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Joel M J Tan, Nora Mellouk, Suzanne E Osborne, Dustin A Ammendolia, Diana N Dyer, Ren Li, Diede Brunen, Jorik M van Rijn, Ju Huang, Mark A Czuczman, Marija A Cemma, Amy M Won, Christopher M Yip, Ramnik J Xavier, Donna A MacDuff, Fulvio Reggiori, Jayanta Debnath, Tamotsu Yoshimori, Peter K Kim, Gregory D Fairn, Etienne Coyaud, Brian Raught, Aleixo M Muise, Darren E Higgins, John H Brumell
Plasma membrane integrity is essential for the viability of eukaryotic cells. In response to bacterial pore-forming toxins, disrupted regions of the membrane are rapidly repaired. However, the pathways that mediate plasma membrane repair are unclear. Here we show that autophagy-related (ATG) protein ATG16L1 and its binding partners ATG5 and ATG12 are required for plasma membrane repair through a pathway independent of macroautophagy. ATG16L1 is required for lysosome fusion with the plasma membrane and blebbing responses that promote membrane repair...
December 2018: Nature Microbiology
Ferenc Sipos, Anna L Kiss, Miklós Constantinovits, Zsolt Tulassay, Györgyi Műzes
In relation of immunobiology, the consequence of the crosstalk between TLR9-signaling and autophagy is poorly documented in HT29 cancer cells. To assess the TLR9-mediated biologic effects of modified self-DNA sequences on cell kinetics and autophagy response HT29 cells were incubated separately with intact genomic (g), hypermethylated (m), fragmented (f), and hypermethylated/fragmented (m/f) self-DNAs. Cell viability, apoptosis, cell proliferation, colonosphere-formation were determined. Moreover, the relation of TLR9-signaling to autophagy response was assayed by real-time RT-PCR, immunocytochemistry and transmission electron microscopy (TEM)...
November 21, 2018: Pathology Oncology Research: POR
Martha Zakrzewski, Lisa A Simms, Allison Brown, Mark Appleyard, James Irwin, Nicola Waddell, Graham L Radford-Smith
Background and aims: This study aimed to characterise the mucosa-associated microbiota in ileal Crohn's disease (CD) patients and in healthy controls in terms of host genotype and inflammation status. Methods: The mucosa-associated microbiota of intestinal pinch biopsies from 15 ileal CD patients with mild and moderate disease and from 58 healthy controls were analysed by 16S ribosomal sequencing to determine microbial profile differences between (1) IL23R, NOD2 and ATG16L1 genotypes in healthy subjects, (2) ileal CD patients and control subjects, and (3) inflamed and non-inflamed mucosal tissue in CD patients...
November 16, 2018: Journal of Crohn's & Colitis
Jinjin Cai, Karla M Pires, Maroua Ferhat, Bhagirath Chaurasia, Márcio A Buffolo, Rana Smalling, Ashot Sargsyan, Donald L Atkinson, Scott A Summers, Timothy E Graham, Sihem Boudina
Autophagy is a homeostatic cellular process involved in the degradation of long-lived or damaged cellular components. The role of autophagy in adipogenesis is well recognized, but its role in mature adipocyte function is largely unknown. We show that the autophagy proteins Atg3 and Atg16L1 are required for proper mitochondrial function in mature adipocytes. In contrast to previous studies, we found that post-developmental ablation of autophagy causes peripheral insulin resistance independently of diet or adiposity...
November 13, 2018: Cell Reports
Alissa Piekarski-Welsher, Elizabeth Greene, Kentu Lassiter, Byungwhi Caleb Kong, Sami Dridi, Walter Bottje
Background: Feed efficiency (FE) is an important genetic trait in poultry and livestock. Autophagy (self-eating) and proteosomes are cellular processes that remove damaged cell components (e.g., proteins, organelles). As evidence of extensive protein oxidation was observed in Pedigree Male (PedM) broilers exhibiting a low FE (LFE) phenotype compared to a high FE (HFE) phenotype, the main goal of this study was to assess gene and protein expression of the autophagy and proteosome pathways in breast muscle obtained in PedM broilers exhibiting HFE and LFE phenotypes...
