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https://www.readbyqxmd.com/read/28916263/autophagy-dependent-generation-of-free-fatty-acids-is-critical-for-normal-neutrophil-differentiation
#1
Thomas Riffelmacher, Alexander Clarke, Felix C Richter, Amanda Stranks, Sumeet Pandey, Sara Danielli, Philip Hublitz, Zhanru Yu, Errin Johnson, Tobias Schwerd, James McCullagh, Holm Uhlig, Sten Eirik W Jacobsen, Anna Katharina Simon
Neutrophils are critical and short-lived mediators of innate immunity that require constant replenishment. Their differentiation in the bone marrow requires extensive cytoplasmic and nuclear remodeling, but the processes governing these energy-consuming changes are unknown. While previous studies show that autophagy is required for differentiation of other blood cell lineages, its function during granulopoiesis has remained elusive. Here, we have shown that metabolism and autophagy are developmentally programmed and essential for neutrophil differentiation in vivo...
September 1, 2017: Immunity
https://www.readbyqxmd.com/read/28915706/the-role-of-autophagy-in-hepatocellular-carcinoma-friend-or-foe
#2
REVIEW
Lian Liu, Jia-Zhi Liao, Xing-Xing He, Pei-Yuan Li
Autophagy is an evolutionarily conserved lysosome-dependent catabolic process which degrades cell's components in order to recycle substrates to exert optimally and adapt to tough circumstances. It is a critical cellular homeostatic mechanism with stress resistance, immunity, antiaging, and pro-tumor or anti-tumor effects. Among these, the role of autophagy in cancer is the most eye-catching that is not immutable but dynamic and highly complex. Basal autophagy acts as a tumor suppressor by maintaining genomic stability in normal cells...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28915631/in-vivo-autophagy-and-biogenesis-of-autophagosomes-within-male-haploid-cells-during-spermiogenesis
#3
Ping Yang, Nisar Ahmed, Lingling Wang, Hong Chen, Yasir Waqas, Tengfei Liu, Abdul Haseeb, Nasrullah Bangulzai, Yufei Huang, Qiusheng Chen
Autophagy is a unique catabolic pathway that is linked to several physiological processes. However, its role in the process of spermiogenesis is largely unknown. The aim of the current study was to determine the in vivo role of autophagy and the origin of autophagosome membrane biogenesis within male haploid cells. Our immunohistochemistry results demonstrated that LC3 and ATG7 localization were increased dramatically in round to elongated spermatids (haploid cells) towards the lumen of seminiferous tubules, however, poorly expressed in the early stages of germ cells near the basal membrane...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28912153/comprehensive-genomic-profiling-of-282-pediatric-low-and-high-grade-gliomas-reveals-genomic-drivers-tumor-mutational-burden-and-hypermutation-signatures
#4
Adrienne Johnson, Eric Severson, Laurie Gay, Jo-Anne Vergilio, Julia Elvin, James Suh, Sugganth Daniel, Mandy Covert, Garrett M Frampton, Sigmund Hsu, Glenn J Lesser, Kimberly Stogner-Underwood, Ryan T Mott, Sarah Z Rush, Jennifer J Stanke, Sonika Dahiya, James Sun, Prasanth Reddy, Zachary R Chalmers, Rachel Erlich, Yakov Chudnovsky, David Fabrizio, Alexa B Schrock, Siraj Ali, Vincent Miller, Philip J Stephens, Jeffrey Ross, John R Crawford, Shakti H Ramkissoon
BACKGROUND: Pediatric brain tumors are the leading cause of death for children with cancer in the U.S. Incorporating next-generation sequencing data for both pediatric low-grade (pLGGs) and high-grade gliomas (pHGGs) can inform diagnostic, prognostic, and therapeutic decision-making. MATERIALS AND METHODS: We performed comprehensive genomic profiling on 282 pediatric gliomas (157 pHGGs, 125 pLGGs), sequencing 315 cancer-related genes and calculating the tumor mutational burden (TMB; mutations per megabase [Mb])...
September 14, 2017: Oncologist
https://www.readbyqxmd.com/read/28904095/distinct-roles-for-motor-neuron-autophagy-early-and-late-in-the-sod1-g93a-mouse-model-of-als
#5
Noam D Rudnick, Christopher J Griffey, Paolo Guarnieri, Valeria Gerbino, Xueyong Wang, Jason A Piersaint, Juan Carlos Tapia, Mark M Rich, Tom Maniatis
Mutations in autophagy genes can cause familial and sporadic amyotrophic lateral sclerosis (ALS). However, the role of autophagy in ALS pathogenesis is poorly understood, in part due to the lack of cell type-specific manipulations of this pathway in animal models. Using a mouse model of ALS expressing mutant superoxide dismutase 1 (SOD1(G93A)), we show that motor neurons form large autophagosomes containing ubiquitinated aggregates early in disease progression. To investigate whether this response is protective or detrimental, we generated mice in which the critical autophagy gene Atg7 was specifically disrupted in motor neurons (Atg7 cKO)...
