and the lysosomal functions were affected...
June 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28570716/host-lipid-droplets-an-important-source-of-lipids-salvaged-by-the-intracellular-parasite-toxoplasma-gondii
#16
Sabrina J Nolan, Julia D Romano, Isabelle Coppens
Toxoplasma is an obligate intracellular parasite that replicates in mammalian cells within a parasitophorous vacuole (PV) that does not fuse with any host organelles. One mechanism developed by the parasite for nutrient acquisition is the attraction of host organelles to the PV. Here, we examined the exploitation of host lipid droplets (LD), ubiquitous fat storage organelles, by Toxoplasma. We show that Toxoplasma replication is reduced in host cells that are depleted of LD, or impaired in TAG lipolysis or fatty acid catabolism...
June 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28554874/free-cholesterol-accumulation-in-liver-sinusoidal-endothelial-cells-exacerbates-acetaminophen-hepatotoxicity-via-tlr9-signaling
#17
Toshiaki Teratani, Kengo Tomita, Takahiro Suzuki, Hirotaka Furuhashi, Rie Irie, Shigeaki Hida, Yoshikiyo Okada, Chie Kurihara, Hirotoshi Ebinuma, Nobuhiro Nakamoto, Hidetsugu Saito, Toshifumi Hibi, Soichiro Miura, Ryota Hokari, Takanori Kanai
BACKGROUND & AIMS: Although obesity is a risk factor for acute liver failure, the pathogenic mechanisms are not yet fully understood. High cholesterol (HC) intake, which often underlies obesity, is suggested to play a role in the mechanism. We aimed to elucidate the effect of HC diet on acetaminophen-induced acute liver injury, the most frequent cause of acute liver failure in the USA. METHODS: C57BL/6 Toll-like receptor 9 (TLR9) knockout (Tlr9(-/-)) mice and their Tlr9(+/+) littermates were fed an HC diet for 4 weeks and then treated with acetaminophen...
May 26, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28546026/the-crustin-like-peptide-plays-opposite-role-in-shrimp-immune-response-to-vibrio-alginolyticus-and-white-spot-syndrome-virus-wssv-infection
#18
Baozhen Sun, Zhi Wang, Fei Zhu
Crustin is an antimicrobial peptide (AMP) that plays a key role in innate immunity of crustaceans. In this study, we cloned the entire 660 bp crustin-like sequence with a 507 bp open reading frame encoding a 168 amino acid from Marsupenaeus japonicus. The crustin-like gene was primarily expressed in gills and over-expressed in shrimp hemocytes after challenge with WSSV or Vibrio alginolyticus. After knockdown crustin-like gene using specific double-stranded RNA (CRU-dsRNA), IMD, Rab7, L-lectin, mitogen-activated protein kinase, p53, prophenoloxidase and Rho were down-regulated and nitric oxide synthase, myosin and tumor necrosis factor-α were up-regulated in hemocytes at 24 h post dsRNA treatment...
July 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28539733/molecular-docking-of-phytoligands-to-the-viral-protein-receptor-p-monodon-rab7
#19
Jerrine Joseph, Raj Bhaskaran, Muthusamy Kaliraj, Muthiyah Muthuswamy, Arumugam Suresh
The development of shrimp aquaculture has been severely affected by viral diseases resulting in a huge economic burden to the industry. White spot disease (WSD) has caused severe mortality in farmed shrimp in many countries. Globally aquaculture industries face huge economic losses due to rapid spread of White Spot Syndrome Virus (WSSV) disease that can cause 100% mortality in a short period of 3-10 days. In the present study in order to prevent the spread of WSSV disease in shrimps, the receptor, PmRab7 has been chosen as the drug target...
2017: Bioinformation
https://www.readbyqxmd.com/read/28526875/endophilinas-regulate-endosomal-sorting-of-bdnf-trkb-to-mediate-survival-signaling-in-hippocampal-neurons
#20
Katja Burk, John D Murdoch, Siona Freytag, Melanie Koenig, Vinita Bharat, Ronja Markworth, Susanne Burkhardt, Andre Fischer, Camin Dean
The sorting of activated receptors into distinct endosomal compartments is essential to activate specific signaling cascades and cellular events including growth and survival. However, the proteins involved in this sorting are not well understood. We discovered a novel role of EndophilinAs in sorting of activated BDNF-TrkB receptors into late endosomal compartments. Mice lacking all three EndophilinAs accumulate Rab7-positive late endosomes. Moreover, EndophilinAs are differentially localized to, co-traffic with, and tubulate, distinct endosomal compartments: In response to BDNF, EndophilinA2 is recruited to both early and late endosomes, EndophilinA3 is recruited to Lamp1-positive late endosomes, and co-trafficks with Rab5 and Rab7 in both the presence and absence of BDNF, while EndophilinA1 colocalizes at lower levels with endosomes...
May 19, 2017: Scientific Reports
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