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https://www.readbyqxmd.com/read/30083281/autophagy-receptor-optineurin-promotes-autophagosome-formation-by-potentiating-lc3-ii-production-and-phagophore-maturation
#1
Megha Bansal, Shivranjani C Moharir, Ghanshyam Swarup
Autophagy is an essential physiological process that maintains cellular homeostasis by eliminating harmful protein aggregates, damaged organelles and certain pathogens through lysosomal degradation. During autophagy specialized structures, known as autophagosomes are formed that recruit the cargo through autophagy receptors, and deliver it to lysosomes. Optineurin (Optn) is an autophagy receptor that mediates cargo selective autophagy. Recently, we have identified a novel function of Optn that promotes autophagosome formation during non-selective autophagy...
2018: Communicative & Integrative Biology
https://www.readbyqxmd.com/read/30080377/the-unique-cofactor-region-of-zika-virus-ns2b-ns3-protease-facilitates-cleavage-of-key-host-proteins
#2
Maureen E Hill, Anil Kumar, James A Wells, Tom C Hobman, Olivier Julien, Jeanne A Hardy
Zika virus is an emerging mosquito-borne pathogen capable of severely damaging developing fetuses as well as causing neurological abnormalities in adults. The molecular details of how Zika virus causes pathologies that are unique amongst the flavivirus family remain poorly understood and have contributed to the lack of Zika antiviral therapies. To elucidate how Zika virus protease (ZVP) affects host cellular pathways and consequent pathologies, we used unbiased N-terminomics to identify 31 human proteins cleaved by the NS2B-NS3 protease...
August 6, 2018: ACS Chemical Biology
https://www.readbyqxmd.com/read/30046303/the-role-of-autophagy-and-related-micrornas-in-inflammatory-bowel-disease
#3
REVIEW
Shiyuan Wang, Yan Huang, Cili Zhou, Huangan Wu, Jimeng Zhao, Luyi Wu, Min Zhao, Fang Zhang, Huirong Liu
Accumulating evidence demonstrates that microRNA- (miR-) mediated posttranscriptional regulation plays an important role in autophagy in inflammatory bowel disease (IBD), a disease that is difficult to manage clinically because of the associated chronic recurrent nonspecific inflammation. Research indicates that microRNAs regulate autophagy via different pathways, playing an important role in the IBD process and providing a new perspective for IBD research. Related studies have shown that miR-142-3p, miR-320, miR-192, and miR-122 target NOD2 , an IBD-relevant autophagy gene, to modulate autophagy in IBD...
2018: Gastroenterology Research and Practice
https://www.readbyqxmd.com/read/30036188/sodium-fluoride-induces-splenocyte-autophagy-via-the-mammalian-targets-of-rapamycin-mtor-signaling-pathway-in-growing-mice
#4
Ping Kuang, Huidan Deng, Huan Liu, Hengmin Cui, Jing Fang, Zhicai Zuo, Junliang Deng, Yinglun Li, Xun Wang, Ling Zhao
Fluoride is known to impair organism's development and function via adverse effects, and autophagy plays a regulation role in human or animal health and disease. At present, there are no reports focused on fluoride-induced autophagy in the animal and human spleen. The objective of this study was to investigate sodium fluoride (NaF)-induced splenocyte autophagy and the potential mechanism via regulation of p-mTOR in growing mice by using the methods of transmission electron microscopy (TEM), immunohistochemistry (IHC), quantitative real-time polymerase chain reaction (qRT-PCR) and western blot...
July 22, 2018: Aging
https://www.readbyqxmd.com/read/30030553/reduced-intestinal-epithelial-mitochondrial-function-enhances-in-vitro-interleukin-8-production-in-response-to-commensal-escherichia-coli
#5
Alpana Saxena, Fernando Lopes, Derek M McKay
Uncoupling of oxidative phosphorylation in epithelial mitochondria results in decreased epithelial barrier function as characterized by increased internalization of non-invasive Escherichia coli and their translocation across the epithelium. We hypothesized that the increased burden of intracellular commensal bacteria would activate the enterocyte, with the potential to promote inflammation. Treatment of human colon-derived epithelial cell lines in vitro with dinitrophenol (DNP) and commensal E. coli (strains F18, HB101) provoked increased production of interleukin (IL-8), which was not observed with conditioned medium from the bacteria, lipopolysaccharide or inert beads...