September 13, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28901537/tetrandrine-antagonizes-acute-megakaryoblastic-leukemia-growth-by-forcing-autophagy-mediated-differentiation
#6
Ting Liu, Zhenxing Zhang, Chunjie Yu, Chang Zeng, Xiaoqing Xu, Guixian Wu, Zan Huang, Wenhua Li
BACKGROUND AND PURPOSE: The dismal prognosis of acute megakaryoblastic leukemia (AMKL) urges for development of novel therapeutic methods. Inducing megakaryoblasts to undergo terminal differentiation was recently shown to be effective as a treatment for AMKL. This encouraged us to identify a potent anti-leukemia compound to induce megakaryocyte differentiation. EXPERIMENTAL APPROACH: Expression of CD41 and morphology change were observed in AMKL cells after tetrandrine treatment...
September 13, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28895586/maresin-1-mitigates-liver-steatosis-in-ob-ob-and-diet-induced-obese-mice
#7
L M Laiglesia, S Lorente-Cebrián, L Martínez-Fernández, N Sáinz, P L Prieto-Hontoria, M A Burrell, C M Rodríguez-Ortigosa, J A Martínez, M J Moreno-Aliaga
BACKGROUND/OBJECTIVES: The aim of this study was to characterize the effects of Maresin 1 (MaR1) in obesity-related liver steatosis and the mechanisms involved. METHODS: MaR1 effects on fatty liver disease were tested in ob/ob (2-10 μg/kg i.p., 20 days) and in diet-induced obese (DIO) mice (2 μg/kg, i.p., or 50 μg/kg, oral gavage for 10 days), as well as in cultured hepatocytes. RESULTS: In ob/ob mice, MaR1 reduced liver triglycerides (TG) content, fatty acid synthase (FAS) and stearoyl-CoA desaturase-1 protein expression, while increased acetyl-CoA carboxylase (ACC) phosphorylation and LC3II protein expression, in parallel with a drop in p62 levels...
September 12, 2017: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/28893091/lutein-induces-autophagy-via-beclin-1-upregulation-in-iec-6-rat-intestinal-epithelial-cells
#8
Chi-Jen Chang, Ji-Fan Lin, Chien-Yu Hsiao, Hsun-Hao Chang, Hsin-Ju Li, Hsun-Hsien Chang, Gon-Ann Lee, Chi-Feng Hung
Lutein is a carotenoid with anti-oxidant properties. Autophagy, an evolutionarily conserved catabolic cellular pathway for coping with stress conditions, is responsive to reactive oxygen species (ROS) and degrades damaged organelles. We previously demonstrated that lutein can induce anti-oxidant enzymes to relieve methotrexate-induced ROS stress. We therefore hypothesized that lutein, which activates ROS-scavenging enzymes, can also induce autophagy for cell survival. In this study, we demonstrated that lutein treatment attenuated the reduction in cell viability caused by H2O2...
2017: American Journal of Chinese Medicine
https://www.readbyqxmd.com/read/28881678/autophagy-is-required-for-crizotinib-induced-apoptosis-in-met-amplified-gastric-cancer-cells
#9
Rebecca D Schroeder, Woonyoung Choi, David S Hong, David J McConkey
MET amplification has been clinically credentialed as a therapeutic target in gastric cancer, but the molecular mechanisms underlying sensitivity and resistance to MET inhibitors are still not well understood. Using whole-genome mRNA expression profiling, we identified autophagy as a top molecular pathway that was activated by the MET inhibitor crizotinib in drug-sensitive human gastric cancer cells, and functional studies confirmed that crizotinib increased autophagy levels in the drug-sensitive cells in a concentration-dependent manner...
