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https://www.readbyqxmd.com/read/28526886/fk866-attenuates-acute-hepatic-failure-through-c-jun-n-terminal-kinase-jnk-dependent-autophagy
#1
Enshuang Guo, Renlong Li, Jiankun Yang, Jun Zhang, Anyi Li, Yan Yang, Shenpei Liu, Anding Liu, Xiaojing Jiang
FK866 exhibits a protective effect on D-galactosamine (GaIN)/lipopolysaccharide (LPS) and concanavalin A (ConA)-induced acute liver failure (ALF), but the mechanism by which FK866 affords this benefit has not yet been elucidated. Autophagy has a protective effect on acute liver injury. However, the contribution of autophagy to FK866-conferred hepatoprotection is still unclear. This study aimed to investigate whether FK866 could attenuate GaIN/LPS and ConA-induced ALF through c-jun-N-terminal kinase (JNK)-dependent autophagy...
May 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28523294/autophagy-in-aging-and-disease
#2
Mădălina Fîlfan, Raluca Elena Sandu, Alexandra Daniela Zăvăleanu, Andrei GreşiŢă, Daniela Gabriela Glăvan, Denissa Greta Olaru, Aurel Popa-Wagner
Autophagy is a catabolic degradation system used to destroy and recycle the unnecessary or damaged components of a cell. Autophagy is present at a basal level in all mammals and is regulated by some conditions, such as oxidative stress, starvation or hypoxia. In aged tissues, increased but also decreased expression of autophagy-specific proteins, Beclin 1, LC3, Atg5 and Atg7 has been reported. Likewise, it could be shown that the lifespan of yeast, nematodes and flies is prolonged by pharmacologically stimulated autophagy using exogenous administered spermidine...
2017: Romanian Journal of Morphology and Embryology, Revue Roumaine de Morphologie et Embryologie
https://www.readbyqxmd.com/read/28518135/rack1-depletion-in-the-ribosome-induces-selective-translation-for-non-canonical-autophagy
#3
Hag Dong Kim, EunBin Kong, YongJoong Kim, Jin-Soo Chang, Joon Kim
RACK1, which was first demonstrated as a substrate of PKCβ II, functions as a scaffold protein and associates with the 40S small ribosomal subunit. According to previous reports, ribosomal RACK1 was also suggested to control translation depending on the status in translating ribosome. We here show that RACK1 knockdown induces autophagy independent of upstream canonical factors such as Beclin1, Atg7 and Atg5/12 conjugates. We further report that RACK1 knockdown induces the association of mRNAs of LC3 and Bcl-xL with polysomes, indicating increased translation of these proteins...
May 18, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28513333/atg9a-deficiency-causes-axon-specific-lesions-including-neuronal-circuit-dysgenesis
#4
Junji Yamaguchi, Chigure Suzuki, Tomohisa Nanao, Soichirou Kakuta, Kentarou Ozawa, Isei Tanida, Tatsuya Saitoh, Takehiko Sunabori, Masaaki Komatsu, Keiji Tanaka, Shigeki Aoki, Kenji Sakimura, Yasuo Uchiyama
Conditional knockout mice for Atg9a, specifically in brain tissue, were generated to understand the roles of ATG9A in the neural tissue cells. The mice were born normally, but half of them died within one week, and none lived beyond 4 weeks of age. SQSTM1/p62 and NBR1, receptor proteins for selective autophagy, together with ubiquitin, accumulated in Atg9a-deficient neurosoma at postnatal day 15 (P15), indicating an inhibition of autophagy, whereas these proteins were significantly decreased at P28, as evidenced by immunohistochemistry, electron microscopy and western blot...
May 17, 2017: Autophagy
https://www.readbyqxmd.com/read/28513279/w09-a-novel-autophagy-enhancer-induces-autophagy-dependent-cell-apoptosis-via-activation-of-the-egfr-mediated-ras-raf1-map2k-mapk1-3-pathway
#5
Pinghu Zhang, Zuguo Zheng, Li Ling, Xiaohui Yang, Ni Zhang, Xue Wang, Maozhi Hu, Yu Xia, Yiwen Ma, Haoran Yang, Yunyi Wang, Hongqi Liu
The EGFR (epidermal growth factor receptor) signaling pathway is frequently deregulated in many malignancies. Therefore, targeting the EGFR pathway is regarded as a promising strategy for anticancer drug discovery. Herein, we identified a 2-amino-nicotinonitrile compound (w09) as a novel autophagy enhancer, which potently induced macroautophagy/autophagy and consequent apoptosis in gastric cancer cells. Mechanistic studies revealed that EGFR-mediated activation of the RAS-RAF1-MAP2K-MAPK1/3 signaling pathway played a critical role in w09-induced autophagy and apoptosis of gastric cancer cells...
