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https://www.readbyqxmd.com/read/28828145/apigenin-alleviates-endotoxin-induced-myocardial-toxicity-by-modulating-inflammation-oxidative-stress-and-autophagy
#1
Fang Li, Fangfang Lang, Huilin Zhang, Liangdong Xu, Yidan Wang, Chunxiao Zhai, Enkui Hao
Apigenin, a component in daily diets, demonstrates antioxidant and anti-inflammatory properties. Here, we intended to explore the mechanism of apigenin-mediated endotoxin-induced myocardial injury and its role in the interplay among inflammation, oxidative stress, and autophagy. In our lipopolysaccharide- (LPS-) induced myocardial injury model, apigenin ameliorated cardiac injury (lactate dehydrogenase (LDH) and creatine kinase (CK)), cell death (TUNEL staining, DNA fragmentation, and PARP activity), and tissue damage (cardiac troponin I (cTnI) and cardiac myosin light chain-1 (cMLC1)) and improved cardiac function (ejection fraction (EF) and end diastolic left ventricular inner dimension (LVID))...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28827819/the-effects-of-dexamethasone-administered-during-pregnancy-on-the-postpartum-spiny-mouse-ovary
#2
Monika Hułas-Stasiak, Piotr Dobrowolski, Bożena Pawlikowska-Pawlęga, Ewa Tomaszewska, Siemowit Muszyński
Excessive exposure to glucocorticoids can alter ovarian function by modulating oogenesis, folliculogenesis and steroidogenesis. The aim of the present study was to examine the effects of dexamethasone (DEX) administered during pregnancy on folliculogenesis and corpus luteum development in the postpartum spiny mouse ovary. DEX (125 μg kg-1 body weight per day) was applied to pregnant spiny mouse from day 20 of gestation to parturition. The obtained ovaries were fixed and used for immunohistochemistry and TEM analysis...
2017: PloS One
https://www.readbyqxmd.com/read/28814521/hiv-fusion-in-dendritic-cells-mainly-occurs-at-the-surface-and-is-limited-by-low-cd4-levels
#3
Lise Chauveau, Daniel Aaron Donahue, Blandine Monel, Francoise Porrot, Timothée Bruel, Lea Richard, Nicoletta Casartelli, Olivier Schwartz
HIV-1 poorly infects monocyte-derived dendritic cells (MDDCs). This is in a large part due to SAMHD1, which restricts viral reverse transcription. Pseudotyping HIV-1 with VSV-G strongly enhances infection, suggesting that earlier steps of viral replication, including fusion, are also inefficient in MDDCs. The site of HIV-1 fusion remains controversial and may depend on the cell type, with reports indicating that it occurs at the plasma membrane or contrarily, in an endocytic compartment. Here, we examined the pathways of HIV-1 entry in MDDCs...
August 16, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28806745/persistent-mycobacteria-evade-an-antibacterial-program-mediated-by-phagolysosomal-tlr7-8-myd88-in-human-primary-macrophages
#4
Alexandre Gidon, Signe Elisabeth Åsberg, Claire Louet, Liv Ryan, Markus Haug, Trude Helen Flo
Pathogenic mycobacteria reside in macrophages where they avoid lysosomal targeting and degradation through poorly understood mechanisms proposed to involve arrest of phagosomal maturation at an early endosomal stage. A clear understanding of how this relates to host defenses elicited from various intracellular compartments is also missing and can only be studied using techniques allowing single cell and subcellular analyses. Using confocal imaging of human primary macrophages infected with Mycobacterium avium (Mav) we show evidence that Mav phagosomes are not arrested at an early endosomal stage, but mature to a (LAMP1+/LAMP2+/CD63+) late endosomal/phagolysosomal stage where inflammatory signaling and Mav growth restriction is initiated through a mechanism involving Toll-like receptors (TLR) 7 and 8, the adaptor MyD88 and transcription factors NF-κB and IRF-1...
