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https://www.readbyqxmd.com/read/29656210/micheliolide-alleviates-hepatic-steatosis-in-db-db-mice-by-inhibiting-inflammation-and-promoting-autophagy-via-ppar-%C3%AE-mediated-nf-%C3%B0%C2%BAb-and-ampk-mtor-signaling
#1
Juan Zhong, Wangqiu Gong, Jing Chen, Yao Qing, Shuyue Wu, Hongbei Li, Chunxi Huang, Yihua Chen, Yuxian Wang, Zhaozhong Xu, Wenting Liu, HongYu Li, Haibo Long
The anti-inflammatory, immunomodulatory, and anticancer effects of micheliolide (MCL) isolated from Michelia champaca were previously reported, but its role and underlying mechanisms in relieving liver steatosis remain unclear. Herein, we investigated the effects of MCL on hepatic steatosis using a db/db mouse model and lipid mixture (LM)-induced AML12 and LO2 cells. The body and liver weights, food consumption, lipid content and liver aminotransferase levels in serum, the lipid content and inflammatory cytokine levels in liver tissue, and the extent of hepatic steatosis in db/db mice were increased compared with those in db/m mice, and these increases were reversed by MCL treatment...
April 12, 2018: International Immunopharmacology
https://www.readbyqxmd.com/read/29649567/nrf2-signaling-and-autophagy-are-complementary-in-protecting-breast-cancer-cells-during-glucose-deprivation
#2
Alyssa Walker, Anju Singh, Ellen Tully, Juhyung Woo, Anne Le, Tu Nguyen, Shyam Biswal, Dipali Sharma, Edward Gabrielson
Autophagy can serve as a mechanism for survival of cells during nutrient deprivation by recycling cellular macromolecules and organelles transiently to provide essential metabolic substrates. However, autophagy itself causes metabolic stress to cells, and other cellular protective mechanisms likely cooperate with autophagy to promote cell survival during nutrient deprivation. In this study, we explored protective mechanisms in breast cancer cells in the setting of glucose deprivation. While breast cancer cells (MCF7 and T47D) survive in glucose-free medium for three days or more, autophagy is induced in this setting...
April 9, 2018: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/29606209/autophagy-contributes-to-regulate-the-ros-levels-and-pcd-progress-in-tmv-infected-tomatoes
#3
Shumin Zhou, Qiang Hong, Yang Li, Qi Li, Mao Wang
Programmed cell death (PCD) and autophagy are both important means for plants to resist pathogen. It is also the main biological reaction of plant immunity. In previous studies, we found that TMV local-infection on tomato leaves not only caused the PCD process in the distal root tissues, but also induced autophagy in root-tip cells. However, the reasons for these biological phenomena are unclear. In order to get deeper insight, the role of a putative inducible factor reactive oxidative species (ROS) was investigated...
April 2018: Plant Science: An International Journal of Experimental Plant Biology
https://www.readbyqxmd.com/read/29603067/secretome-of-differentiated-pc12-cells-restores-the-monocrotophos-induced-damages-in-human-mesenchymal-stem-cells-and-shsy-5y-cells-role-of-autophagy-and-mitochondrial-dynamics
#4
A Srivastava, S Singh, C S Rajpurohit, P Srivastava, A Pandey, D Kumar, V K Khanna, A B Pant
A perturbed cellular homeostasis is a key factor associated with xenobiotic exposure resulting in various ailments. The local cellular microenvironment enriched with secretory components aids in cell-cell communication that restores this homeostasis. Deciphering the underlying mechanism behind this restorative potential of secretome could serve as a possible solution to many health hazards. We, therefore, explored the protective efficacy of the secretome of differentiated PC12 cells with emphasis on induction of autophagy and mitochondrial biogenesis...
March 30, 2018: Neuromolecular Medicine
https://www.readbyqxmd.com/read/29599911/effects-of-carbon-ion-beam-alone-or-in-combination-with-cisplatin-on-malignant-mesothelioma-cells-in-vitro
#5
Sei Sai, Masao Suzuki, Eun Ho Kim, Mitsuhiro Hayashi, Guillaume Vares, Naoyoshi Yamamoto, Tadaaki Miyamoto
Malignant mesothelioma (MM) is extremely aggressive and a typical refractory cancer. In this study we investigated how effective on killing MM cells by carbon ion beam alone or in combination with cisplatin (CDDP) in vitro . Carbon ion beam (at the center of SOBP with 50 keV/µm of average LET) dose-independently suppressed MM cells MESO-1 and H226 cell viability and in combination with CDDP (25 μM) significantly enhanced its action. Relative biological effectiveness (RBE) values at 73 keV/μm and 13 keV/μm portion of carbon ion beam was estimated as 2...
