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https://www.readbyqxmd.com/read/27922761/%C3%AE-6%C3%AE-4-integrin-regulates-the-collective-migration-of-epithelial-cells
#1
Zachary T Colburn, Jonathan C R Jones
α6β4 integrin is localized in a unique punctate distribution at the cell-substratum interface along the leading front of single, front-rear polarized, A549 cells. These puncta are interspersed between focal adhesions and lack association with the actin cytoskeleton. Knockdown of β4 integrin in A549 cells inhibits their directed migration, with knockdown cells exhibiting large focal adhesions and reduced actin dynamics. Despite these changes, the speed of knockdown cells is equivalent to controls cells. Interestingly, in such cells, α6 integrin retains its punctate distribution...
December 6, 2016: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/27922130/the-nmda-receptor-glun2c-subunit-controls-cortical-excitatory-inhibitory-balance-neuronal-oscillations-and-cognitive-function
#2
Subhash C Gupta, Aparna Ravikrishnan, Jinxu Liu, Zhihao Mao, Ratnamala Pavuluri, Brandon G Hillman, Pauravi J Gandhi, Dustin J Stairs, Ming Li, Rajesh R Ugale, Daniel T Monaghan, Shashank M Dravid
Despite strong evidence for NMDA receptor (NMDAR) hypofunction as an underlying factor for cognitive disorders, the precise roles of various NMDAR subtypes remains unknown. The GluN2C-containing NMDARs exhibit unique biophysical properties and expression pattern, and lower expression of GluN2C subunit has been reported in postmortem brains from schizophrenia patients. We found that loss of GluN2C subunit leads to a shift in cortical excitatory-inhibitory balance towards greater inhibition. Specifically, pyramidal neurons in the medial prefrontal cortex (mPFC) of GluN2C knockout mice have reduced mEPSC frequency and dendritic spine density and a contrasting higher frequency of mIPSCs...
December 6, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27916883/enhanced-autophagy-in-polycystic-kidneys-of-aqp11-null-mice
#3
Yasuko Tanaka, Mayumi Watari, Tatsuya Saito, Yoshiyuki Morishita, Kenichi Ishibashi
Aquaporin-11 (AQP11) is an intracellular water channel expressed at the endoplasmic reticulum (ER) of the proximal tubule. Its gene disruption in mice leads to intracellular vacuole formation at one week and the subsequent development of polycystic kidneys by three weeks. As the damaged proximal tubular cells with intracellular vacuoles form cysts later, we postulated that autophagy may play a role in the cyst formation and examined autophagy activity before and after cyst development in AQP11(-/-) kidneys...
November 30, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27911875/autophagy-flux-induced-by-ginsenoside-rg3-attenuates-human-prion-protein-mediated-neurotoxicity-and-mitochondrial-dysfunction
#4
Ji-Hong Moon, Ju-Hee Lee, You-Jin Lee, Sang-Youel Park
Mitochondrial quality control is a process by which mitochondria undergo successive rounds of fusion and fission with dynamic exchange of components to segregate functional and damaged elements. Removal of mitochondrion that contains damaged components is accomplished via autophagy. In this study, we investigated whether ginsenoside Rg3, an active ingredient of the herbal medicine ginseng that is used as a tonic and restorative agent, could attenuate prion peptide, PrP (106-126)-induced neurotoxicity and mitochondrial damage...
November 30, 2016: Oncotarget
https://www.readbyqxmd.com/read/27911445/long-term-outcomes-of-punch-punctoplasty-with-kelly-punch-and-review-of-literature
#5
E S Wong, E Y Li, H K Yuen
PurposeTo report long-term outcomes of punch punctoplasty utilizing the Kelly punch and to compare the results with other described methods of punctoplasty in literature.Patients and methodsA retrospective, non-comparative interventional case series of patients who underwent punch punctoplasty at the Hong Kong Eye Hospital over an 8-year period. A standard Kelly Descemet's membrane punch was utilized for punctal enlargement in all cases. Patient records and their operative records were reviewed. Anatomical success was defined by well-patent puncta on follow-up...
December 2, 2016: Eye
https://www.readbyqxmd.com/read/27909101/changes-in-properties-of-auditory-nerve-synapses-following-conductive-hearing-loss
#6
Xiaowen Zhuang, Wei Sun, Matthew A Xu-Friedman
: Auditory activity plays an important role in the development of the auditory system. Decreased activity can result from conductive hearing loss (CHL) associated with otitis media, which may lead to long-term perceptual deficits. The effects of CHL have been mainly studied at later stages of the auditory pathway, but early stages remain less examined. However, changes in early stages could be important, because they would affect how information about sounds is conveyed to higher order areas for further processing and localization...