2018: Frontiers in Physiology
Shashank Rai, Maryam Arasteh, Matthew Jefferson, Timothy Pearson, Yingxue Wang, Weijiao Zhang, Bertalan Bicsak, Devina Divekar, Penny P Powell, Ronald Nauman, Naiara Beraza, Simon R Carding, Oliver Florey, Ulrike Mayer, Thomas Wileman
Macroautophagy/autophagy delivers damaged proteins and organelles to lysosomes for degradation, and plays important roles in maintaining tissue homeostasis by reducing tissue damage. The translocation of LC3 to the limiting membrane of the phagophore, the precursor to the autophagosome, during autophagy provides a binding site for autophagy cargoes, and facilitates fusion with lysosomes. An autophagy-related pathway called LC3-associated phagocytosis (LAP) targets LC3 to phagosome and endosome membranes during uptake of bacterial and fungal pathogens, and targets LC3 to swollen endosomes containing particulate material or apoptotic cells...
November 7, 2018: Autophagy
Justyna Gil, David Ramsey, Pawel Pawlowski, Elzbieta Szmida, Przemyslaw Leszczynski, Marek Bebenek, Maria M Sasiadek
Despite great progress in research on the subject, the involvement of autophagy in colorectal cancer (CRC) pathogenesis (initiation, progression, metastasis) remains obscure and controversial. Autophagy is a catabolic process, fundamental to cell viability and connected with degradation/recycling of proteins and organelles. In this study, we aimed at investigating the relative expression level of mRNA via Real-Time PCR of 16 chosen genes belonging to Atg8 mammalian orthologs and their conjugation system, comprising GABARAP, GABARAPL1, GABARAPL2, MAP1LC3A, MAP1LC3B, MAP1LC3C, ATG3, ATG7, ATG10, ATG4A, ATG4B, ATG4C, ATG4D, and three genes encoding proteins building the multimeric ATG16L1 complex, namely ATG5, ATG12, and ATG16L1, in 73 colorectal tumors and paired adjacent normal colon mucosa...
October 29, 2018: Medical Oncology
Caihong Wang, Kyle A Bauckman, Adam S B Ross, Jane W Symington, Marianne M Ligon, Gael Scholtes, Akhil Kumar, Hao-Wei Chang, Joy Twentyman, Bisiayo E Fashemi, Ramnik J Xavier, Indira U Mysorekar
50% of Caucasians carry a Thr300Ala variant (T300A) in the protein encoded by the macroautophagy/autophagy gene ATG16L1. Here, we show that the T300A variant confers protection against urinary tract infections (UTIs), the most common infectious disease in women. Using knockin mice carrying the human T300A variant, we show that the variant limits the UTI-causing bacteria, uropathogenic Escherichia coli (UPEC), from establishing persistent intracellular reservoirs, which can seed UTI recurrence. This phenotype is recapitulated in mice lacking Atg16l1 or Atg7 exclusively in the urothelium...
October 18, 2018: Autophagy
Haijin Huang, Jie Tang, Lei Zhang, Yanzhi Bu, Xiaoyu Zhang
Chemotherapy is an important treatment option for gastric cancer (GC); however, chemotherapy usually fails due to drug resistance, particularly multidrug resistance (MDR). In our previous studies, microRNA (miR)‑874 was demonstrated to serve an important role in tumour growth, apoptosis and angiogenesis. In the present study, the precise roles and underlying mechanisms of miR‑874 in MDR were investigated in GC. The overexpression of miR‑874 reversed cancer cell drug resistance in vitro. According to reporter gene and western blot assays, Autophagy‑related 16‑like 1 (ATG16 L1) was identified as a direct target of miR‑874...
October 11, 2018: International Journal of Oncology
Kalaiselvi Palanisamy, Tsung-Hsun Tsai, Tung-Min Yu, Kuo-Ting Sun, Shao-Hua Yu, Feng-Yen Lin, I-Kuan Wang, Chi-Yuan Li
Autophagy, a prosurvival mechanism offers a protective role during acute kidney injury. We show novel findings on the functional role of RNA binding protein, HuR during hypoxia-induced autophagy in renal proximal tubular cells-2 (HK-2). HK-2 cells showed upregulated expressions of HuR and autophagy-related proteins such as autophagy related 7 (ATG7), autophagy related 16 like 1 (ATG16L1), and LC3II under hypoxia. Increased autophagosome formation was visualized as LC3 puncta in hypoxic cells. Further, short hairpin-RNA-mediated loss of HuR function in HK-2 cells significantly decreased ATG7 and ATG16L1 protein expressions...