August 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28878796/autophagy-is-rapidly-induced-by-salt-stress-and-is-required-for-salt-tolerance-in-arabidopsis
#10
Liming Luo, Pingping Zhang, Ruihai Zhu, Jing Fu, Jing Su, Jing Zheng, Ziyue Wang, Dan Wang, Qingqiu Gong
Salinity stress challenges agriculture and food security globally. Upon salt stress, plant growth slows down, nutrients are recycled, osmolytes are produced, and reallocation of Na(+) takes place. Since autophagy is a high-throughput degradation pathway that contributes to nutrient remobilization in plants, we explored the involvement of autophagic flux in salt stress response of Arabidopsis with various approaches. Confocal microscopy of GFP-ATG8a in transgenic Arabidopsis showed that autophagosome formation is induced shortly after salt treatment...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28874882/glucosyltransferase-activity-of-clostridium-difficile-toxin-b-triggers-autophagy-mediated-cell-growth-arrest
#11
Ruina He, Jingyu Peng, Pengfei Yuan, Junjiao Yang, Xiaoji Wu, Yinan Wang, Wensheng Wei
Autophagy is a bulk cell-degradation process that occurs through the lysosomal machinery, and many reports have shown that it participates in microbial pathogenicity. However, the role of autophagy in Clostridium difficile infection (CDI), the leading cause of antibiotics-associated diarrhea, pseudomembranous colitis and even death in severe cases, is not clear. Here we report that the major virulent factor toxin B (TcdB) of Clostridium difficile elicits a strong autophagy response in host cells through its glucosyltransferase activity...
September 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28860495/mir-96-attenuates-status-epilepticus-induced-brain-injury-by-directly-targeting-atg7-and-atg16l1
#12
Jing Gan, Qianyun Cai, Yi Qu, Fengyan Zhao, Chaomin Wan, Rong Luo, Dezhi Mu
Status epilepticus (SE) can cause brain damage and lead to neural dysfunction. Developing novel targets for SE therapy and diagnosis is important and necessary. Previously, we found several differentially expressed microRNAs (miRNAs) in the developing hippocampus following SE, including the autophagy-related miR-96. In the present study, we employed immunofluorescence staining and Western blot analysis to assess the expression of autophagy-related 7 (Atg7) and Atg16L1 and the status of autophagosome formation in the hippocampus of immature rats with SE...
August 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28854420/tetrahydroxystilbene-glycoside-improves-microvascular-endothelial-dysfunction-and-ameliorates-obesity-associated-hypertension-in-obese-zdf-rats-via-inhibition-of-endothelial-autophagy
#13
Qianqian Dong, Wenjuan Xing, Feifei Su, Xiangyan Liang, Fei Tian, Feng Gao, Siwang Wang, Haifeng Zhang
AIMS: Obesity is a major risk for hypertension. Endothelial dysfunction contributes to increased peripheral vascular resistance and subsequent hypertension. Autophagy regulates endothelial function, however, whether autophagy is related to hypertension in obesity remains largely unclear. We wished to ascertain: (i) the role of autophagy in obesity-induced hypertension and the underlying mechanisms; (ii) if tetrahydroxystilbene glycoside (TSG) influences endothelial dysfunction and obesity-associated hypertension...
August 30, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28841353/esrra-estrogen-related-receptor-alpha-is-a-key-coordinator-of-transcriptional-and-post-translational-activation-of-autophagy-to-promote-innate-host-defense
#14
Soo Yeon Kim, Chul-Su Yang, Hye-Mi Lee, Jin Kyung Kim, Yi-Sak Kim, Ye-Ram Kim, Jae-Sung Kim, Tae Sung Kim, Jae-Min Yuk, Catherine Rosa Dufour, Sang-Hee Lee, Jin-Man Kim, Hueng-Sik Choi, Vincent Giguère, Eun-Kyeong Jo
The orphan nuclear receptor ESSRA (estrogen related receptor, alpha) is a key regulator of energy homeostasis and mitochondrial function. Macroautophagy/autophagy, an intracellular degradation process, is a critical innate effector against intracellular microbes. Here, we demonstrate that ESRRA is required for the activation of autophagy to promote innate antimicrobial defense against mycobacterial infection. AMP-activated protein kinase pathway and SIRT1 (sirtuin 1) activation led to induction of ESRRA, which is essential for autophagosome formation, in bone marrow-derived macrophages...
August 25, 2017: Autophagy
https://www.readbyqxmd.com/read/28837383/autophagy-is-required-for-gamete-differentiation-in-the-moss-physcomitrella-patens
#15
Victoria Sanchez Vera, Chandra Shekar Kenchappa, Katarina Landberg, Simon Bressendorff, Stefan Schwarzbach, Tom Martin, John Mundy, Morten Petersen, Mattias Thelander, Eva Sundberg
Autophagy, a major catabolic process in eukaryotes, was initially related to cell tolerance to nutrient depletion. In plants autophagy has also been widely related to tolerance to biotic and abiotic stresses (through the induction or repression of programmed cell death, PCD) as well as to promotion of developmentally regulated PCD, starch degradation or caloric restriction important for life span. Much less is known regarding its role in plant cell differentiation. Here we show that macroautophagy, the autophagy pathway driven by engulfment of cytoplasmic components by autophagosomes and its subsequent degradation in vacuoles, is highly active during germ cell differentiation in the early diverging land plant Physcomitrella patens...