December 1, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27905509/the-er-stress-regulator-bip-mediates-cadmium-induced-autophagy-and-neuronal-senescence
#7
Tao Wang, Yan Yuan, Hui Zou, Jinlong Yang, Shiwen Zhao, Yonggang Ma, Yi Wang, Jianchun Bian, Xuezhong Liu, Jianhong Gu, Zongping Liu, Jiaqiao Zhu
Autophagy is protective in cadmium (Cd)-induced oxidative damage. Endoplasmic reticulum (ER) stress has been shown to induce autophagy in a process requiring the unfolded protein response signalling pathways. Cd treatment significantly increased senescence in neuronal cells, which was aggravated by 3-MA or silencing of Atg5 and abolished by rapamycin. Cd increased expression of ER stress regulators Bip, chop, eIf2α, and ATF4, and activated autophagy as evidenced by upregulated LC3. Moreover, the ER stress inhibitor mithramycin inhibited the expression of ER stress protein chaperone Bip and blocked autophagic flux...
December 1, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27895479/cationic-pegylated-liposomes-incorporating-an-antimicrobial-peptide-tilapia-hepcidin-2-3-an-adjuvant-of-epirubicin-to-overcome-multidrug-resistance-in-cervical-cancer-cells
#8
Vivian Juang, Hsin-Pin Lee, Anya Maan-Yuh Lin, Yu-Li Lo
Antimicrobial peptides (AMPs) have been recently evaluated as a new generation of adjuvants in cancer chemotherapy. In this study, we designed PEGylated liposomes encapsulating epirubicin as an antineoplastic agent and tilapia hepcidin 2-3, an AMP, as a multidrug resistance (MDR) transporter suppressor and an apoptosis/autophagy modulator in human cervical cancer HeLa cells. Cotreatment of HeLa cells with PEGylated liposomal formulation of epirubicin and hepcidin 2-3 significantly increased the cytotoxicity of epirubicin...
2016: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/27895162/cannabinoid-receptor-interacting-protein-crip-1a-competition-with-%C3%AE-arrestin-for-cb1-receptor-binding-sites
#9
Lawrence C Blume, Theresa Patten, Khalil Eldeeb, Sandra Leone-Kabler, Alexander A Ilyasov, Bradley M Keegan, Jeremy E O'Neal, Caroline E Bass, Roy R Hantgan, W Todd Lowther, Dana E Selley, Allyn C Howlett
Cannabinoid Receptor Interacting Protein1a (CRIP1a) is a CB1 receptor (CB1R) distal C-terminus-associated protein that alters CB1R interactions with G-proteins (Blume et al.,2015; Smith et al.,2015). We tested the hypothesis that CRIP1a is capable of also altering CB1R interactions with β-arrestin proteins that interact with the CB1R at the C-terminal. Co-immunoprecipitation studies indicated that CB1R associates in complexes with either CRIP1a or β-arrestin, but CRIP1a and β-arrestin fail to co-immunoprecipitate with each other...
November 28, 2016: Molecular Pharmacology
https://www.readbyqxmd.com/read/27875278/ratiometric-analysis-of-acridine-orange-staining-in-the-study-of-acidic-organelles-and-autophagy
#10
Marcos Paulo Thomé, Eduardo Cremonese Filippi-Chiela, Emilly Schlee Villodre, Celina Borges Migliavaca, Giovana Ravizzoni Onzi, Karina Bettega Felipe, Guido Lenz
Acridine orange (AO) is a cell permeable green fluorophore that can be protonated and trapped in Acidic Vesicular Organelles (AVOs). Its metachromatic shift to red fluorescence is concentration-dependent and, therefore, AO fluoresces red in AVOs, such as autolysosomes. This makes AO staining a quick, accessible and reliable method to assess the volume of AVOs, which increases upon autophagy induction. Here we describe a ratiometric analysis of autophagy using AO, considering the red-to-green fluorescence intensity ratio (R/GFIR) to quantify flow cytometry and fluorescence microscopy data of AO-stained cells...