March 13, 2018: Oncotarget
https://www.readbyqxmd.com/read/29594326/dysregulation-of-autophagy-in-rat-liver-with-mitochondrial-dna-depletion-induced-by-the-nucleoside-analogue-zidovudine
#6
Ana Santos-Llamas, Maria J Monte, Jose J G Marin, Maria J Perez
The nucleoside reverse transcriptase inhibitor zidovudine (AZT), used in HIV infection treatment, induces mitochondrial DNA (mtDNA) depletion. A cause-effect relationship between mtDNA status alterations and autophagy has been reported. Both events are common in several liver diseases, including hepatocellular carcinoma. Here, we have studied autophagy activation in rat liver with mtDNA depletion induced by AZT administration in drinking water for 35 days. AZT at a concentration of 1 mg/ml, but not 0.5 mg/ml in the drinking water, decreased mtDNA levels in rat liver and extrahepatic tissues...
March 28, 2018: Archives of Toxicology
https://www.readbyqxmd.com/read/29593730/cd5l-promotes-m2-macrophage-polarization-through-autophagy-mediated-upregulation-of-id3
#7
Lucía Sanjurjo, Gemma Aran, Érica Téllez, Núria Amézaga, Carolina Armengol, Daniel López, Clara Prats, Maria-Rosa Sarrias
CD5L (CD5 molecule-like) is a secreted glycoprotein that controls key mechanisms in inflammatory responses, with involvement in processes such as infection, atherosclerosis, and cancer. In macrophages, CD5L promotes an anti-inflammatory cytokine profile in response to TLR activation. In the present study, we questioned whether CD5L is able to influence human macrophage plasticity, and drive its polarization toward any specific phenotype. We compared CD5L-induced phenotypic and functional changes to those caused by IFN/LPS, IL4, and IL10 in human monocytes...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29593330/ck1%C3%AE-suppresses-lung-tumour-growth-by-stabilizing-pten-and-inducing-autophagy
#8
Junchao Cai, Rong Li, Xiaonan Xu, Le Zhang, Rong Lian, Lishan Fang, Yongbo Huang, Xianming Feng, Ximeng Liu, Xu Li, Xun Zhu, Heng Zhang, Jueheng Wu, Musheng Zeng, Erwei Song, Yukai He, Yuxin Yin, Jun Li, Mengfeng Li
The contribution of autophagy to cancer development remains controversial, largely owing to the fact that autophagy can be tumour suppressive or oncogenic in different biological contexts. Here, we show that in non-small-cell lung cancer (NSCLC), casein kinase 1 alpha 1 (CK1α) suppresses tumour growth by functioning as an autophagy inducer to activate an autophagy-regulating, tumour-suppressive PTEN/AKT/FOXO3a/Atg7 axis. Specifically, CK1α bound the C-terminal tail of PTEN and enhanced both PTEN stability and activity by competitively antagonizing NEDD4-1-induced PTEN polyubiquitination and abrogating PTEN phosphorylation, thereby inhibiting AKT activity and activating FOXO3a-induced transcription of Atg7...
April 2018: Nature Cell Biology
https://www.readbyqxmd.com/read/29587440/7-acetylsinumaximol-b-induces-apoptosis-and-autophagy-in-human-gastric-carcinoma-cells-through-mitochondria-dysfunction-and-activation-of-the-perk-eif2%C3%AE-atf4-chop-signaling-pathway
#9
Tsung-Chang Tsai, Kuei-Hung Lai, Jui-Hsin Su, Yu-Jen Wu, Jyh-Horng Sheu
The 7-Acetylsinumaximol B (7-AB), a bioactive cembranoid, was originally discovered from aquaculture soft coral Sinularia sandensis . The current study investigated the anti-proliferative property of 7-AB towards the NCI-N87 human gastric cancer cell line. An MTT cell proliferative assay was applied to evaluate cell survival, and immunofluorescence staining and western blotting were employed to analyze the effects of 7-AB on autophagy and apoptosis. Our results showed that 7-AB exerted a concentration-dependent anti-proliferative effect on NCI-N87 cells, and fluorescence staining indicated that the effect was due to the apoptosis induced by 7-AB...
