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https://www.readbyqxmd.com/read/28548877/role-of-osgin1-in-mediating-smoking-induced-autophagy-in-the-human-airway-epithelium
#1
Guoqing Wang, Haixia Zhou, Yael Strulovici-Barel, Mohammed Al-Hijji, Xuemei Ou, Jacqueline Salit, Matthew S Walters, Michelle R Staudt, Robert J Kaner, Ronald G Crystal
Enhanced macroautophagy/autophagy is recognized as a component of the pathogenesis of smoking-induced airway disease. Based on the knowledge that enhanced autophagy is linked to oxidative stress and the DNA damage response, both of which are linked to smoking, we used microarray analysis of the airway epithelium to identify smoking upregulated genes known to respond to oxidative stress and the DNA damage response. This analysis identified OSGIN1 (oxidative stress induced growth inhibitor 1) as significantly upregulated by smoking, in both the large and small airway epithelium, an observation confirmed by an independent small airway microarray cohort, TaqMan PCR of large and small airway samples and RNA-Seq of small airway samples...
May 26, 2017: Autophagy
https://www.readbyqxmd.com/read/28526875/endophilinas-regulate-endosomal-sorting-of-bdnf-trkb-to-mediate-survival-signaling-in-hippocampal-neurons
#2
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
https://www.readbyqxmd.com/read/28501505/sevoflurane-postconditioning-attenuates-reactive-astrogliosis-and-glial-scar-formation-after-ischemia-reperfusion-brain-injury
#3
Yong-Ming Zhu, Xue Gao, Yong Ni, Wei Li, Thomas A Kent, Shi-Gang Qiao, Chen Wang, Xiao-Xuan Xu, Hui-Ling Zhang
Cerebral ischemia leads to astrocyte's activation and glial scar formation. Glial scar can inhibit axonal regeneration during the recovery phase. It has demonstrated that sevoflurane has neuroprotective effects against ischemic stroke, but its effects on ischemia-induced formation of astrogliosis and glial scar are unknown. This study was designed to investigate the effect of sevoflurane postconditioning on astrogliosis and glial scar formation in ischemic stroke model both in vivo and in vitro. The results showed that 2...
May 10, 2017: Neuroscience
https://www.readbyqxmd.com/read/28475179/mtorc1-independent-autophagy-regulates-receptor-tyrosine-kinase-phosphorylation-in-colorectal-cancer-cells-via-an-mtorc2-mediated-mechanism
#4
Aikaterini Lampada, James O'Prey, Gyorgy Szabadkai, Kevin M Ryan, Daniel Hochhauser, Paolo Salomoni
The intracellular autophagic degradative pathway can have a tumour suppressive or tumour-promoting role depending on the stage of tumour development. Upon starvation or targeting of oncogenic receptor tyrosine kinases (RTKs), autophagy is activated owing to the inhibition of PI3K/AKT/mTORC1 signalling pathway and promotes survival, suggesting that autophagy is a relevant therapeutic target in these settings. However, the role of autophagy in cancer cells where the PI3K/AKT/mTORC1 pathway is constitutively active remains partially understood...
June 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28465362/bitter-melon-enhances-natural-killer-mediated-toxicity-against-head-and-neck-cancer-cells
#5
Sourav Bhattacharya, Naoshad Muhammd, Robert Steele, Jacki Kornbluth, Ratna B Ray
Natural Killer (NK) cells are one of the major components of innate immunity, with the ability to mediate antitumor activity. Understanding the role of NK cell mediated tumor killing in controling of solid tumor growth is still in the developmental stage. We have shown recently that bitter melon extract (BME) modulates the regulatory T cell (Treg) population in head and neck squamous cell carcinoma (HNSCC). However, the role of BME in NK cell modulation against HNSCC remains unknown. In this study, we investigated whether BME can enhance the NK cell killing activity against HNSCC cells...
May 2, 2017: Cancer Prevention Research
https://www.readbyqxmd.com/read/28465262/non-thermal-plasma-induces-a-stress-response-in-mesothelioma-cells-resulting-in-increased-endocytosis-lysosome-biogenesis-and-autophagy
#6
Lei Shi, Fumiya Ito, Yue Wang, Yasumasa Okazaki, Hiromasa Tanaka, Masaaki Mizuno, Masaru Hori, Tasuku Hirayama, Hideko Nagasawa, Des R Richardson, Shinya Toyokuni
Non-thermal plasma (NTP) is a potential new therapeutic modality for cancer. However, its mechanism of action remains unclear. Herein, we studied the effect of NTP on mesothelioma cells and fibroblasts to understand its anti-proliferative efficacy. Interestingly, NTP demonstrated greater selective anti-proliferative activity against mesothelioma cells relative to fibroblasts than cisplatin, which is used for mesothelioma treatment. The anti-proliferative effect of NTP was enhanced by pre-incubation with the cellular iron donor, ferric ammonium citrate (FAC), and inhibited by iron chelation using desferrioxamine (DFO)...
