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https://www.readbyqxmd.com/read/28924380/intracellular-insulin-and-impaired-autophagy-in-a-zebrafish-model-and-a-cell-model-of-type-2-diabetes
#1
Xiang-Hui Meng, Bo Chen, Jing-Pu Zhang
Type 2 diabetes mellitus is characterized by insulin resistance. However, the complete molecular mechanism remains unclear. In this study, zebrafish were fed a long-term high-fat diet to induce type 2 diabetes, which resulted in a higher body weight, body mass index, more lipid vacuoles in liver, increased insulin transcription level in liver, brain and muscle, and high fasting blood glucose in the high-fat diet zebrafish. Oppositely, the transcription levels of insulin substrate-2 and glucose transporter 2 were significantly decreased, indicating insulin signaling pathway and glucose transport impaired in the insulin-targeting tissues...
2017: International Journal of Biological Sciences
https://www.readbyqxmd.com/read/28916785/selective-degradation-of-pu-1-during-autophagy-represses-the-differentiation-and-antitumour-activity-of-th9-cells
#2
Thaiz Rivera Vargas, Zhijian Cai, Yingying Shen, Magalie Dosset, Isis Benoit-Lizon, Tiffany Martin, Aurélie Roussey, Richard A Flavell, François Ghiringhelli, Lionel Apetoh
Autophagy, a catabolic mechanism that involves degradation of cellular components, is essential for cell homeostasis. Although autophagy favours the lineage stability of regulatory T cells, the contribution of autophagy to the differentiation of effector CD4 T cells remains unclear. Here we show that autophagy selectively represses T helper 9 (TH9) cell differentiation. CD4 T cells lacking Atg3 or Atg5 have increased interleukin-9 (IL-9) expression upon differentiation into TH9 cells relative to Atg3- or Atg5-expressing control cells...
September 15, 2017: Nature Communications
https://www.readbyqxmd.com/read/28915706/the-role-of-autophagy-in-hepatocellular-carcinoma-friend-or-foe
#3
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/28899456/clc5-decreases-the-sensitivity-of-multiple-myeloma-cells-to-bortezomib-via-promoting-pro-survival-autophagy
#4
Huimin Zhang, Yuhui Pang, Chuanbao Ma, Jianying Li, Huaquan Wang, Zonghong Shao
Resistance to bortezomib (BZ) is the major problem that largely limits its clinical application in multiple myeloma treatment. In current study, we investigated whether ClC5, a member of the chloride channel family, involved in this process. The results of MTT assay showed that BZ treatment decreased cell viability in three multiple myeloma cell lines (ARH77, U266 and SKO-007), with the IC50 value of 2.83 nM, 4.37 nM and 1.91 nM, respectively. Moreover, BZ increased the conversion of LC3B-I to LC3B-II and expressions of Beclin-1 and ATG5, concomitantly with decreased p62 expression...
September 11, 2017: Oncology Research
https://www.readbyqxmd.com/read/28895586/maresin-1-mitigates-liver-steatosis-in-ob-ob-and-diet-induced-obese-mice
#5
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/28893313/p53-dependent-puma-to-dram-antagonistic-interplay-as-a-key-molecular-switch-in-cell-fate-decision-in-normal-high-glucose-conditions
#6
Alessia Garufi, Giuseppa Pistritto, Silvia Baldari, Gabriele Toietta, Mara Cirone, Gabriella D'Orazi
BACKGROUND: As an important cellular stress sensor phosphoprotein p53 can trigger cell cycle arrest and apoptosis and regulate autophagy. The p53 activity mainly depends on its transactivating function, however, how p53 can select one or another biological outcome is still a matter of profound studies. Our previous findings indicate that switching cancer cells in high glucose (HG) impairs p53 apoptotic function and the transcription of target gene PUMA. METHODS AND RESULTS: Here we report that, in response to drug adriamycin (ADR) in HG, p53 efficiently induced the expression of DRAM (damage-regulated autophagy modulator), a p53 target gene and a stress-induced regulator of autophagy...
September 11, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28893091/lutein-induces-autophagy-via-beclin-1-upregulation-in-iec-6-rat-intestinal-epithelial-cells
#7
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/28888077/microrna-214-3p-a-link-between-autophagy-and-endothelial-cell-dysfunction-in-atherosclerosis
#8
Jing Wang, Wei-Na Wang, Shuang-Bin Xu, Hong Wu, Bing Dai, Dong-Dong Jian, Mei Yang, Yu-Tao Wu, Qiang Feng, Jian-Hua Zhu, Lei Zhang, Li Zhang
AIM: Endothelial cell injury assumes a fundamental part in the pathogenesis of atherosclerosis, and endothelial cell autophagy has protective effects on the development of atherosclerosis, though the underlying molecular regulation mechanism is indistinct. This study is aimed to investigate whether microRNA-214-3p (miR-214-3p) is involved in the endothelial cell autophagy regulation of atherosclerosis. METHODS: We utilized ApoE-/- mice provided with a high-fat diet (HFD) as atherosclerosis model...