March 26, 2018: Marine Drugs
https://www.readbyqxmd.com/read/29587298/the-effect-of-and-mechanism-underlying-autophagy-in-hepatocellular-carcinoma-induced-by-ch12-a-monoclonal-antibody-directed-against-epidermal-growth-factor-receptor-variant-iii
#10
Wen Xu, Fei Song, Biao Wang, Kesang Li, Mi Tian, Min Yu, Xiaorong Pan, Bizhi Shi, Jianwen Liu, Jianren Gu, Zonghai Li, Hua Jiang
BACKGROUND/AIMS: Epidermal growth factor receptor variant III (EGFRvIII), the most frequent EGFR variant, is constitutively activated without binding to EGF and is correlated with a poor prognosis. CH12, a human-mouse chimeric monoclonal antibody, has been developed in our laboratory and selectively binds to overexpressed EGFR and EGFRvIII. A previous study had reported that EGFR could influence autophagic activity, and autophagy is closely related to tumor development and the response to drug therapy...
March 21, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29581784/autophagy-inhibition-stimulates-apoptosis-in-oesophageal-squamous-cell-carcinoma-treated-with-fasudil
#11
Fa-Jun Xie, Qiu-Qing Zheng, Jing Qin, Ling-Ling Zhang, Na Han, Wei-Min Mao
Fasudil has been proven to be a promising chemotherapeutic drug for various malignancies. However, the potential anticancer effects of fasudil in oesophageal squamous cell carcinoma (ESCC) remain to be established. We confirmed the RhoA activity is inhibited by fasudil in ESCC cells. Then measured the effects of fasudil on apoptosis and autophagy in ESCC. Our study showed fasudil could both induce ESCCs apoptosis and autophagy, and when fasudil-induced autophagy was inhibited by knockdown of the essential autophagy genes (Beclin 1 or ATG7), and pharmacologic agent (chloroquine) treatment, both treatments also significantly sensitized ESCC to fasudil-induced apoptosis, reducing cell viability in vitro...
2018: Journal of Cancer
https://www.readbyqxmd.com/read/29580144/natural-dietary-compound-naringin-prevents-azoxymethane-dextran-sodium-sulfate-induced-chronic-colorectal-inflammation-and-carcinogenesis-in-mice
#12
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...
March 26, 2018: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/29574782/rab9-dependent-autophagy-is-required-for-the-igf-iir-triggering-mitophagy-to-eliminate-damaged-mitochondria
#13
Chih-Yang Huang, Wei-Wen Kuo, Tsung-Jung Ho, Shu-Fen Chiang, Pei-Ying Pai, Jing-Ying Lin, Ding-Yu Lin, Chia-Hua Kuo, Chih-Yang Huang
Mitochondria dysfunction is the major characteristic of mitophagy, which is essential in mitochondrial quality control. However, excessive mitophagy contributes to cell death in a number of diseases, including ischemic stroke and hepatotoxicity. Insulin-like growth factor II (IGF-II) and its receptor (IGF-IIR) play vital roles in the development of heart failure during hypertension. We found that IGF-II triggers IGF-IIR receptor activation, causing mitochondria dysfunction, resulting in mitophagy, and cardiomyocyte cell death...
March 25, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29571878/expression-analysis-of-protein-homeostasis-pathways-in-the-peripheral-blood-mononuclear-cells-of-sporadic-amyotrophic-lateral-sclerosis-patients
#14
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/29568391/proline-oxidase-silencing-induces-proline-dependent-pro-survival-pathways-in-mcf-7-cells
#15
Ilona Zareba, Katarzyna Celinska-Janowicz, Arkadiusz Surazynski, Wojciech Miltyk, Jerzy Palka
Proline degradation by proline dehydrogenase/proline oxidase (PRODH/POX) contributes to apoptosis or autophagy. The identification of specific pathway of apoptosis/survival regulation is the aim of this study. We generated knocked-down PRODH/POX MCF-7 breast cancer cells (MCF-7shPRODH/POX ). PRODH/POX silencing did not affect cell viability. However, it contributed to decrease in DNA and collagen biosynthesis, increase in prolidase activity and intracellular proline concentration as well as increase in the expression of iNOS, NF-κB, mTOR, HIF-1α, COX-2, AMPK, Atg7 and Beclin-1 in MCF-7shPRODH/POX cells...
March 2, 2018: Oncotarget
https://www.readbyqxmd.com/read/29561705/hsp90-inhibition-targets-autophagy-and-induces-a-casp9-dependent-resistance-mechanism-in-nsclc
#16
Jie Han, Leslie A Goldstein, Wen Hou, Suman Chatterjee, Timothy F Burns, Hannah Rabinowich
Macroautophagy/autophagy has emerged as a resistance mechanism to anticancer drug treatments that induce metabolic stress. Certain tumors, including a subset of KRAS-mutant NSCLCs have been shown to be addicted to autophagy, and potentially vulnerable to autophagy inhibition. Currently, autophagy inhibition is being tested in the clinic as a therapeutic component for tumors that utilize this degradation process as a drug resistance mechanism. The current study provides evidence that HSP90 (heat shock protein 90) inhibition diminishes the expression of ATG7, thereby impeding the cellular capability of mounting an effective autophagic response in NSCLC cells...