May 2, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28456985/detection-of-lysosomal-exocytosis-by-surface-exposure-of-lamp1-luminal-epitopes
#7
Norma W Andrews
Elevation in the cytosolic Ca(2+) concentration triggers exocytosis of lysosomes in many cell types. This chapter describes a method to detect lysosomal exocytosis in mammalian cells, which takes advantage of the presence of an abundant glycoprotein, Lamp1, on the membrane of lysosomes. Lamp1 is a transmembrane protein with a large, heavily glycosylated region that faces the lumen of lysosomes. When lysosomes fuse with the plasma membrane, epitopes present on the luminal domain of Lamp1 are exposed on the cell surface...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28448640/mapping-of-the-lassa-virus-lamp1-binding-site-reveals-unique-determinants-not-shared-by-other-old-world-arenaviruses
#8
Hadar Israeli, Hadas Cohen-Dvashi, Anastasiya Shulman, Amir Shimon, Ron Diskin
Cell entry of many enveloped viruses occurs by engagement with cellular receptors, followed by internalization into endocytic compartments and pH-induced membrane fusion. A previously unnoticed step of receptor switching was found to be critical during cell entry of two devastating human pathogens: Ebola and Lassa viruses. Our recent studies revealed the functional role of receptor switching to LAMP1 for triggering membrane fusion by Lassa virus and showed the involvement of conserved histidines in this switching, suggesting that other viruses from this family may also switch to LAMP1...
April 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28445739/autophagy-associated-cytotoxicity-and-cellular-uptake-mechanisms-of-bismuth-nanoparticles-in-human-kidney-cells
#9
Yongming Liu, Jing Zhuang, Xihui Zhang, Cong Yue, Ning Zhu, Liecheng Yang, Yong Wang, Tao Chen, Yangyun Wang, Leshuai W Zhang
Bismuth compounds have been used for treatment of bacterial infection, and recently bismuth nanoparticles (BiNP) were synthesized for imaging and diagnostic purpose, while safety concern of bismuth cannot be ignored. Here, we prepared ultrasmall BiNP and showed an enhanced tumor imaging, but BiNP revealed a differentiated cytotoxicity in human embryonic kidney 293 cells (HEK293) compared to other cell types. For the first time, we found that BiNP can induce autophagy, shown as the increase of monodansylcadaverine fluorescence staining and the amount of LC3II that can be inhibited by 3-MA...
April 23, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28423647/upregulation-of-the-lncrna-meg3-induces-autophagy-to-inhibit-tumorigenesis-and-progression-of-epithelial-ovarian-carcinoma-by-regulating-activity-of-atg3
#10
Yin-Ling Xiu, Kai-Xuan Sun, Xi Chen, Shuo Chen, Yang Zhao, Qing-Guo Guo, Zhi-Hong Zong
Maternally expressed gene 3 (Meg3), a long non-coding RNA, has been reported to be associated with the pathogenesis of multiple malignancies. However, little is known regarding the role of Meg3 in epithelial ovarian cancer (EOC). In this study, we found that the expression of Meg3 was lower in epithelial ovarian carcinoma, and has potential to be considered as a biomarker for ovarian cancer. After transfecting the ovarian cancer cell lines OVCAR3 and A2780 with Meg3, phenotypic changes and autophagy-related molecules were examined...
May 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28413178/synthesized-a%C3%AE-42-caused-intracellular-oxidative-damage-leading-to-cell-death-via-lysosome-rupture
#11
Yuki Oku, Kazuma Murakami, Kazuhiro Irie, Jun Hoseki, Yasuyoshi Sakai
Neuronal cellular accumulation of amyloid beta peptide (Aβ) has been implicated in the pathogenesis of Alzheimer’s disease (AD). Intracellular accumulation of Aβ42, a toxic form of Aβ, was observed as an early event in AD patients. However, its contribution and the cellular mechanism of cell death remained unclear. We herein revealed the mechanism by which Aβ42 incorporated into cells leads to cell death by using chemically synthesized Aβ42 variants. The Aβ42 variant Aβ42 (E22P) which has an increased tendency to oligomerize, accumulated in lysosomes at an earlier stage than wild-type Aβ42, leading to higher ROS production and lysosomal membrane oxidation, and resulting in cell death...
