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endoplasmic reticulum and autophagy

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https://www.readbyqxmd.com/read/29331396/autophagy-in-ischemic-stroke
#1
REVIEW
Pei Wang, Bo-Zong Shao, Zhiqiang Deng, Shi Chen, Zhenyu Yue, Chao-Yu Miao
Autophagy is a self-eating cellular catabolic pathway, through which long-lived proteins, damaged organelles and misfolded proteins are degraded and recycled for the maintenance of cellular homeostasis and normal cellular functions. Autophagy plays an important homeostatic role in the regulation of cell survival. Accumulating evidence shows that autophagy is activated in various cell types in the brain such as neurons, glia cells, and brain microvascular cells upon ischemic stroke. However, the exact role and molecular mechanisms of autophagy process that is implicated in ischemic stroke have yet to be elucidated...
January 10, 2018: Progress in Neurobiology
https://www.readbyqxmd.com/read/29331057/manifestations-and-mechanisms-of-myocardial-lipotoxicity-in-obesity
#2
Arthur C Sletten, Linda R Peterson, Jean E Schaffer
Environmental and socioeconomic changes over the past thirty years have contributed to a dramatic rise in the worldwide prevalence of obesity. Heart disease is among the most serious health risks of obesity, with increases in both atherosclerotic coronary heart disease and heart failure among obese individuals. In this review, we focus on primary myocardial alterations in obesity that include hypertrophic remodeling and diastolic dysfunction. Obesity-associated perturbations in myocardial and systemic lipid metabolism are important contributors to cardiovascular complications of obesity...
January 13, 2018: Journal of Internal Medicine
https://www.readbyqxmd.com/read/29323257/dengue-virus-induced-er-stress-is-required-for-autophagy-activation-viral-replication-and-pathogenesis-both-in-vitro-and-in-vivo
#3
Ying-Ray Lee, Szu-Han Kuo, Ching-Yen Lin, Po-Jung Fu, Yee-Shin Lin, Trai-Ming Yeh, Hsiao-Sheng Liu
Dengue virus (DENV) utilizes the endoplasmic reticulum (ER) for replication and assembling. Accumulation of unfolded proteins in the ER lumen leads to ER stress and unfolded protein response (UPR). Three branches of UPRs temporally modulated DENV infection. Moreover, ER stress can also induce autophagy. DENV infection induces autophagy which plays a promotive role in viral replication has been reported. However, the role of ER stress in DENV-induced autophagy, viral titer, and pathogenesis remain unclear. Here, we reveal that ER stress and its downstream UPRs are indispensable for DENV-induced autophagy in various human cells...
January 11, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29322304/causative-genes-in-amyotrophic-lateral-sclerosis-and-protein-degradation-pathways-a-link-to-neurodegeneration
#4
REVIEW
C Maurel, A Dangoumau, S Marouillat, C Brulard, A Chami, R Hergesheimer, P Corcia, H Blasco, C R Andres, P Vourc'h
Amyotrophic lateral sclerosis (ALS) is a disease caused by the degeneration of motor neurons (MNs) leading to progressive muscle weakness and atrophy. Several molecular pathways have been implicated, such as glutamate-mediated excitotoxicity, defects in cytoskeletal dynamics and axonal transport, disruption of RNA metabolism, and impairments in proteostasis. ALS is associated with protein accumulation in the cytoplasm of cells undergoing neurodegeneration, which is a hallmark of the disease. In this review, we focus on mechanisms of proteostasis, particularly protein degradation, and discuss how they are related to the genetics of ALS...
January 10, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29317574/-role-of-immune-related-gtpase-m1-in-cortical-neurons-autophagy-of-mice-with-sepsis-induced-brain-injury
#5
Qun Huang, Bin Chen, Yafei Li, Xihong Li
To investigate the role of immune-related GTPase M1 (IRGM1) in cortical neurons autophagy in mice with sepsis induced brain injury (SIBI).
 Methods: Sixty wild-type C57BL/6 mice and sixty IRGM1 gene knockout C57BL/6 mice were randomly divided into 4 groups: a sham-operated wild-type (SWT) group, a cecal ligation and puncture (CLP) model wild-type (MWT) group, a sham-operated knockout (SKO) group, and a CLP model knockout (MKO) group. Models of mice with sepsis were established by CLP. Six hours of after CLP, the neurobehavioral scores for mice were recorded...