March 21, 2018: Autophagy
https://www.readbyqxmd.com/read/29555730/a-pex1-missense-mutation-improves-peroxisome-function-in-a-subset-of-arabidopsis-pex6-mutants-without-restoring-pex5-recycling
#17
Kim L Gonzalez, Sarah E Ratzel, Kendall H Burks, Charles H Danan, Jeanne M Wages, Bethany K Zolman, Bonnie Bartel
Peroxisomes are eukaryotic organelles critical for plant and human development because they house essential metabolic functions, such as fatty acid β-oxidation. The interacting ATPases PEX1 and PEX6 contribute to peroxisome function by recycling PEX5, a cytosolic receptor needed to import proteins targeted to the peroxisomal matrix. Arabidopsis pex6 mutants exhibit low PEX5 levels and defects in peroxisomal matrix protein import, oil body utilization, peroxisomal metabolism, and seedling growth. These defects are hypothesized to stem from impaired PEX5 retrotranslocation leading to PEX5 polyubiquitination and consequent degradation of PEX5 via the proteasome or of the entire organelle via autophagy...
March 19, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29550918/filamentous-aggregation-of-sequestosome-1-p62-in-brain-neurons-and-neuroepithelial-cells-upon-tyr-cre-mediated-deletion-of-the-autophagy-gene-atg7
#18
Supawadee Sukseree, Lajos László, Florian Gruber, Sophie Bergmann, Marie Sophie Narzt, Ionela Mariana Nagelreiter, Romana Höftberger, Kinga Molnár, Günther Rauter, Thomas Birngruber, Lionel Larue, Gabor G Kovacs, Erwin Tschachler, Leopold Eckhart
Defects in autophagy and the resulting deposition of protein aggregates have been implicated in aging and neurodegenerative diseases. While gene targeting in the mouse has facilitated the characterization of these processes in different types of neurons, potential roles of autophagy and accumulation of protein substrates in neuroepithelial cells have remained elusive. Here we report that Atg7f/f Tyr-Cre mice, in which autophagy-related 7 (Atg7) is conditionally deleted under the control of the tyrosinase promoter, are a model for accumulations of the autophagy adapter and substrate sequestosome-1/p62 in both neuronal and neuroepithelial cells...
March 17, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29546328/hypoxia-inducible-factor-1%C3%AE-dependent-autophagy-plays-a-role-in-glycolysis-switch-in-mouse-granulosa-cells
#19
Jilong Zhou, Chengyu Li, Wang Yao, Alsiddig M A, Lijun Huo, Honglin Liu, Yi-Liang Miao
Autophagy is an essential cellular mechanism that degrades cytoplasmic proteins and organelles to recycle their components. Here we showed that autophagy was essential for the glycolysis switch and energy homeostasis in mouse granulosa cells (MGCs) under hypoxic condition. Our data indicated that hypoxia inducible factor-1α (HIF-1α) could be largely increased in developing follicles and this remarkable upregulation of HIF-1α triggered cell autophagy and glucose uptake. We found that blocking autophagy by Atg7 knockdown and 3-methyladenine (3-MA) treatment affected the glucose metabolism, with increased glycolytic enzyme activity and decreased ATP production...
March 13, 2018: Biology of Reproduction
https://www.readbyqxmd.com/read/29545903/rapamycin-promotes-the-anticancer-action-of-dihydroartemisinin-in-breast-cancer-mda-mb-231-cells-by-regulating-expression-of-atg7-and-dapk
#20
Qiujun Liu, Xianyao Zhou, Chuan Li, Xuemei Zhang, Chang Long Li
There is limited knowledge regarding the influence of autophagy on the anticancer effect of dihydroartemisinin (DHA). The present study aimed to investigate this influence within human breast cancer cells. Changes in cell viability, cell cycle distribution, apoptosis and associated genes were analyzed in MDA-MB-231 cells subjected to DHA following alteration in autophagy levels; the autophagy level was decreased following autophagy-related 7 (Atg7) knockdown or increased using rapamycin. The data indicated that rapamycin had the ability to notably enhance the anticancer effect of DHA on MDA-MB-231 cells...
April 2018: Oncology Letters
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