May 17, 2017: Autophagy
https://www.readbyqxmd.com/read/28512061/genetic-variants-in-autophagy-associated-genes-are-associated-with-dna-damage-levels-in-chinese-population
#6
Zhihua Li, Junyi Xin, Weihong Chen, Jia Liu, Meng Zhu, Congwen Zhao, Jing Yuan, Guangfu Jin, Hongxia Ma, Jiangbo Du, Zhibin Hu, Tangchun Wu, Hongbing Shen, Juncheng Dai, Hao Yu
Autophagy associated genes (ATGs) played an important role in the repair process of DNA damage and decreased autophagy may weaken the repair process and aggravate DNA damage. Based on this, we hypothesized that DNA damage levels might be modified by genetic variants in autophagy associated genes. In order to validate our hypothesis, 307 subjects were recruited from three different cities (Zhuhai, Wuhan and Tianjin) in China. Demographic data, individual 24-h PM2.5 exposure and peripheral blood DNA damage levels were also detected...
May 13, 2017: Gene
https://www.readbyqxmd.com/read/28510366/hmga2-plays-an-important-role-in-cr-vi-induced-autophagy
#7
Fan Yang, Lian Zhao, Dan Mei, Liping Jiang, Chengyan Geng, Qiujuan Li, Xiaofeng Yao, Yong Liu, Ying Kong, Jun Cao
Cr (VI) is mutagenic and carcinogenic, but the mechanism is unclear. In this study, the involvement of high mobility group A2 (HMGA2) in Cr (VI)-induced autophagy was investigated. Cr (VI) treatment induced formation of autophagosomes, increased expression of LC3II, Atg12-Atg5, Atg4, Atg10, HMGA1 and HMGA2 proteins, and decreased the expression of p62 in A549 cells. Silencing of HMGA2 gene by siRNA blocked Cr (VI)-induced formation of autophagosomes, expression of LC3II, Atg12-Atg5, Atg10 and reduction of p62...
May 16, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28509082/atg7-mediated-autophagy-is-involved-in-the-neural-crest-cell-generation-in-chick-embryo
#8
Guang Wang, En-Ni Chen, Chang Liang, Jianxin Liang, Lin-Rui Gao, Manli Chuai, Andrea Münsterberg, Yongping Bao, Liu Cao, Xuesong Yang
Autophagy plays a very important role in numerous physiological and pathological events. However, it still remains unclear whether Atg7-induced autophagy is involved in the regulation of neural crest cell production. In this study, we found the co-location of Atg7 and Pax7(+) neural crest cells in early chick embryo development. Upregulation of Atg7 with unilateral transfection of full-length Atg7 increased Pax7(+) and HNK-1(+) cephalic and trunk neural crest cell numbers compared to either Control-GFP transfection or opposite neural tubes, suggesting that Atg7 over-expression in neural tubes could enhance the production of neural crest cells...
May 16, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28502476/purkinje-cells-are-more-vulnerable-to-the-specific-depletion-of-cathepsin-d-than-to-that-of-atg7
#9
Masato Koike, Masahiro Shibata, Takehiko Sunabori, Junji Yamaguchi, Kenji Sakimura, Masaaki Komatsu, Keiji Tanaka, Yasuo Uchiyama
Neurologic phenotypes of cathepsin D (CTSD)-deficient mice, a murine model of neuronal ceroid lipofuscinoses, indicate the importance of CTSD for the maintenance of metabolism in central nervous system neurons. To further understand the role of CTSD in central nervous system neurons, we generated mice with a CTSD deficiency specifically in the Purkinje cells (PCs) (CTSD(Flox/Flox);GRID2-Cre) and compared their phenotypes with those of PC-selective Atg7-deficient (Atg7(Flox/Flox);GRID2-Cre) mice. In both strains of mice, PCs underwent degeneration, but the CTSD-deficient PCs disappeared more rapidly than their Atg7-deficient counterparts...