July 20, 2018: Inflammation Research: Official Journal of the European Histamine Research Society ... [et Al.]
https://www.readbyqxmd.com/read/29996716/tfeb-dependent-induction-of-thermogenesis-by-the-hepatocyte-slc2a-inhibitor-trehalose
#6
Yiming Zhang, Cassandra B Higgins, Allyson L Mayer, Indira U Mysorekar, Babak B Razani, Mark J Graham, Paul W Hruz, Brian J DeBosch
The macroautophagy/autophagy-inducing disaccharide, trehalose, has been proposed to be a promising therapeutic agent against neurodegenerative and cardiometabolic diseases. We recently showed that trehalose attenuates hepatic steatosis in part by blocking hepatocyte glucose transport to induce hepatocyte autophagic flux. However, although every major demonstration of trehalose action invokes activating autophagic flux as its primary function, the mechanism of action of trehalose in whole-body energy metabolism remains poorly defined...
July 12, 2018: Autophagy
https://www.readbyqxmd.com/read/29965781/rab26-dependent-autophagy-protects-adherens-junctional-integrity-in-acute-lung-injury
#7
Weijie Dong, Binfeng He, Hang Qian, Qian Liu, Dong Wang, Jin Li, Zhenghua Wei, Zi Wang, Zhi Xu, Guangyu Wu, Guisheng Qian, Guansong Wang
Microvascular barrier dysfunction is the central pathophysiological feature of acute lung injury (ALI). RAB26 is a newly identified small GTPase involved in the regulation of endothelial cell (EC) permeability. However, the mechanism behind this protection has not been clearly elucidated. Here we found that RAB26 promoted the integrity of adherens junctions (AJs) in a macroautophagy/autophagy-dependent manner in ALI. RAB26 is frequently downregulated in mouse lungs after LPS treatment. Mice lacking Rab26 exhibited phosphorylated SRC expression and increased CDH5/VE-cadherin phosphorylation, leading to AJ destruction...
July 26, 2018: Autophagy
https://www.readbyqxmd.com/read/29960072/among-autophagy-genes-atg16l1-but-not-irgm-is-associated-with-crohn-s-disease-in-iranians
#8
Ladan Teimoori-Toolabi, Sanaz Samadpoor, Amirhosein Mehrtash, Mahdis Ghadir, Homayoun Vahedi
BACKGROUND: The prevalence of inflammatory bowel diseases is uprising in countries like Iran. Genetic predisposing elements play prominent role in the pathogenesis of Crohn's disease. In this study we studied the role of autophagy genes like IRGM (Immunity related GTPase M) and ATG16L1 (Autophagy related 16 like 1) in the pathogenesis of Crohn's Disease in Iranian patients. METHODS: One hundred thirty-eight patients and 99 normal controls were recruited in this study...
June 27, 2018: Gene
https://www.readbyqxmd.com/read/29940791/phagophores-evolve-from-recycling-endosomes
#9
Claudia Puri, Mariella Vicinanza, David C Rubinsztein
The membrane origins of autophagosomes have been a key unresolved question in the field. The earliest morphologically recognizable structure in the macroautophagy/autophagy itinerary is the double-membraned cup-shaped phagophore. Newly formed phosphatidylinositol 3-phosphate (PtdIns3P) on the membranes destined to become phagophores recruits WIPI2, which, in turn, binds ATG16L1 to define the sites of autophagosome formation. Here we review our recent study showing that membrane recruitment of WIPI2 requires coincident detection of PtdIns3P and RAB11A, a protein that marks recycling endosomes...
July 23, 2018: Autophagy
https://www.readbyqxmd.com/read/29926669/-changes-in-expression-of-autophagy-related-factors-during-acute-contusion-repair-of-skeletal-muscle
#10
Ao Luo, Cheng-Lin Tang, Si-Qin Huang, Dan-Dan Zhao, An-Ning Zhang, Quan-Hu Guo, Rui-Qi Gao, Jing Cao
OBJECTIVES: To explore the possible biological mechanism of skeletal muscle contusion repair through researching the changes in expression of autophagy-related genes and proteins in SD rats with acute skeletal muscle contusion. METHODS: Six rats were randomly selected as the control group from 30 male SD rats, acute skeletal muscle contusion model were established in the remaining 24 rats with self-made hitter, then the model rats were randomly divided into 4 groups (3 d, 5 d, 7 d, 14 d groups, n =6)...