December 28, 2017: Zhong Nan da Xue Xue Bao. Yi Xue Ban, Journal of Central South University. Medical Sciences
https://www.readbyqxmd.com/read/29317503/er-stress-mobilization-of-death-associated-protein-kinase-1-dependent-xenophagy-counteracts-mitochondria-stress-induced-epithelial-barrier-dysfunction
#6
Fernando Lopes, Åsa V Keita, Alpana Saxena, Jose Luis Reyes, Nicole Mancini, Ala Al Rajabi, Arthur Wang, Cristiane Baggio, Michael Dicay, Rob van Dalen, Younghee Ahn, Matheus Carneiro, Nathan Peters, Jong M Rho, Wallace MacNaughton, Stephan E Girardin, Humberto Jijon, Dana J Philpott, Johan D Söderholm, Derek M McKay
The gut microbiome contributes to inflammatory bowel disease (IBD), in which bacteria can be present within the epithelium. Epithelial barrier function is decreased in IBD, and dysfunctional epithelial mitochondria and endoplasmic reticulum (ER) stress have been individually associated with IBD. We therefore hypothesized that the combination of ER and mitochondrial stresses significantly disrupt epithelial barrier function. Here, we treated human colonic biopsies, epithelial colonoids, and epithelial cells with an uncoupler of oxidative phosphorylation, dinitrophenol (DNP), with or without the ER stressor tunicamycin, and assessed epithelial barrier function by monitoring internalization and translocation of commensal bacteria...
January 9, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29316847/chloroquine-promotes-the-recovery-of-acute-spinal-cord-injury-by-inhibiting-autophagy-associated-inflammation-and-endoplasmic-reticulum-stress
#7
Fenzan Wu, Xiaojie Wei, Yanqing Wu, Xiaoxia Kong, Aiping Hu, Songlin Tong, Yanlong Liu, Fanhua Gong, Ling Xie, Jinjing Zhang, Jian Xiao, Hongyu Zhang
Spinal cord injury (SCI) is a severe nervous system disease that may lead to lifelong disability. Studies have shown that autophagy plays a key role in various diseases; however, the mechanisms regulating crosstalk between autophagy, inflammation and endoplasmic reticulum (ER) stress during SCI recovery remain unclear. This study was designed to investigate the mechanism by which chloroquine (CQ) inhibits autophagy-associated inflammation and ER-stress in rats during their recovery from acute SCI. We evaluated the locomotor function, level of autophagy, and levels of inflammatory cytokines and ER-stress associated proteins and examined the degradation of the key regulator of inflammation I-κBα through autophagy by analyzing the colocalization of I-κBα, p62 and LC3-II...
January 9, 2018: Journal of Neurotrauma
https://www.readbyqxmd.com/read/29314656/mammalian-target-of-rapamycin-inhibition-attenuates-myocardial-ischaemia-reperfusion-injury-in-hypertrophic-heart
#8
Lei-Lei Ma, Xin Ma, Fei-Juan Kong, Jun-Jie Guo, Hong-Tao Shi, Jian-Bing Zhu, Yun-Zeng Zou, Jun-Bo Ge
Pathological cardiac hypertrophy aggravated myocardial infarction and is causally related to autophagy dysfunction and increased oxidative stress. Rapamycin is an inhibitor of serine/threonine kinase mammalian target of rapamycin (mTOR) involved in the regulation of autophagy as well as oxidative/nitrative stress. Here, we demonstrated that rapamycin ameliorates myocardial ischaemia reperfusion injury by rescuing the defective cytoprotective mechanisms in hypertrophic heart. Our results showed that chronic rapamycin treatment markedly reduced the phosphorylated mTOR and ribosomal protein S6 expression, but not Akt in both normal and aortic-banded mice...
January 4, 2018: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29313416/dicot-specific-atg8-interacting-ati3-proteins-interact-with-conserved-ubac2-proteins-and-play-critical-roles-in-plant-stress-responses
#9
Jie Zhou, Zhe Wang, Xiaoting Wang, Xifeng Li, Zhenchao Zhang, Baofang Fan, Cheng Zhu, Zhixiang Chen
Selective macroautophagy/autophagy targets specific cargo by autophagy receptors through interaction with ATG8 (autophagy-related protein 8)/MAP1LC3 (microtubule associated protein 1 light chain 3) for degradation in the vacuole. Here, we report the identification and characterization of 3 related ATG8-interacting proteins (AT1G17780/ATI3A, AT2G16575/ATI3B and AT1G73130/ATI3C) from Arabidopsis. ATI3 proteins contain a WxxL LC3-interacting region (LIR) motif at the C terminus required for interaction with ATG8...
January 9, 2018: Autophagy
https://www.readbyqxmd.com/read/29305265/the-nem1-spo7-protein-phosphatase-complex-is-required-for-efficient-mitophagy-in-yeast
#10
Xueyan Xu, Koji Okamoto
Mitochondria-targeted selective autophagy, termed mitophagy, is an evolutionarily conserved process that contributes to mitochondrial quantity and quality control. Mitophagy requires elaborate membrane biogenesis of autophagosomes surrounding mitochondria, although how this process is regulated remains obscure. We show here that mitophagy is strongly suppressed in yeast cells lacking Nem1 or Spo7, two proteins forming a heterodimeric protein phosphatase complex known to be important for proper shaping of the nucleus and endoplasmic reticulum (ER)...