May 11, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28500249/maternal-high-fat-diet-induces-metabolic-stress-response-disorders-in-offspring-hypothalamus
#10
Long The Nguyen, Sonia Saad, Yi Tan, Carol Pollock, Hui Chen
Maternal obesity has been shown to increase the risk of obesity and related disorders in the offspring, which has been partially attributed to changes of appetite regulators in the offspring hypothalamus. On the other hand, endoplasmic reticulum (ER) stress and autophagy have been implicated in hypothalamic neuropeptide dysregulation, thus may also play important roles in such transgenerational effect.  In this study, we show that offspring born to HFD-fed dams showed significantly increased body weight and glucose intolerance, adiposity and plasma triglyceride level at weaning...
May 12, 2017: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/28492544/halofuginone-dually-regulates-autophagic-flux-through-nutrient-sensing-pathways-in-colorectal-cancer
#11
Guo-Qing Chen, Rui-Hong Gong, Da-Jian Yang, Ge Zhang, Ai-Ping Lu, Siu-Cheong Yan, Shu-Hai Lin, Zhao-Xiang Bian
Autophagy has a key role in metabolism and impacts on tumorigenesis. Our previous study found that halofuginone (HF) exerts anticancer activity in colorectal cancer (CRC) by downregulating Akt/mTORC1 (mechanistic target of rapamycin complex 1) signaling pathway. But whether and how HF regulates autophagy and metabolism to inhibit cancer growth remains an open question. Here, we unveil that HF activates ULK1 by downregulation of its phosphorylation site at Ser757 through Akt/mTORC1 signaling pathway, resulting in induction of autophagic flux under nutrient-rich condition...
May 11, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28476020/the-role-of-autophagy-in-hepatocellular-carcinoma-friend-or-foe
#12
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...
April 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28475179/mtorc1-independent-autophagy-regulates-receptor-tyrosine-kinase-phosphorylation-in-colorectal-cancer-cells-via-an-mtorc2-mediated-mechanism
#13
Aikaterini Lampada, James O'Prey, Gyorgy Szabadkai, Kevin M Ryan, Daniel Hochhauser, Paolo Salomoni
The intracellular autophagic degradative pathway can have a tumour suppressive or tumour-promoting role depending on the stage of tumour development. Upon starvation or targeting of oncogenic receptor tyrosine kinases (RTKs), autophagy is activated owing to the inhibition of PI3K/AKT/mTORC1 signalling pathway and promotes survival, suggesting that autophagy is a relevant therapeutic target in these settings. However, the role of autophagy in cancer cells where the PI3K/AKT/mTORC1 pathway is constitutively active remains partially understood...
June 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28467355/atg7-regulates-brain-angiogenesis-via-nf-%C3%AE%C2%BAb-dependent-il-6-production
#14
Shi-Fang Zhuang, Dong-Xin Liu, Hui-Jie Wang, Shu-Hong Zhang, Jia-Yi Wei, Wen-Gang Fang, Ke Zhang, Liu Cao, Wei-Dong Zhao, Yu-Hua Chen
The formation of brain vasculature is an essential step during central nervous system development. The molecular mechanism underlying brain angiogenesis remains incompletely understood. The role of Atg7, an autophagy-related protein, in brain angiogenesis was investigated in this study. We found that the microvessel density in mice brains with endothelial-specific knockout of Atg7 (Atg7 EKO) was significantly decreased compared to wild-type control. Consistently, in vitro angiogenesis assays showed that Atg7 knockdown impaired angiogenesis in brain microvascular endothelial cells...
May 3, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28465655/early-amd-like-defects-in-the-rpe-and-retinal-degeneration-in-aged-mice-with-rpe-specific-deletion-of-atg5-or-atg7
#15
Youwen Zhang, Samuel D Cross, James B Stanton, Alan D Marmorstein, Yun Zheng Le, Lihua Y Marmorstein
PURPOSE: To examine the effects of autophagy deficiency induced by RPE-specific deletion of Atg5 or Atg7 in mice as a function of age. METHODS: Conditional knockout mice with a floxed allele of Atg5 or Atg7 were crossed with inducible VMD2-rtTA/Cre transgenic mice. VMD2-directed RPE-specific Cre recombinase expression was induced with doxycycline feeding in the resulting mice. Cre-mediated deletion of floxed Atg5 or Atg7 resulted in RPE-specific inactivation of the Atg5 or Atg7 gene...