September 9, 2017: Acta Physiologica
https://www.readbyqxmd.com/read/28887323/atg5-mediates-a-positive-feedback-loop-between-wnt-signaling-and-autophagy-in-melanoma
#9
Abibatou Ndoye, Anna Budina-Kolomets, Curtis H Kugel, Marie R Webster, Amanpreet Kaur, Reeti Behera, Vito W Rebecca, Ling Li, Patricia A Brafford, Qin Liu, Y N Vashisht Gopal, Michael A Davies, Gordon B Mills, Xiaowei Xu, Hong Wu, Meenhard Herlyn, Michael C Nicastri, Jeffrey D Winkler, Maria S Soengas, Ravi K Amaravadi, Maureen E Murphy, Ashani T Weeraratna
Autophagy mediates resistance to various anticancer agents. In melanoma, resistance to targeted therapy has been linked to expression of Wnt5A, an intrinsic inhibitor of β-catenin, which also promotes invasion. In this study, we assessed the interplay between Wnt5A and autophagy by combining expression studies in human clinical biopsies with functional analyses in cell lines and mouse models. Melanoma cells with high Wnt5A and low β-catenin displayed increased basal autophagy. Genetic blockade of autophagy revealed an unexpected feedback loop whereby knocking down the autophagy factor ATG5 in Wnt5Ahigh cells decreased Wnt5A and increased β-catenin...
September 8, 2017: Cancer Research
https://www.readbyqxmd.com/read/28881678/autophagy-is-required-for-crizotinib-induced-apoptosis-in-met-amplified-gastric-cancer-cells
#10
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/28881659/sirt1-inhibition-promotes-atherosclerosis-through-impaired-autophagy
#11
Xiaofeng Yang, Jingyuan Wei, Yanhao He, Ting Jing, Yanxiang Li, Yunfang Xiao, Bo Wang, Weirong Wang, Jiye Zhang, Rong Lin
SIRT1, a highly conserved NAD(+)-dependent protein deacetylase, plays a pivotal role in the pathogenesis and therapy of atherosclerosis (AS). The aim of this study is to investigate the potential effects of SIRT1 on AS in ApoE(-/-) mice and the underlying mechanisms of autophagy in an ox-LDL-stimulated human monocyte cell line, THP-1. In vivo, the accelerated atherosclerotic progression of mice was established by carotid collar placement; then, mice were treated for 4 weeks with a SIRT1-specific inhibitor, EX-527...
August 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28867212/mir-124-downregulates-bace-1-and-alters-autophagy-in-app-ps1-transgenic-mice
#12
Xiaoxue Du, Xue Huo, Yang Yang, Zhiying Hu, Benson O A Botchway, Yuting Jiang, Marong Fang
One role of BACE 1 (Beta-site amyloid precursor protein cleaving enzyme 1) is to cleave the sequential amyloid precursor protein (APP) into β-Amyloid (Aβ), the accumulation of which is an important participant in the formation of the amyloid plaques and neurofibrillary tangles of Alzheimer's disease (AD). Our previous study showed BACE 1, the potential functional downstream target of miR-124, to be connected to cell death in AD cell models. Recent studies have shown that autophagy is altered in AD, however, as to whether miR-124 is involved in this alteration is not clear...
September 1, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28855439/intrauterine-growth-retardation-promotes-fetal-intestinal-autophagy-in-rats-via-the-mechanistic-target-of-rapamycin-pathway
#13
Chao Wang, Ruiming Zhang, Le Zhou, Jintian He, Qiang Huang, Farman A Siyal, Lili Zhang, Xiang Zhong, Tian Wang
Intrauterine growth retardation (IUGR) impairs fetal intestinal development, and is associated with high perinatal morbidity and mortality. However, the mechanism underlying this intestinal injury is largely unknown. We aimed to investigate this mechanism through analysis of intestinal autophagy and related signaling pathways in a rat model of IUGR. Normal weight (NW) and IUGR fetuses were obtained from primiparous rats via ad libitum food intake and 50% food restriction, respectively. Maternal serum parameters, fetal body weight, organ weights, and fetal blood glucose were determined...