April 12, 2017: Cell Structure and Function
https://www.readbyqxmd.com/read/28390177/role-of-the-lysosomal-membrane-protein-cln3-in-the-regulation-of-cathepsin-d-activity
#12
Jaime Cárcel-Trullols, Attila D Kovács, David A Pearce
Among Neuronal Ceroid Lipofuscinoses (NCLs), which are childhood fatal neurodegenerative disorders, the juvenile onset form (JNCL) is the most common. JNCL is caused by recessive mutations in the CLN3 gene. CLN3 encodes a lysosomal/endosomal transmembrane protein but its precise function is not completely known. We have previously reported that in baby hamster kidney (BHK) cells stably expressing myc-tagged human CLN3 (myc-CLN3), hyperosmotic conditions drastically increased myc-CLN3 mRNA and protein expression...
April 8, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28381826/recombinant-tandem-of-pore-domains-in-a-weakly-inward-rectifying-k-channel-2-twik2-forms-active-lysosomal-channels
#13
Nicole Bobak, Sylvain Feliciangeli, Cheng-Chang Chen, Ismail Ben Soussia, Stefan Bittner, Sophie Pagnotta, Tobias Ruck, Martin Biel, Christian Wahl-Schott, Christian Grimm, Sven G Meuth, Florian Lesage
Recombinant TWIK2 channels produce weak basal background K(+) currents. Current amplitudes depend on the animal species the channels have been isolated from and on the heterologous system used for their re-expression. Here we show that this variability is due to a unique cellular trafficking. We identified three different sequence signals responsible for the preferential expression of TWIK2 in the Lamp1-positive lysosomal compartment. Sequential inactivation of tyrosine-based (Y308ASIP) and di-leucine-like (E266LILL and D282EDDQVDIL) trafficking motifs progressively abolishes the targeting of TWIK2 to lysosomes, and promotes its functional relocation at the plasma membrane...
April 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28365875/effects-of-dha-on-hippocampal-autophagy-and-lysosome-function-after-traumatic-brain-injury
#14
Yan Yin, Eric Li, George Sun, Hong Q Yan, Lesley M Foley, Liwia A Andrzejczuk, Insiya Y Attarwala, T Kevin Hitchens, Kirill Kiselyov, C Edward Dixon, Dandan Sun
Traumatic brain injury (TBI) triggers endoplasmic reticulum (ER) stress and impairs autophagic clearance of damaged organelles and toxic macromolecules. In this study, we investigated the effects of the post-TBI administration of docosahexaenoic acid (DHA) on improving hippocampal autophagy flux and cognitive functions of rats. TBI was induced by cortical contusion injury in Sprague-Dawley rats, which received DHA (16 mg/kg in DMSO, intraperitoneal administration) or vehicle DMSO (1 ml/kg) with an initial dose within 15 min after the injury, followed by a daily dose for 3 or 7 days...
April 1, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28321485/initial-autophagic-protection-switches-to-disruption-of-autophagic-flux-by-lysosomal-instability-during-cadmium-stress-accrual-in-renal-nrk-52e-cells
#15
W-K Lee, S Probst, M P Santoyo-Sánchez, W Al-Hamdani, I Diebels, J-K von Sivers, E Kerek, E J Prenner, F Thévenod
The renal proximal tubule (PT) is the major target of cadmium (Cd(2+)) toxicity where Cd(2+) causes stress and apoptosis. Autophagy is induced by cell stress, e.g., endoplasmic reticulum (ER) stress, and may contribute to cell survival or death. The role of autophagy in Cd(2+)-induced nephrotoxicity remains unsettled due to contradictory results and lack of evidence for autophagic machinery damage by Cd(2+). Cd(2+)-induced autophagy in rat kidney PT cell line NRK-52E and its role in cell death was investigated...
March 20, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28320834/early-intracellular-trafficking-of-granulibacter-bethesdensis-in-human-macrophages
#16
Jessica Chu, Margery G Smelkinson, David W Dorward, Kol A Zarember, John I Gallin
Granulibacter bethesdensis is a Gram-negative bacterium that infects patients with Chronic Granulomatous Disease (CGD), a primary immunodeficiency marked by a defect in NOX2, the phagocyte nicotinamide adenine dinucleotide phosphate oxidase. Previous studies have shown that NOX2 is essential for killing of G. bethesdensis by neutrophils and monocytes and that bacteriostatic activity of monocyte derived macrophages (MDM) requires NOX2 and IFNγ-pretreatment. To determine if G. bethesdensis evades phagolysosomal killing, a host defense pathway intact in both normal and CGD MDM, or occupies a distinct intracellular niche in CGD MDM, we assessed the trafficking patterns of this organism...