October 14, 2018: Journal of Cellular Physiology
Guillaume Le Baut, Claire O'Brien, Paul Pavli, Maryline Roy, Philippe Seksik, Xavier Tréton, Stéphane Nancey, Nicolas Barnich, Madeleine Bezault, Claire Auzolle, Dominique Cazals-Hatem, Jérome Viala, Matthieu Allez, Jean-Pierre Hugot, Anne Dumay
Yersinia are common contaminants of food products, but their prevalence in the human gut is poorly documented. Yersinia have been implicated in Crohn's Disease (CD, an inflammatory bowel disease) however their role in CD is controversial. We performed highly sensitive PCR assays of specific sequences for the gyrB gene of Y. aldovae, Y. bercovieri, Y. enterocolitica, Y. intermedia, Y. mollaretii and the inv gene of Y. pseudotuberculosis . We analyzed a total of 470 ileal samples taken from 338 participants (262 CD patients and 76 controls) belonging to three independent cohorts...
2018: Frontiers in Cellular and Infection Microbiology
Ben C King, Klaudia Kulak, Ulrika Krus, Rebecca Rosberg, Ewelina Golec, Katarzyna Wozniak, Maria F Gomez, Enming Zhang, David J O'Connell, Erik Renström, Anna M Blom
We show here that human pancreatic islets highly express C3, which is both secreted and present in the cytosol. Within isolated human islets, C3 expression correlates with type 2 diabetes (T2D) donor status, HbA1c, and inflammation. Islet C3 expression is also upregulated in several rodent diabetes models. C3 interacts with ATG16L1, which is essential for autophagy. Autophagy relieves cellular stresses faced by β cells during T2D and maintains cellular homeostasis. C3 knockout in clonal β cells impaired autophagy and led to increased apoptosis after exposure of cells to palmitic acid and IAPP...
October 1, 2018: Cell Metabolism
Ahmed M Fahmy, Marwa Khabir, Matthieu Blanchet, Patrick Labonté
Hepatitis C virus (HCV) infection is known to induce autophagosome accumulation as observed by the typical punctate cytoplasmic distribution of LC3B-II in infected cells. Previously, we showed that viral RNA-dependent RNA polymerase (NS5B) interacts with ATG5, a major component of the autophagy elongation complex that is involved in the formation of double-membrane vesicles (DMV), and demonstrated that the autophagy elongation complex (ATG5-12/16L1) but not LC3B is required for proper membranous web formation...
2018: PloS One
Matteo Santoni, Francesco Piva, Ugo De Giorgi, Alessandra Mosca, Umberto Basso, Daniele Santini, Sebastiano Buti, Cristian Lolli, Carlo Terrone, Marco Maruzzo, Michele Iuliani, Melissa Bersanelli, Alessandro Conti, Roberta Mazzucchelli, Rodolfo Montironi, Luciano Burattini, Rossana Berardi
BACKGROUND/AIM: Autophagy has been shown to be involved in cancer development and response to cancer therapy. In this study, genotypes of autophagic genes were analyzed to assess their correlation with the risk of clear cell renal cell carcinoma (ccRCC) and the outcome of patients treated with pazopanib for metastatic ccRCC. MATERIALS AND METHODS: Single nucleotide polymorphisms (SNPs)were selected in the following genes: ATG4A (rs7880351), ATG4B (rs6709768), ATG4C (rs2886770, rs6670694, rs6683832), ATG5 (rs9373839, rs3804333, rs490010), ATG16L1 (rs6752107), ATG16L2 (rs10751215) and IRGM (rs10059011)...
October 2018: Anticancer Research
Shay Ben-Shachar, Yael Finezilber, Hofit Elad, Keren Rabinowitz, Idan Goren, Ofer Isakov, Henit Yanai, Iris Dotan
Background: We evaluated the impact of variations in ATG16L1 and NOD2 and genes on serologic responses in patients with inflammatory bowel disease (IBD). Methods: We recruited 308 IBD patients: 130 with Crohn's disease (CD), 67 with ulcerative colitis (UC), 111 with UC and an ileal pouch (UC-pouch), and 74 healthy controls. NOD2 variants (1007fs, G908R, R702W) and the ATG16L1 A300T variant were analyzed. The antiglycan antibodies anti-Saccharomyces cerevisiae (ASCA), antilaminaribioside (ALCA), antichitobioside (ACCA), and antimannobioside carbohydrate (AMCA) were analyzed by enzyme-linked immunosorbent assay...