2017: Molecular Vision
https://www.readbyqxmd.com/read/28454732/fluvastatin-prevents-lung-adenocarcinoma-bone-metastasis-by-triggering-autophagy
#16
Zuozhang Yang, Zhenyi Su, Judy Park DeWitt, Lin Xie, Yongbin Chen, Xiaojuan Li, Lei Han, Dongqi Li, Junfeng Xia, Ya Zhang, Yihao Yang, Congguo Jin, Jing Zhang, Su Li, Kun Li, Zhiping Zhang, Xin Qu, Zewei He, Yanjin Chen, Yan Shen, Mingyan Ren, Zhongqin Yuan
Bone is one of the most preferred sites of metastasis in lung cancer. Currently, bisphosphonates and denosumab are major agents for controlling tumor-associated skeletal-related events (SREs). However, both bisphosphonates and denosumab significantly increase the risk for jaw osteonecrosis. Statins, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors and the most frequently prescribed cholesterol-lowering agents, have been reported to inhibit tumor progression and induce autophagy in cancer cells...
April 11, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28450279/autophagy-upregulates-pro-renin-receptor-expression-via-reduction-of-p62-sqstm1-and-activation-of-erk1-2-signaling-pathway-in-podocytes
#17
Caixia Li, Helmy M Siragy
Autophagy plays a major role in podocytes health and disease. P62, also known as Sequestosome-1, is a marker for autophagic activity and is required for the formation and degradation of ubiquitnated protein by autophagy. Knockout of p62 enhanced extracellular signal-regulated kinases (ERK1/2) activity. (Pro)renin receptor (PRR) is expressed in podocytes where it contributes to the homeostasis of these cells. The influence of autophagy on (Pro)renin receptor (PRR) expression is unknown. We hypothesized that in podocytes, upregulation of autophagic activity increases PRR expression via reduction of p62 and stimulation of ERK1/2 signaling pathway...
April 27, 2017: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/28441070/the-thr300ala-variant-of-atg16l1-is-associated-with-decreased-risk-of-brain-metastasis-in-patients-with-non-small-cell-lung-cancer
#18
Qian-Xia Li, Xiao Zhou, Ting-Ting Huang, Yang Tang, Bo Liu, Ping Peng, Li Sun, Yi-Hua Wang, Xiang-Lin Yuan
Non-small cell lung cancer (NSCLC) often metastasizes to the brain, but identifying which patients will develop brain metastases (BM) is difficult. Macroautophagy/autophagy is critical for cancer initiation and progression. We hypothesized that genetic variants of autophagy-related genes may affect brain metastases (BM) in NSCLC patients. We genotyped 16 single nucleotide polymorphisms (SNPs) in 7 autophagy-related (ATG) genes (ATG3, ATG5, ATG7, ATG10, ATG12, ATG16L1, and MAP1LC3/LC3) by using DNA from blood samples of 323 NSCLC patients...
April 25, 2017: Autophagy
https://www.readbyqxmd.com/read/28422956/chronic-activation-of-ppar%C3%AE-with-fenofibrate-reduces-autophagic-proteins-in-the-liver-of-mice-independent-of-fgf21
#19
Eunjung Jo, Songpei Li, Qingning Liang, Xinmei Zhang, Hao Wang, Terence P Herbert, Trisha A Jenkins, Aimin Xu, Ji-Ming Ye
Autophagy is a catabolic mechanism to degrade cellular components to maintain cellular energy levels during starvation, a condition where PPARα may be activated. Here we report a reduced autophagic capacity in the liver following chronic activation of PPARα with fenofibrate (FB) in mice. Chronic administration of the PPARα agonist FB substantially reduced the levels of multiple autophagy proteins in the liver (Atg3, Agt4B, Atg5, Atg7 and beclin 1) which were associated with a decrease in the light chain LC3II/LC3I ratio and the accumulation of p62...
2017: PloS One
https://www.readbyqxmd.com/read/28415024/glucocorticoids-differentially-regulate-the-innate-immune-responses-of-tlr4-and-the-cytosolic-dna-sensing-pathway
#20
Jinli Wang, Ruining Wang, Jiahui Yang, Xiaofan Yang, Shengfeng Hu, Hui Wang, Chaoying Zhou, Wenjing Xiong, Qian Wen, Li Ma
Glucocorticoids (GCs) are widely used to treat the chronic inflammatory disorders because of their powerful anti-inflammatory properties; however, their effects on macrophage-mediated immune responses are not completely understood. In the present study, we found that GCs decreased LPS-mediated TBK1 activation and the expression of IFN-β, RANTES and CXCL-10; however, poly(dA:dT)-induced TBK1 activity and cytokine expression were not affected by GCs treatment. Furthermore, GCs decreased the expression of key autophagy-related genes (ATGs), including ATG5, ATG7 and ATG12, and inhibited autophagy in macrophages after LPS stimulation...
April 14, 2017: International Immunopharmacology
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