August 31, 2017: Journal of Reproduction and Development
https://www.readbyqxmd.com/read/28855375/shear-stress-induces-non-canonical-autophagic-flux-in-intestinal-epithelial-monolayers
#14
Sun Wook Kim, Jonathan Ehrman, Mok-Ryeon Ahn, Jumpei Kondo, Andrea A Mancheno Lopez, Yun Sik Oh, Hanjune X Kim, Scott W Crawley, James R Goldenring, Matthew J Tyska, Erin C Rericha, Ken S Lau
Flow of fluids through the gut, such as milk from a neonatal diet, generates a shear stress on the unilaminar epithelium lining the lumen.  We report that exposure to physiological levels of fluid shear stress leads to the formation of large vacuoles, containing extracellular content, within polarizing intestinal epithelial cell monolayers.  These observations lead to two questions: how can cells lacking primary cilia transduce shear stress, and what molecular pathways support the formation of vacuoles that can exceed 80% of the cell volume...
August 30, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28844669/polymorphisms-in-autophagy-related-genes-and-the-coal-workers-pneumoconiosis-in-a-chinese-population
#15
Jiali Yuan, Ruhui Han, Ayaaba Esther, Qiuyun Wu, Jingjin Yang, Weiwen Yan, Xiaoming Ji, Yi Liu, Yan Li, Wenxi Yao, Chunhui Ni
Autophagy is an evolutionary conserved intracellular degradation/recycling system that is essential for cellular homeostasis. Dysregulation of this process leads to a number of disorders, including pulmonary fibrosis. However, the genetic association between singe nucleotide polymorphisms of autophagy related genes (ATGs) and the risk of coal workers' pneumoconiosis has not been reported yet. Total of 7 SNPs in ATGs (ATG16, ATG12, ATG5, ATG10) were investigated for their roles in CWP by a case-control study which including 705 CWP patients and 703 control subjects...
October 20, 2017: Gene
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
#16
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/28839236/association-between-genetic-polymorphisms-in-the-autophagy-related-5-gene-promoter-and-the-risk-of-sepsis
#17
Yiming Shao, Feng Chen, Yuhua Chen, Wenying Zhang, Yao Lin, Yujie Cai, Zihan Yin, Shoubao Tao, Qinghui Liao, Jianghao Zhao, Hui Mai, Yanfang He, Junbing He, Lili Cui
Previous studies demonstrated significant roles of autophagy in the pathogenesis of sepsis, but few studies focused on the effect of autophagy-related SNPs on sepsis susceptibility. In this present study, five polymorphisms of ATG5/ATG16L1 were investigated for the possible risk on sepsis in a Chinese Han population. Our results showed that ATG5 expression levels decreased with the severity of sepsis, and rs506027 T > C and rs510432 G > A were associated with sepsis progression and mortality. Moreover, the rs506027 TT and rs510432 GG carriers also exhibited increased expression levels of ATG5...
August 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28838965/blocking-autophagy-enhances-the-pro-apoptotic-effect-of-bufalin-on-human-gastric-cancer-cells-through-endoplasmic-reticulum-stress
#18
Hongyan Zhao, Qinghua Li, Jie Pang, Huilin Jin, Hongwei Li, Xiaoying Yang
Bufalin has been used to treat cancer for several years. However, the molecular mechanisms for its anti-tumor function are not fully understood. This work aimed to investigate the effect of bufalin on the proliferation and apoptosis of human gastric cancer (HGC) cells and the roles of endoplasmic reticulum (ER) stress and autophagy in bufalin induced apoptosis. HGC cell lines, SGC7901 and BGC823 were treated with different concentration of bufalin or 80 nmol/l bufalin for 1, 2, 3 and 4 days. Cell counting kit-8 (CCK-8) assay and direct cell counting method were used to detect proliferation...
August 24, 2017: Biology Open
https://www.readbyqxmd.com/read/28838138/systematic-characterization-of-autophagy-in-gestational-diabetes-mellitus
#19
Lulu Ji, Zhiguo Chen, Yating Xu, Guoping Xiong, Rui Liu, Chao Wu, Hanyang Hu, Lin Wang
Autophagy is a dynamic process that degrades and recycles cellular organelles and proteins to maintain cell homeostasis. Alterations in autophagy occur in various diseases; however, the role of autophagy in gestational diabetes mellitus (GDM) is unknown. In the present study, we characterized the roles and functions of autophagy in GDM patient samples and extravillous trophoblasts cultured with glucose. We found significantly enhanced autophagy in GDM patients. Moreover, high glucose levels enhanced autophagy and cell apoptosis, reducing proliferation and invasion, and these effects were ameliorated through knockdown of ATG5...
August 1, 2017: Endocrinology
https://www.readbyqxmd.com/read/28837383/autophagy-is-required-for-gamete-differentiation-in-the-moss-physcomitrella-patens
#20
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
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