January 2, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29296828/gene-editing-rescue-of-a-novel-mpl-mutant-associated-with-congenital-amegakaryocytic-thrombocytopenia
#11
Cédric Cleyrat, Romain Girard, Eun H Choi, Éric Jeziorski, Thierry Lavabre-Bertrand, Sylvie Hermouet, Serge Carillo, Bridget S Wilson
Thrombopoietin (Tpo) and its receptor (Mpl) are the principal regulators of early and late thrombopoiesis and hematopoietic stem cell maintenance. Mutations in MPL can drastically impair its function and be a contributing factor in multiple hematologic malignancies, including congenital amegakaryocytic thrombocytopenia (CAMT). CAMT is characterized by severe thrombocytopenia at birth, which progresses to bone marrow failure and pancytopenia. Here we report unique familial cases of CAMT that presented with a previously unreported MPL mutation: T814C (W272R) in the background of the activating MPL G117T (K39N or Baltimore) mutation...
September 26, 2017: Blood Advances
https://www.readbyqxmd.com/read/29284677/munc18c-depletion-attenuates-caerulein-hyperstimulation-induced-pancreatitis
#12
Subhankar Dolai, Tao Liang, Abrahim I Orabi, Li Xie, Douglas Holmyard, Tanveer A Javed, Nestor A Fernandez, Huanli Xie, Mark S Cattral, Debbie C Thurmond, Peter Thorn, Herbert Y Gaisano
Epithelial pancreatic acinar cells perform crucial functions in food digestion, and acinar cell homoeostasis required for secretion of digestive enzymes relies on SNARE-mediated exocytosis. The ubiquitously expressed Sec1/Munc18 protein mammalian uncoordinated-18c (Munc18c) regulates membrane fusion by activating syntaxin-4 (STX-4) to bind cognate SNARE proteins to form a SNARE complex that mediates exocytosis in many cell types. However, in the acinar cell, Munc18c's functions in exocytosis and homeostasis remain inconclusive...
December 28, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29261001/regulation-of-autophagic-proteolysis-by-the-n-recognin-sqstm1-p62-of-the-n-end-rule-pathway
#13
Hyunjoo Cha-Molstad, Su Hyun Lee, Jung Gi Kim, Ki Woon Sung, Joonsung Hwang, Sang Mi Shim, Srinivasrao Ganipisetti, Terry McGuire, Inhee Mook-Jung, Aaron Ciechanover, Xiang-Qun Xie, Bo Yeon Kim, Yong Tae Kwon
In macroautophagy/autophagy, cargoes are collected by specific receptors, such as SQSTM1/p62 (sequestosome 1), and delivered to phagophores for lysosomal degradation. To date, little is known about how cells modulate SQSTM1 activity and autophagosome biogenesis in response to accumulating cargoes. In this study, we show that SQSTM1 is an N-recognin whose ZZ domain binds N-terminal arginine (Nt-Arg) and other N-degrons (Nt-Lys, Nt-His, Nt-Trp, Nt-Phe, and Nt-Tyr) of the N-end rule pathway. The substrates of SQSTM1 include the endoplasmic reticulum (ER)-residing chaperone HSPA5/GRP78/BiP...
December 20, 2017: Autophagy
https://www.readbyqxmd.com/read/29259731/er-driven-membrane-contact-sites-evolutionary-conserved-machineries-for-stress-response-and-autophagy-regulation
#14
REVIEW
Diana Molino, Anna Chiara Nascimbeni, Francesca Giordano, Patrice Codogno, Etienne Morel
Endoplasmic Reticulum (ER), spreading in the whole cell cytoplasm, is a central player in eukaryotic cell homeostasis, from plants to mammals. Beside crucial functions, such as membrane lipids and proteins synthesis and outward transport, the ER is able to connect to virtually every endomembrane compartment by specific tethering molecular machineries, which enables the establishment of membrane-membrane contact sites. ER-mitochondria contact sites have been shown to be involved in autophagosome biogenesis, the main organelle of the autophagy degradation pathway...