April 8, 2018: Chinese Journal of Applied Physiology
https://www.readbyqxmd.com/read/29916896/mir-29a-inhibited-intestinal-epithelial-cells-autophagy-partly-by-decreasing-atg9a-in-ulcerative-colitis
#11
Yan Xu, Junwen Yang, Fujun Li, Guanghui Lian, Miao Ouyang
Ulcerative colitis (UC), with high morbidity has become one of the fastest-growing severe illnesses in the world. Although MiR-29a is highly expressed in the tissues of UC patients, the mechanism of miR-29a involved in the specific pathogenesis of UC is not known. In this study, a GFP-light chain 3 (LC3) immunofluorescence assay was used to observe the formation of the autophagic spot; qRT-PCR and western blotting analyses were carried out to detect the expression of autophagy-related proteins, including BECN1, Autophagy-related gene (ATG)5, ATG16L, and transcription factor EB...
August 2018: Anti-cancer Drugs
https://www.readbyqxmd.com/read/29899362/attenuation-of-autophagy-impacts-on-muscle-fibre-development-starvation-induced-stress-and-fibre-regeneration-following-acute-injury
#12
Andrea Paolini, Saleh Omairi, Robert Mitchell, Danielle Vaughan, Antonios Matsakas, Sakthivel Vaiyapuri, Thomas Ricketts, David C Rubinsztein, Ketan Patel
Autophagy has been implicated as a major factor in the development of a number of diseases of skeletal muscle. However, its role in skeletal muscle homeostasis is still evolving. We examined skeletal muscle architecture in a mouse model, Atg16L1, where autophagy is attenuated but importantly still present. We show that muscle fibres from Atg16L1 mice were smaller than wild-type counterparts, proving a role for this process in the growth of these cells. We show that mild attenuation of autophagy results in accelerated muscle loss during the initial phase of acute starvation...
June 13, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29893034/the-microbiome-of-translocated-bacterial-populations-in-patients-with-and-without-inflammatory-bowel-disease
#13
Christopher John Kiely, Paul Pavli, Claire Louise O'Brien
BACKGROUND: Using culture-based methods, bacterial translocation from the gut to draining mesenteric lymph nodes (LNs) is seen in 5% of normal controls and up to 33% of patients with IBD. Many bacteria can't be cultured so these methods are unable to capture the full spectrum of bacteria present. AIMS: To detect viable bacteria in LNs of patients with IBD and non-IBD controls using bacterial RNA as a surrogate for viability and to compare them with the same patient's gut microbiome...
June 11, 2018: Internal Medicine Journal
https://www.readbyqxmd.com/read/29872435/ship1-deficiency-in-inflammatory-bowel-disease-is-associated-with-severe-crohn-s-disease-and-peripheral-t-cell-reduction
#14
Sandra Fernandes, Neetu Srivastava, Raki Sudan, Frank A Middleton, Amandeep K Shergill, James C Ryan, William G Kerr
In our previous study, we observed a severe reduction in the Src homology 2-containing-inositol-phosphatase-1 (SHIP1) protein in a subpopulation of subjects from a small adult Crohn's Disease (CD) cohort. This pilot study had been undertaken since we had previously demonstrated that engineered deficiency of SHIP1 in mice results in a spontaneous and severe CD-like ileitis. Here, we extend our analysis of SHIP1 expression in peripheral blood mononuclear cells in a second much larger adult Inflammatory Bowel Disease (IBD) cohort, comprised of both CD and Ulcerative Colitis patients, to assess contribution of SHIP1 to the pathogenesis of human IBD...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29799774/epithelial-autophagy-controls-chronic-colitis-by-reducing-tnf-induced-apoptosis
#15
Johanna Pott, Kevin J Maloy
Genome-wide association studies (GWAS) linking polymorphisms in ATG16L1 with susceptibility to inflammatory bowel disease (IBD) have prompted mucosal immunologists to investigate the functional roles of macroautophagy/autophagy in different cell types in the gut. Here we present a recent study that addressed 2 key questions: in which cell type is autophagy deficiency most detrimental during chronic colitis and what is the functional role of autophagy in those cells? We report that autophagy in intestinal epithelial cells (IECs) acts to limit intestinal inflammation by protecting them from TNF-induced apoptosis and we discuss the potential implications for IBD treatment...
May 25, 2018: Autophagy
https://www.readbyqxmd.com/read/29746835/complement-c3-drives-autophagy-dependent-restriction-of-cyto-invasive-bacteria
#16
Matthew T Sorbara, Elisabeth G Foerster, Jessica Tsalikis, Mena Abdel-Nour, Joseph Mangiapane, Imogen Sirluck-Schroeder, Ivan Tattoli, Rob van Dalen, David E Isenman, John R Rohde, Stephen E Girardin, Dana J Philpott
In physiological settings, the complement protein C3 is deposited on all bacteria, including invasive pathogens. However, because experimental host-bacteria systems typically use decomplemented serum to avoid the lytic action of complement, the impact of C3 coating on epithelial cell responses to invasive bacteria remains unexplored. Here, we demonstrate that following invasion, intracellular C3-positive Listeria monocytogenes is targeted by autophagy through a direct C3/ATG16L1 interaction, resulting in autophagy-dependent bacterial growth restriction...