November 14, 2016: Journal of Cell Science
https://www.readbyqxmd.com/read/27875067/transiently-expressed-atg16l1-inhibits-autophagosome-biogenesis-and-aberrantly-targets-rab11-positive-recycling-endosomes
#11
Jiehua Li, Zhixia Chen, Michael T Stang, Wentao Gao
The membrane source for autophagosome biogenesis is an unsolved mystery in the study of autophagy. ATG16L1 forms a complex with ATG12-ATG5 (the ATG16L1 complex). The ATG16L1 complex is recruited to autophagic membranes to convert MAP1LC3B-I to MAP1LC3B-II. The ATG16L1 complex dissociates from the phagophore before autophagosome membrane closure. Thus, ATG16L1 can be used as an early event marker for the study of autophagosome biogenesis. We found that among 3 proteins in the ATG16L1 complex, only ATG16L1 formed puncta-like structures when transiently overexpressed...
November 22, 2016: Autophagy
https://www.readbyqxmd.com/read/27865938/pdmp-a-ceramide-analogue-acts-as-an-inhibitor-of-mtorc1-by-inducing-its-translocation-from-lysosome-to-endoplasmic-reticulum
#12
Takashi Ode, Katarzyna A Podyma-Inoue, Kazue Terasawa, Jin-Ichi Inokuchi, Toshihide Kobayashi, Tetsuro Watabe, Yuichi Izumi, Miki Hara-Yokoyama
Mammalian or mechanistic target of rapamycin complex 1 (mTORC1) is a master regulator of cell growth, metabolism, and cell differentiation. Recent studies have revealed that the recruitment of mTORC1 to lysosomes is essential for its activation. The ceramide analogue 1-phenyl-2-decanoylamino-3-morpholino-1-propanol (PDMP), a well known glycosphingolipid synthesis inhibitor, also affects the structures and functions of various organelles, including lysosomes and endoplasmic reticulum (ER). We investigated whether PDMP regulates the mTORC1 activity through its effects on organellar behavior...
November 16, 2016: Experimental Cell Research
https://www.readbyqxmd.com/read/27862631/microglia-show-altered-morphology-and-reduced-arborisation-in-human-brain-during-aging-and-alzheimer-s-disease
#13
Danielle S Davies, Jolande Ma, Thuvarahan Jegathees, And Claire Goldsbury
Changes in microglia function are involved in Alzheimer's disease (AD) for which ageing is the major risk factor. We evaluated microglial cell process morphologies and their grey matter coverage (arborized area) during ageing and in the presence and absence of AD pathology in autopsied human neocortex. Microglial cell processes were reduced in length, showed less branching and reduced arborized area with aging (case range 52-98 yrs). This occurred during normal ageing and without microglia dystrophy or changes in cell density...
November 14, 2016: Brain Pathology
https://www.readbyqxmd.com/read/27861594/vmp1-establishes-er-microdomains-that-regulate-membrane-contact-sites-and-autophagy
#14
Luis-Carlos Tábara, Ricardo Escalante
The endoplasmic reticulum (ER) regulates organelle dynamics through the formation of membrane contact sites (MCS). Here we describe that VMP1, a multispanning ER-resident protein involved in autophagy, is enriched in ER micro-domains that are in close proximity to diverse organelles in HeLa and Cos-7 cells. These VMP1 puncta are highly dynamic, moving in concert with lipid droplets, mitochondria and endosomes. Some of these micro-domains are associated with ER sliding events and also with fission events of mitochondria and endosomes...
2016: PloS One
https://www.readbyqxmd.com/read/27852894/regulation-of-kif15-localization-and-motility-by-the-c-terminus-of-tpx2-and-microtubule-dynamics
#15
Barbara J Mann, Sai K Balchand, Patricia Wadsworth
Mitotic motor proteins generate force to establish and maintain spindle bipolarity but how they are temporally and spatially regulated in vivo is unclear. Prior work demonstrated that the microtubule-associated protein, TPX2, targets Kinesin-5 and Kinesin-12 motors to spindle microtubules. The C-terminal domain of TPX2 regulates the localization and motility of Kinesin-5, Eg5, but if this domain regulates Kinesin-12, Kif15, is not known. We found that the C-terminal domain of TPX2 contributes to the localization of Kif15 to spindle microtubules in cells and suppresses motor walking in vitro Kif15 and Eg5 are partially redundant motors, and overexpressed Kif15 can drive spindle formation in the absence of Eg5 activity...