August 24, 2017: Autophagy
https://www.readbyqxmd.com/read/28837152/lysosomotropism-depends-on-glucose-a-chloroquine-resistance-mechanism
#16
Laura E Gallagher, Ohood A Radhi, Mahmud O Abdullah, Anthony G McCluskey, Marie Boyd, Edmond Y W Chan
There has been long-standing interest in targeting pro-survival autophagy as a combinational cancer therapeutic strategy. Clinical trials are in progress testing chloroquine (CQ) or its derivatives in combination with chemo- or radiotherapy for solid and haematological cancers. Although CQ has shown efficacy in preclinical models, its mechanism of action remains equivocal. Here, we tested how effectively CQ sensitises metastatic breast cancer cells to further stress conditions such as ionising irradiation, doxorubicin, PI3K-Akt inhibition and serum withdrawal...
August 24, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28837150/three-dimensional-tumor-cell-growth-stimulates-autophagic-flux-and-recapitulates-chemotherapy-resistance
#17
Corinna Bingel, Emily Koeneke, Johannes Ridinger, Annika Bittmann, Martin Sill, Heike Peterziel, Jagoda K Wrobel, Inga Rettig, Till Milde, Uta Fernekorn, Frank Weise, Andreas Schober, Olaf Witt, Ina Oehme
Current preclinical models in tumor biology are limited in their ability to recapitulate relevant (patho-) physiological processes, including autophagy. Three-dimensional (3D) growth cultures have frequently been proposed to overcome the lack of correlation between two-dimensional (2D) monolayer cell cultures and human tumors in preclinical drug testing. Besides 3D growth, it is also advantageous to simulate shear stress, compound flux and removal of metabolites, e.g., via bioreactor systems, through which culture medium is constantly pumped at a flow rate reflecting physiological conditions...
August 24, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28831172/pioglitazone-enhances-cytosolic-lipolysis-%C3%AE-oxidation-and-autophagy-to-ameliorate-hepatic-steatosis
#18
Pi-Jung Hsiao, Hsin-Ying Clair Chiou, He-Jiun Jiang, Mei-Yueh Lee, Tusty-Jiuan Hsieh, Kung-Kai Kuo
Non-alcoholic fatty liver disease closely contributes to the development of obesity and insulin resistance. Even though pioglitazone has been reported to effectively lessen hepatic steatosis in human studies, its molecular mechanism remains unclear. This study is designed to investigate the regulation of cytosolic lipolysis, β-oxidation and autophagy by pioglitazone in a mice model of high fat diet (HFD) and cell model incubated with palmitic acid. Our results revealed hepatic steatosis was apparently induced by HFD and it was significantly reversed by pioglitazone...
August 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28826228/carbon-monoxide-inhibits-islet-apoptosis-via-induction-of-autophagy
#19
Do-Sung Kim, Lili Song, Jingjing Wang, Hongju Wu, Wenyu Gou, Wanxing Cui, Jae-Sung Kim, Hongjun Wang
AIM: Carbon monoxide (CO) functions as a therapeutic molecule in various disease models because of its anti-inflammatory and anti-apoptotic properties. We investigated the capacity of CO to reduce hypoxia-induced islet cell death and dysfunction in human and mouse models. RESULTS: Culturing islets in CO-saturated medium protected them from hypoxia-induced apoptosis, and preserved β cell function by suppressing expression of pro-apoptotic (Bim, PARP, Cas-3), pro-inflammatory (TNF-α), and ER stress (glucose-regulated protein 94, grp94, CHOP) proteins...
August 21, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28810608/mechanism-of-microrna-21-regulating-il-6-inflammatory-response-and-cell-autophagy-in-intervertebral-disc-degeneration
#20
Hao Lin, Wenzhi Zhang, Tao Zhou, Wansu Li, Ziao Chen, Chaochao Ji, Chao Zhang, Fang He
This study investigated the mechanism of microRNA-21 in regulating IL-6 inflammatory response and cell autophagy in intervertebral disc degeneration. A total of 10 patients with lumbar disc herniation accompanied by nerve root pain (observation group) and 10 patients with lumbar burst fractures (control group) were selected. The nucleus pulposus tissues of the lesion were obtained during operation for cell culture. Real-time quantitative polymerase chain reaction (PCR) was used to detect the expression of microRNA-21...
August 2017: Experimental and Therapeutic Medicine
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