2017: Communicative & Integrative Biology
https://www.readbyqxmd.com/read/29250056/reduced-endoplasmic-reticulum-stress-mediated-autophagy-is-required-for-leptin-alleviating-inflammation-in-adipose-tissue
#15
Lu Gan, Zhenjiang Liu, Dan Luo, Qian Ren, Hua Wu, Changxing Li, Chao Sun
Leptin is an adipocyte-derived hormone and maintains adipose function under challenged conditions. Autophagy is also essential to maintain cellular homeostasis and regulate characteristics of adipose tissue. However, the effects of leptin on autophagy of adipocyte remain elusive. Here, we demonstrated endoplasmic reticulum (ER) stress and leptin were correlated with autophagy and inflammation by transcriptome sequencing of adipose tissue. Leptin-mediated inhibition of autophagy was involved in upstream reduction of ER stress proteins such as Chop, GRP78, and Atf4, since blockage of autophagy using pharmacological approach had no effect on tunicamycin-induced ER stress...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29239661/enhancement-of-the-antimycobacterial-activity-of-macrophages-by-ajoene
#16
Ji-Ae Choi, Soo-Na Cho, Yun-Ji Lim, Junghwan Lee, Dam Go, Seon-Hwa Kim, Chang-Hwa Song
Ajoene, a garlic-derived sulfur-containing compound, has broad-spectrum antimicrobial activity. To assess the potential of ajoene for treating tuberculosis (TB), we determined whether it induces the stress response of the endoplasmic reticulum (ER), which plays an important role in TB. We showed that ajoene stimulation induced the production of ER stress sensor molecules and reactive oxygen species (ROS) levels. Ajoene-induced ROS production was dependent on c-Jun N-terminal kinase (JNK) activation. Interestingly, the inhibition of JNK activity and suppression of ROS production reduced ajoene-induced CHOP production in macrophages...
January 1, 2017: Innate Immunity
https://www.readbyqxmd.com/read/29238517/exogenous-h2s-restores-ischemic-post-conditioning-induced-cardioprotection-through-inhibiting-endoplasmic-reticulum-stress-in-the-aged-cardiomyocytes
#17
Weiming Sun, Jinxia Yang, Yuanzhou Zhang, Yuxin Xi, Xin Wen, Di Yuan, Yuehong Wang, Can Wei, Rui Wang, Lingyun Wu, Hongzhu Li, Changqing Xu
Background: A gasotransmitter hydrogen sulfide (H2S) plays an important physiological and pathological role in cardiovascular system. Ischemic post-conditioning (PC) provides cardioprotection in the young hearts but not in the aged hearts. Exogenous H2S restores PC-induced cardioprotection by inhibition of mitochondrial permeability transition pore opening and oxidative stress and increase of autophagy in the aged hearts. However, whether H2S contributes to the recovery of PC-induced cardioprotection via down-regulation of endoplasmic reticulum stress (ERS) in the aged hearts is unclear...
2017: Cell & Bioscience
https://www.readbyqxmd.com/read/29238039/helicobacter-pylori-vaca-induces-autophagic-cell-death-in-gastric-epithelial-cells-via-the-endoplasmic-reticulum-stress-pathway
#18
Pan Zhu, Jun Xue, Zhu-Jun Zhang, Yin-Ping Jia, Ya-Nan Tong, Dan Han, Qian Li, Yang Xiang, Xu-Hu Mao, Bin Tang
The Helicobacter pylori vacuolating cytotoxin (VacA) can promote progressive vacuolation and gastric injury and may be associated with human gastric cancer. Increasing evidence indicates that autophagy is involved in the cell death induced by VacA, but the specific mechanisms need to be further elucidated. We show here that VacA could induce autophagy and increase cell death in human gastric cancer cell lines. Further investigations revealed that inhibition of autophagy could decrease the VacA-induced cell death in AGS cells...
December 13, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/29235250/discovery-and-mechanistic-elucidation-of-a-class-of-pdi-inhibitors-for-the-treatment-of-glioblastoma
#19
Anahita Kyani, Shuzo Tamura, Suhui Yang, Andrea Shergalis, Soma Somanta, Yuting Kuang, Mats Ljungman, Nouri Neamati
Protein disulfide isomerase (PDI) is overexpressed in glioblastoma, the most aggressive form of brain cancer, and folds nascent proteins responsible for the progression and spread of the disease. Herein, we describe a novel, nanomolar PDI inhibitor, pyrimidotriazinedione 35G8, that is toxic in a panel of human glioblastoma cell lines. We performed a medium throughput 20,000-compound screen of a diverse subset of 1,000,000 compounds to identify cytotoxic small molecules. Cytotoxic compounds were screened for PDI inhibition, and, from the screen, 35G8 emerged as the most cytotoxic inhibitor of PDI...
December 12, 2017: ChemMedChem
https://www.readbyqxmd.com/read/29233873/er-homeostasis-and-autophagy
#20
REVIEW
Matthew Smith, Simon Wilkinson
The endoplasmic reticulum (ER) is a key site for lipid biosynthesis and folding of nascent transmembrane and secretory proteins. These processes are maintained by careful homeostatic control of the environment within the ER lumen. Signalling sensors within the ER detect perturbations within the lumen (ER stress) and employ downstream signalling cascades that engage effector mechanisms to restore homeostasis. The most studied signalling mechanism that the ER employs is the unfolded protein response (UPR), which is known to increase a number of effector mechanisms, including autophagy...
December 12, 2017: Essays in Biochemistry
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