May 9, 2018: Cell Host & Microbe
https://www.readbyqxmd.com/read/29580144/natural-dietary-compound-naringin-prevents-azoxymethane-dextran-sodium-sulfate-induced-chronic-colorectal-inflammation-and-carcinogenesis-in-mice
#17
Yu-Sheng Zhang, Feng Wang, Shu-Xiang Cui, Xian-Jun Qu
Naringin, a natural occurring flavonoid compound, enriches in citrus fruits. We aimed to evaluate the inhibitory effect of naringin on colitis and chronic inflammation-driven carcinogenesis. Male C57BL/6 mice were exposed to AOM/DSS to induce colorectal inflammation and carcinogenesis. Naringin by oral administration prevented AOM/DSS-induced ulcerative colitis and carcinogenesis without significant side effects. Naringin attenuated the severity of colitis and colorectal adenomas through inhibiting myeloid-derived suppressor cells (MDSCs), pro-inflammatory mediators GM-CSF/M-CSF, IL-6 and TNF-α and the NF-κB/IL-6/STAT3 cascades in colorectal tissues...
August 3, 2018: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/29571878/expression-analysis-of-protein-homeostasis-pathways-in-the-peripheral-blood-mononuclear-cells-of-sporadic-amyotrophic-lateral-sclerosis-patients
#18
Abhishek Vats, Mandaville Gourie-Devi, Kavita Ahuja, Ankkita Sharma, Saima Wajid, Nirmal Kumar Ganguly, Vibha Taneja
Misfolded protein aggregates are the hallmark of Amyotrophic Lateral Sclerosis (ALS) which suggests involvement of protein homeostasis pathways in etiology of ALS. However, status of protein homeostasis in peripheral blood of ALS is not well established. We analyzed expression levels of key genes of proteostasis pathways in peripheral blood mononuclear cells (PBMCs) of sporadic ALS (sALS) patients and healthy controls. Increased protein carbonylation was observed in patients reflecting oxidative damage in PBMCs...
April 15, 2018: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/29487628/low-serum-zinc-levels-predict-presence-of-depression-symptoms-but-not-overall-disease-outcome-regardless-of-atg16l1-genotype-in-crohn-s-disease-patients
#19
Thomas Greuter, Yannick Franc, Matthias Kaelin, Alain M Schoepfer, Philipp Schreiner, Jonas Zeitz, Michael Scharl, Benjamin Misselwitz, Alex Straumann, Stephan R Vavricka, Gerhard Rogler, Roland von Känel, Luc Biedermann
Background: Zinc deficiency (ZD) in Crohn's disease (CD) is considered a frequent finding and may exacerbate CD activity. ZD is associated with depression in non-CD patients. We aimed to assess the prevalence of ZD in CD patients in clinical remission, its association with mood disturbances and to analyze a potential impact on future disease course. Methods: Zinc levels from CD patients in clinical remission at baseline and an uncomplicated disease course within the next 3 years ( n = 47) were compared with those from patients developing complications ( n = 50)...
2018: Therapeutic Advances in Gastroenterology
https://www.readbyqxmd.com/read/29472524/pu-1-microrna-142-3p-targets-atg5-atg16l1-to-inactivate-autophagy-and-sensitize-hepatocellular-carcinoma-cells-to-sorafenib
#20
Kai Zhang, Jing Chen, Hao Zhou, Ying Chen, Yingru Zhi, Bei Zhang, Longbang Chen, Xiaoyuan Chu, Rui Wang, Chunni Zhang
Sorafenib is currently the only systemic agent approved for treatment of advanced hepatocellular carcinoma (HCC). However, intrinsic and acquired resistance to sorafenib remains a great challenge with respect to improving the prognoses of patients with HCC. The cyto-protective functions of autophagy have been suggested as a potential mechanism by which chemoresistance or targeted drug resistance occurs in tumour cells. In the present study, miR-142-3p was identified as a novel autophagy-regulating microRNA (miRNA) that plays a vital role in sorafenib resistance in HCC cells...
February 22, 2018: Cell Death & Disease
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