November 16, 2016: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/27826112/lipopolysaccharide-induced-autophagy-participates-in-the-control-of-pro-inflammatory-cytokine-release-in-grass-carp-head-kidney-leukocytes
#16
Lei Qin, Xinyan Wang, Shengnan Zhang, Shiyu Feng, Licheng Yin, Hong Zhou
Microtubule-associated protein 1 light chain 3B (LC3B) is a known marker of autophagy in mammals. In the present study, we isolated and identified grass carp LC3B (gcLC3B) cDNA and found its inductive expression in response to bacterial infection in vivo. To assess the occurrence of autophagy in immune response, the role of gcLC3B as an autophagy marker in grass carp was characterized. Accordingly, grass carp kidney cells (CIKs) with stable expression of GFP-gcLC3B were established and GFP-gcLC3B puncta were counted under a confocal fluorescence microscope...
December 2016: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/27813694/autophagy-flux-in-ca1-neurons-of-alzheimer-hippocampus-increased-induction-overburdens-failing-lysosomes-to-propel-neuritic-dystrophy
#17
Matteo Bordi, Martin J Berg, Panaiyur S Mohan, Corrinne M Peterhoff, Melissa J Alldred, Shaoli Che, Stephen D Ginsberg, Ralph A Nixon
Defective autophagy contributes to Alzheimer disease (AD) pathogenesis although evidence is conflicting on whether multiple stages are impaired. Here, for the first time, we have comprehensively evaluated the entire autophagic process specifically in CA1 pyramidal neurons of hippocampus from early and late-stage AD subjects and nondemented controls. CA1 neurons aspirated by laser capture microdissection were analyzed using a custom-designed microarray comprising 578 neuropathology- and neuroscience-associated genes...
November 4, 2016: Autophagy
https://www.readbyqxmd.com/read/27810933/nmdars-adapt-to-neurotoxic-hiv-protein-tat-downstream-of-a-glun2a-ubiquitin-ligase-signaling-pathway
#18
Matthew V Green, Stanley A Thayer
: HIV-associated neurocognitive disorder (HAND) affects about half of HIV-infected patients. Infected non-neuronal cells release neurotoxic factors such as the viral protein, transactivator of transcription (Tat), that potentiate NMDAR function. NMDARs regulate synaptic changes observed following exposure to HIV proteins, which may underlie cognitive impairment in HAND patients. Here we used patch-clamp recording to measure NMDAR-mediated currents in rat hippocampal cultures following exposure to Tat...
November 3, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27810405/anti-proliferation-of-breast-cancer-cells-with-itraconazole-hedgehog-pathway-inhibition-induces-apoptosis-and-autophagic-cell-death
#19
Xiaoya Wang, Sanhua Wei, Yong Zhao, Changhong Shi, Peijuan Liu, Caiqin Zhang, Yingfeng Lei, Bo Zhang, Bing Bai, Yong Huang, Hai Zhang
Itraconazole is a common antifungal which may have promise for treating various human cancers. We report that itraconazole was cytotoxic to MCF-7 and SKBR-3 breast cancer cell lines via apoptosis by altering mitochondria membrane potential, reducing BCL-2 expression and elevating caspase-3 activity. Itraconazole also induced autophagic cell death via LC3-II expression upregulation, P62/SQSTM1 degradation, autophagosome formation and increases in autophagic puncta. Itraconazole treatment inhibited hedgehog pathway key molecular expression, such as SHH and Gli1, resulting in promotion of apoptosis and autophagy The anti-proliferation effect of itraconazole-induced apoptosis and autophagy via hedgehog pathway inhibition was confirmed with Gli1 inhibitor GANT61 and SHH siRNA, GANT61 and SHH siRNA synergistically enhanced cytotoxicity induced by itraconazole...
October 31, 2016: Cancer Letters
https://www.readbyqxmd.com/read/27803889/microrna-20a-inhibits-autophagic-process-by-targeting-atg7-and-atg16l1-and-favors-mycobacterial-survival-in-macrophage-cells
#20
Le Guo, Jin Zhao, Yuliang Qu, Runting Yin, Qian Gao, Shuqin Ding, Ying Zhang, Jun Wei, Guangxian Xu
Autophagy plays important roles in the host immune response against mycobacterial infection. Mycobacterium tuberculosis (M. tuberculosis) can live in macrophages owing to its ability to evade attacks by regulating autophagic response. MicroRNAs (miRNAs) are small noncoding, endogenously encoded RNA which plays critical roles in precise regulation of macrophage functions. Whether miRNAs specifically influence the activation of macrophage autophagy during M. tuberculosis infection are largely unknown. In this study, we demonstrate that BCG infection of macrophages resulted in enhanced expression of miRNA-20a, which inhibits autophagic process by targeting ATG7 and ATG16L1 and promotes BCG survival in macrophages...
2016: Frontiers in Cellular and Infection Microbiology
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