March 20, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28296196/sirt6-reduces-macrophage-foam-cell-formation-by-inducing-autophagy-and-cholesterol-efflux-under-ox-ldl-condition
#17
Jiangping He, Guangya Zhang, Qi Pang, Cong Yu, Jie Xiong, Jing Zhu, Fengling Chen
SIRT6 is a pivotal regulator of lipid metabolism. It is also closely connected to cardiovascular diseases, which are the main cause of death in diabetic patients. We observed a decrease in the expression of SIRT6 and key autophagy effectors (ATG5, LC3B, and LAMP1) in ox-LDL-induced foam cells, a special form of lipid-laden macrophages. In these cells, SIRT6 WT but not SIRT6 H133Y overexpression markedly reduced foam cell formation, as shown by Oil Red O staining, while inducing autophagy flux, as determined by both mRFP-GFP-LC3 labeling and transmission electron microscopy...
March 9, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28287144/mir-153-regulates-amelogenesis-by-targeting-endocytotic-and-endosomal-lysosomal-pathways-novel-insight-into-the-origins-of-enamel-pathologies
#18
Kaifeng Yin, Wenting Lin, Jing Guo, Toshihiro Sugiyama, Malcolm L Snead, Joseph G Hacia, Michael L Paine
Amelogenesis imperfecta (AI) is group of inherited disorders resulting in enamel pathologies. The involvement of epigenetic regulation in the pathogenesis of AI is yet to be clarified due to a lack of knowledge about amelogenesis. Our previous genome-wide microRNA and mRNA transcriptome analyses suggest a key role for miR-153 in endosome/lysosome-related pathways during amelogenesis. Here we show that miR-153 is significantly downregulated in maturation ameloblasts compared with secretory ameloblasts. Within ameloblast-like cells, upregulation of miR-153 results in the downregulation of its predicted targets including Cltc, Lamp1, Clcn4 and Slc4a4, and a number of miRNAs implicated in endocytotic pathways...
March 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28278296/robust-growth-of-avirulent-phase-ii-coxiella-burnetii-in-bone-marrow-derived-murine-macrophages
#19
Diane C Cockrell, Carrie M Long, Shelly J Robertson, Jeffrey G Shannon, Heather E Miller, Lara Myers, Charles L Larson, Tregei Starr, Paul A Beare, Robert A Heinzen
Published data show that murine bone marrow-derived macrophages (BMDM) restrict growth of avirulent phase II, but not virulent phase I, Coxiella burnetii. Growth restriction of phase II bacteria is thought to result from potentiated recognition of pathogen-associated molecular patterns, which leads to production of inhibitory effector molecules. Past studies have used conditioned medium from L-929 murine fibroblasts as a source of macrophage-colony stimulating factor (M-CSF) to promote differentiation of bone marrow-derived myeloid precursors into macrophages...
2017: PloS One
https://www.readbyqxmd.com/read/28264968/tim-3-is-a-marker-of-plasmacytoid-dendritic-cell-dysfunction-during-hiv-infection-and-is-associated-with-the-recruitment-of-irf7-and-p85-into-lysosomes-and-with-the-submembrane-displacement-of-tlr9
#20
Jordan Ari Schwartz, Kiera L Clayton, Shariq Mujib, Hongliang Zhang, A K M Nur-Ur Rahman, Jun Liu, Feng Yun Yue, Erika Benko, Colin Kovacs, Mario A Ostrowski
In chronic diseases, such as HIV infection, plasmacytoid dendritic cells (pDCs) are rendered dysfunctional, as measured by their decreased capacity to produce IFN-α. In this study, we identified elevated levels of T cell Ig and mucin-domain containing molecule-3 (Tim-3)-expressing pDCs in the blood of HIV-infected donors. The frequency of Tim-3-expressing pDCs correlated inversely with CD4 T cell counts and positively with HIV viral loads. A lower frequency of pDCs expressing Tim-3 produced IFN-α or TNF-α in response to the TLR7 agonists imiquimod and Sendai virus and to the TLR9 agonist CpG...
March 6, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
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