August 14, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28802408/down-regulation-of-malate-synthase-in-mycobacterium-tuberculosis-h37ra-leads-to-reduced-stress-tolerance-persistence-and-survival-in-macrophages
#5
Kumar Sachin Singh, Rishabh Sharma, Deepa Keshari, Nirbhay Singh, Sudheer Kumar Singh
Malate synthase is a condensing enzyme responsible for conversion of glyoxylate to malate in the presence of acetyl-CoA. This reaction helps in bypassing the TCA cycle reactions involving carbon loss and leads to diverting some of the carbon skeletons to gluconeogenic events while rest can continue to provide TCA cycle intermediates. Malate synthase (GlcB) is encoded by MRA_1848 of Mycobacterium tuberculosis H37Ra (Mtb-Ra). We developed a knockdown (KD) Mtb-Ra strain by down-regulating GlcB. The survival studies suggested increased susceptibility to oxidative and nitrosative stress as well as to rifampicin...
September 2017: Tuberculosis
https://www.readbyqxmd.com/read/28751712/activation-of-mitophagy-leads-to-decline-in-mfn2-and-loss-of-mitochondrial-mass-in-fuchs-endothelial-corneal-dystrophy
#6
Anne-Sophie Benischke, Shivakumar Vasanth, Takashi Miyai, Kishore Reddy Katikireddy, Tomas White, Yuming Chen, Adna Halilovic, Marianne Price, Francis Price, Paloma B Liton, Ula V Jurkunas
Human corneal endothelial cells (HCEnCs) are terminally differentiated cells that have limited regenerative potential. The large numbers of mitochondria in HCEnCs are critical for pump and barrier function required for corneal hydration and transparency. Fuchs Endothelial Corneal Dystrophy (FECD) is a highly prevalent late-onset oxidative stress disorder characterized by progressive loss of HCEnCs. We previously reported increased mitochondrial fragmentation and reduced ATP and mtDNA copy number in FECD. Herein, carbonyl cyanide m-chlorophenyl hydrazone (CCCP)-induced mitochondrial depolarization decreased mitochondrial mass and Mfn2 levels, which were rescued with mitophagy blocker, bafilomycin, in FECD...
July 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28743755/ubiquitination-of-exposed-glycoproteins-by-scf-fbxo27-directs-damaged-lysosomes-for-autophagy
#7
Yukiko Yoshida, Sayaka Yasuda, Toshiharu Fujita, Maho Hamasaki, Arisa Murakami, Junko Kawawaki, Kazuhiro Iwai, Yasushi Saeki, Tamotsu Yoshimori, Noriyuki Matsuda, Keiji Tanaka
Ubiquitination functions as a signal to recruit autophagic machinery to damaged organelles and induce their clearance. Here, we report the characterization of FBXO27, a glycoprotein-specific F-box protein that is part of the SCF (SKP1/CUL1/F-box protein) ubiquitin ligase complex, and demonstrate that SCF(FBXO27) ubiquitinates glycoproteins in damaged lysosomes to regulate autophagic machinery recruitment. Unlike F-box proteins in other SCF complexes, FBXO27 is subject to N-myristoylation, which localizes it to membranes, allowing it to accumulate rapidly around damaged lysosomes...
July 25, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28732201/small-molecules-for-early-endosome-specific-patch-clamping
#8
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/28720712/regulation-of-the-autophagy-system-during-chronic-contractile-activity-induced-muscle-adaptations
#9
Yuho Kim, David A Hood
Skeletal muscle is adaptable to exercise stimuli via the upregulation of mitochondrial biogenesis, and recent studies have suggested that autophagy also plays a role in exercise-induced muscle adaptations. However, it is still obscure how muscle regulates autophagy over the time course of training adaptations. This study examined the expression of autophagic proteins in skeletal muscle of rats exposed to chronic contractile activity (CCA; 6 h/day, 9V, 10 Hz continuous, 0.1 msec pulse duration) for 1, 3, and 7 days (n = 8/group)...
July 2017: Physiological Reports
https://www.readbyqxmd.com/read/28687162/altered-expression-of-lysosomal-associated-membrane-protein-1-in-esophageal-squamous-cell-carcinoma
#10
Jian Huang, Lei Li, Jianli Liu, Juan Yu, Xiaoxiao Wu, Ying Xu, Ming Ma, Wei Wang, Renya Zhang
BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is one of the most common cancers. LAMP1, major protein components of lysosome, is primarily located on the lysosomal membrane and rarely expressed on the surface of normal cells, playing an important role in the lysosome-mediated physiological processes. Previous studies confirmed that LAMP1 showed high expression in astrocytoma. The purpose of this study was to investigate the expression levels of LAMP1 and to discuss its roles in ESCC...