September 27, 2018: Inflammatory Bowel Diseases
Songül Budak Diler, Fatma Aybuğa
Background: Urological cancers (prostate cancer and bladder cancers) are the most common cancers in Western population and its rate is increasing in the Eastern World. Autophagy has appeared as a fundamental repair mechanism for degrading damaged organelles and proteins. It was clear that autophagy gene polymorphisms are correlated with development of inflammatory bowel disease and it can also be related with prostate cancer (PCa) or bladder cancer (BCa). In this study, we aimed to determine if ATG16L1 (Thr300Ala) polymorphism is associated with an increased risk of developing PCa and BCa and to establish correlations between ATG16L1 genotypes and morphological parameters...
September 26, 2018: Asian Pacific Journal of Cancer Prevention: APJCP
Konrad Aden, Florian Tran, Go Ito, Raheleh Sheibani-Tezerji, Simone Lipinski, Jan W Kuiper, Markus Tschurtschenthaler, Svetlana Saveljeva, Joya Bhattacharyya, Robert Häsler, Kareen Bartsch, Anne Luzius, Marlene Jentzsch, Maren Falk-Paulsen, Stephanie T Stengel, Lina Welz, Robin Schwarzer, Björn Rabe, Winfried Barchet, Stefan Krautwald, Gunther Hartmann, Manolis Pasparakis, Richard S Blumberg, Stefan Schreiber, Arthur Kaser, Philip Rosenstiel
A coding variant of the inflammatory bowel disease (IBD) risk gene ATG16L1 has been associated with defective autophagy and deregulation of endoplasmic reticulum (ER) function. IL-22 is a barrier protective cytokine by inducing regeneration and antimicrobial responses in the intestinal mucosa. We show that ATG16L1 critically orchestrates IL-22 signaling in the intestinal epithelium. IL-22 stimulation physiologically leads to transient ER stress and subsequent activation of STING-dependent type I interferon (IFN-I) signaling, which is augmented in Atg16l1 ΔIEC intestinal organoids...
November 5, 2018: Journal of Experimental Medicine
Huishan Guo, Remy Sadoul, Derrick Gibbings
Autophagy-related-5 (Atg5) and Autophagy-related-16-Like-1 (Atg16L1) canonically participate in autophagy. Recent research demonstrates that apart from this, they also control production of extracellular vesicles called exosomes by regulating acidification of late endosomes. Atg5-mediated exosome production increased migration and metastasis of breast cancer cells suggesting exosomes may perform some functions ascribed to autophagy.
2018: Molecular & Cellular Oncology
He Liu, Zhaoyue He, Peter Bode, Holger Moch, Hans-Uwe Simon
Autophagy is a cellular "self-digestion" process known to be essential for various physiological and pathological pathways, including cancer, where its role appears to be context-dependent. In this work, we aimed to investigate the level of autophagy by evaluating the expression of key autophagy-related proteins (ATGs) in testicular germ cell tumors (TGCT) for which autophagy has been rarely investigated. We decided to use an immunohistochemical (IHC) staining approach employing a tissue microarray (TMA)...
2018: Frontiers in Oncology
Claudio Lera Orsatti, Marcone Lima Sobreira, Valéria Cristina Sandrim, Jorge Nahas-Neto, Fabio Lera Orsatti, Eliana Aguiar Petri Nahas
BACKGROUND: Early identification of asymptomatic postmenopausal women (PW), who are more predisposed to developing cardiovascular disease (CVD), is an important preventive strategy. Autophagy-related 16-like 1 (ATG16L1) is an autophagy gene known to control host immune responses and is associated with a variety of diseases, including CVD. OBJECTIVE: The aim of the study was to associate the ATG16L1 polymorphism variant with subclinical carotid atherosclerosis in asymptomatic PW...
November 2018: Clinical Biochemistry
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