August 2017: Pathology, Research and Practice
https://www.readbyqxmd.com/read/28685385/exclusive-activation-of-caspase-3-in-mossy-fibers-and-altered-dynamics-of-autophagy-markers-in-the-mice-hippocampus-upon-status-epilepticus-induced-by-kainic-acid
#11
A Rami, A Benz
Epileptic seizures are generally associated with pathological changes in the hippocampus such as astrogliosis, mossy fiber sprouting, and neuronal damage. However, more than 30% of temporal lobe epilepsy in humans shows neither neuronal damage nor mossy fiber sprouting despite chronic epileptic seizures. A similar situation exists in certain commonly used strains of mice, specifically C57BL/6 and BALB/c, which exhibit epileptic seizures, but no neuronal damage upon kainic acid administration. This suggests that intrinsic factors may influence the pathological manifestations of epilepsy...
July 6, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28679759/mutational-analysis-of-lassa-virus-glycoprotein-highlights-regions-required-for-alpha-dystroglycan-utilization
#12
Marissa Acciani, Jacob T Alston, Guohui Zhao, Hayley Reynolds, Afroze M Ali, Brian Xu, Melinda A Brindley
Lassa virus (LASV) is an enveloped RNA virus endemic to West Africa and responsible for severe cases of hemorrhagic fever. Virus entry is mediated by the glycoprotein complex consisting of a stable signal peptide, a receptor-binding subunit GP1, and a viral-host membrane fusion subunit GP2. Several cellular receptors can interact with the GP1 subunit and mediate viral entry, including alpha-dystroglycan (αDG) and lysosomal associated membrane protein 1 (LAMP1). In order to define the regions within GP1 that interact with the cellular receptors, we implemented insertional mutagenesis, carbohydrate shielding, and alanine scanning mutagenesis...
July 5, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28677644/2bc-non-structural-protein-of-enterovirus-a71-interacts-with-snare-proteins-to-trigger-autolysosome-formation
#13
Jeffrey K F Lai, I-Ching Sam, Pauline Verlhac, Joël Baguet, Eeva-Liisa Eskelinen, Mathias Faure, Yoke Fun Chan
Viruses have evolved unique strategies to evade or subvert autophagy machinery. Enterovirus A71 (EV-A71) induces autophagy during infection in vitro and in vivo. In this study, we report that EV-A71 triggers autolysosome formation during infection in human rhabdomyosarcoma (RD) cells to facilitate its replication. Blocking autophagosome-lysosome fusion with chloroquine inhibited virus RNA replication, resulting in lower viral titres, viral RNA copies and viral proteins. Overexpression of the non-structural protein 2BC of EV-A71 induced autolysosome formation...
July 4, 2017: Viruses
https://www.readbyqxmd.com/read/28650977/leishmania-donovani-resides-in-modified-early-endosomes-by-upregulating-rab5a-expression-via-the-downregulation-of-mir-494
#14
Jitender Kumar Verma, Ruchir Rastogi, Amitabha Mukhopadhyay
Several intracellular pathogens arrest the phagosome maturation in the host cells to avoid transport to lysosomes. In contrast, the Leishmania containing parasitophorous vacuole (PV) is shown to recruit lysosomal markers and thus Leishmania is postulated to be residing in the phagolysosomes in macrophages. Here, we report that Leishmania donovani specifically upregulates the expression of Rab5a by degrading c-Jun via their metalloprotease gp63 to downregulate the expression of miR-494 in THP-1 differentiated human macrophages...
June 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28647341/suppression-of-autophagic-flux-contributes-to-cardiomyocyte-death-by-activation-of-necroptotic-pathways
#15
Makoto Ogasawara, Toshiyuki Yano, Masaya Tanno, Koki Abe, Satoko Ishikawa, Takayuki Miki, Atsushi Kuno, Toshiyuki Tobisawa, Shingo Muratsubaki, Kouhei Ohno, Yuki Tatekoshi, Kei Nakata, Wataru Ohwada, Tetsuji Miura
BACKGROUND: The role of necroptosis in myocardial injury has not been fully characterized. Here we examined roles of mitochondrial permeability transition pore (mPTP) and autophagy in necroptosis of cardiomyocytes. METHODS AND RESULTS: In H9c2 cells, necroptosis was induced by treatment with TNF-α (TNF) and z-VAD-fmk (zVAD) for 24h, and necroptotic death was determined by LDH release (as % of total). TNF/zVAD increased LDH release from 16.6±4.3% to 60.6±2.7%, and the LDH release was suppressed by necrostatin-1 (29...
June 21, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28639285/porphyrin-modified-trastuzumab-improves-efficacy-of-her2-targeted-photodynamic-therapy-of-gastric-cancer
#16
Barbara Korsak, Gabriela M Almeida, Sara Rocha, Carla Pereira, Nuno Mendes, Hugo Osório, Patrícia M R Pereira, João M M Rodrigues, Rudolf J Schneider, Bruno Sarmento, João P C Tomé, Carla Oliveira
Gastric cancer (GC) is the 3rd deadliest cancer worldwide, due to limited treatment options and late diagnosis. Human epidermal growth factor receptor-2 (HER2) is overexpressed in ∼20% of GC cases and anti-HER2 antibody trastuzumab in combination with conventional chemotherapy, is recognized as standard therapy for HER2-positive metastatic GC. This strategy improves GC patients' survival by 2-3 months, however its optimal results in breast cancer indicate that GC survival may be improved. A new photoimmunoconjugate was developed by conjugating a porphyrin with trastuzumab (Trast:Porph) for targeted photodynamic therapy in HER2-positive GC...
October 1, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28634871/rabies-virus-co-localizes-with-early-rab5-and-late-rab7-endosomal-proteins-in-neuronal-and-sh-sy5y-cells
#17
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/28611685/entosis-acts-as-a-novel-way-within-sertoli-cells-to-eliminate-spermatozoa-in-seminiferous-tubule
#18
Nisar Ahmed, Ping Yang, Yufei Huang, Hong Chen, Tengfei Liu, Lingling Wang, Fazul Nabi, Yi Liu, Qiusheng Chen
The present study was designed to investigate the hypothesis that in vivo entosis is a novel pathway for eliminating spermatozoa in the seminiferous tubules (ST) during hibernation of the Chinese soft-shelled turtle. Western blot analysis revealed that the expression of LAMP1 in the testis was significantly higher during hibernation than that during non-hibernation. Immunohistochemistry reaction showed that LAMP1-positive substance was distributed within the Sertoli cells of the testis. Further examination by transmission electron microscopy (TEM), many degraded spermatozoa being enwrapped within large entotic vacuoles in Sertoli cells...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28591131/visualization-of-early-influenza-a-virus-trafficking-in-human-dendritic-cells-using-sted-microscopy
#19
Faezzah Baharom, Oliver S Thomas, Rico Lepzien, Ira Mellman, Cécile Chalouni, Anna Smed-Sörensen
Influenza A viruses (IAV) primarily target respiratory epithelial cells, but can also replicate in immune cells, including human dendritic cells (DCs). Super-resolution microscopy provides a novel method of visualizing viral trafficking by overcoming the resolution limit imposed by conventional light microscopy, without the laborious sample preparation of electron microscopy. Using three-color Stimulated Emission Depletion (STED) microscopy, we visualized input IAV nucleoprotein (NP), early and late endosomal compartments (EEA1 and LAMP1 respectively), and HLA-DR (DC membrane/cytosol) by immunofluorescence in human DCs...
2017: PloS One
https://www.readbyqxmd.com/read/28586379/lamp-2-absence-interferes-with-plasma-membrane-repair-and-decreases-t-cruzi-host-cell-invasion
#20
Natália Fernanda Couto, Dina Pedersane, Luisa Rezende, Patrícia P Dias, Tayanne L Corbani, Lívia C Bentini, Anny C S Oliveira, Ludmila F Kelles, Thiago Castro-Gomes, Luciana O Andrade
Trypanosoma cruzi enters host cells by subverting the mechanism of cell membrane repair. In this process, the parasite induces small injuries in the host cell membrane leading to calcium entry and lysosomal exocytosis, which are followed by compensatory endocytosis events that drive parasites into host cells. We have previously shown that absence of both LAMP-1 and 2, major components of lysosomal membranes, decreases invasion of T. cruzi into host cells, but the mechanism by which they interfere with parasite invasion has not been described...
June 2017: PLoS Neglected Tropical Diseases
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