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https://www.readbyqxmd.com/read/27909723/inhibition-of-jnk-suppresses-autophagy-and-attenuates-insulin-resistance-in-a-rat-model-of-nonalcoholic-fatty-liver-disease
#1
Hua Yan, Yanqiong Gao, Ying Zhang
Nonalcoholic fatty liver disease (NAFLD) is a common chronic liver disease, the pathological process of which is complex. Activation of the c‑Jun N‑terminal kinase (JNK) signaling pathway is associated with the mechanism underlying obesity-induced insulin resistance. Furthermore, the JNK signaling pathway and dysfunctional autophagy serve important roles in hepatic lipid metabolism. However, the exact role of JNK in autophagy and obesity‑induced insulin resistance is not fully understood. Therefore, the present study aimed to investigate the underlying mechanisms by which the JNK signaling pathway regulates autophagy and insulin resistance in fatty liver...
November 24, 2016: Molecular Medicine Reports
https://www.readbyqxmd.com/read/27905509/the-er-stress-regulator-bip-mediates-cadmium-induced-autophagy-and-neuronal-senescence
#2
Tao Wang, Yan Yuan, Hui Zou, Jinlong Yang, Shiwen Zhao, Yonggang Ma, Yi Wang, Jianchun Bian, Xuezhong Liu, Jianhong Gu, Zongping Liu, Jiaqiao Zhu
Autophagy is protective in cadmium (Cd)-induced oxidative damage. Endoplasmic reticulum (ER) stress has been shown to induce autophagy in a process requiring the unfolded protein response signalling pathways. Cd treatment significantly increased senescence in neuronal cells, which was aggravated by 3-MA or silencing of Atg5 and abolished by rapamycin. Cd increased expression of ER stress regulators Bip, chop, eIf2α, and ATF4, and activated autophagy as evidenced by upregulated LC3. Moreover, the ER stress inhibitor mithramycin inhibited the expression of ER stress protein chaperone Bip and blocked autophagic flux...
December 1, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27904994/rapamycin-protects-sepsis-induced-cognitive-impairment-in-mouse-hippocampus-by-enhancing-autophagy
#3
Wenyu Liu, Jia'nan Guo, Jie Mu, Linyu Tian, Dong Zhou
The purpose of this study is to test the hypothesis that the mammalian target of rapamycin (mTOR) signaling pathway might mediate neuroprotection in a mouse model of septic encephalopathy and also to identify the role of autophagy. Mice were subjected to cecal ligation and puncture (CLP) or a sham operation, and all 50 mice were randomly assigned to five groups: sham, CLP+ saline, CLP+ rapamycin (1, 5, 10 mg/kg) groups. Two weeks after the operation, Morris water maze was conducted for behavioral test; Nissl staining was used for observing glia infiltration; immunohistochemical staining and biochemical measures in hippocampi were performed to detect mTOR targets and autophagy indicators...
December 1, 2016: Cellular and Molecular Neurobiology
https://www.readbyqxmd.com/read/27902874/spodoptera-litura-autophagy-related-protein-1-interacts-with-autophagy-related-protein-5-and-enhances-its-degradation
#4
N Zhang, Y Yang, H Lu, Y Xiang, X Huang, R Hu, Z Chen, W Yuan, R Peng, J Peng, H Ai, K Liu
It is known that the autophagy-related protein 1 (ATG1) plays critical roles in the regulation of autophagy in mammals and yeast, whereas the function of ATG1 in lepidopteran insects is not well elucidated. Here Spodoptera litura ATG1 (SlATG1) and its interactions with other ATG proteins were characterized. Alternative splicing of SlAtg1 produced at least four transcript variants. Over-expression and RNA interference knockdown of SlAtg1 demonstrated that SlATG1 enhanced autophagy. SlATG1A-Green fluorescent protein (GFP) tagged localized in the cytoplasm and formed some punctuate dots, which were colocalized with red fluorescent protein mCherry tagged Spodoptera exigua ATG5 (SeATG5)...
November 30, 2016: Insect Molecular Biology
https://www.readbyqxmd.com/read/27902742/chloroquine-sensitizes-nasopharyngeal-carcinoma-cells-but-not-nasoepithelial-cells-to-irradiation-by-blocking-autophagy
#5
Anna Makowska, Michael Eble, Kirsten Prescher, Mareike Hoß, Udo Kontny
BACKGROUND: Treatment of nasopharyngeal carcinoma requires the application of high dosages of radiation, leading to severe long-term complications in the majority of patients. Sensitizing tumor cells to radiation could be a means to increase the therapeutic window of radiation. Nasopharyngeal carcinoma cells display alterations in autophagy and blockade of autophagy has been shown to sensitize them against chemotherapy. METHODS: We investigated the effect of chloroquine, a known inhibitor of autophagy, on sensitization against radiation-induced apoptosis in a panel of five nasopharyngeal carcinoma cell lines and a SV40-transformed nasoepithelial cell line...
2016: PloS One
https://www.readbyqxmd.com/read/27899249/ginsenoside-20-s-rg3-induced-autophagy-to-inhibit-migration-and-invasion-of-ovarian-cancer
#6
Xia Zheng, Wei Chen, Huilian Hou, Jie Li, Huijin Li, Xiaomin Sun, Le Zhao, Xu Li
BACKGROUND: Autophagy maintains cellular homeostasis through engulfing cytoplasmic proteins and organelles, and plays an important role in cancer initiation and progression. Ginsenoside 20(S)-Rg3, an active ingredient of Panax ginseng, exerts anti-cancer functions in various cancers. However, its molecular mechanisms, including its effect on autophagy, are not fully elucidated in tumor models. METHODS: Ovarian cancer cell line SKOV3 was treated by various concentrations of 20(S)-Rg3...
November 26, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27896021/lithocholic-acid-induces-endoplasmic-reticulum-stress-autophagy-and-mitochondrial-dysfunction-in-human-prostate-cancer-cells
#7
Ahmed A Gafar, Hossam M Draz, Alexander A Goldberg, Mohamed A Bashandy, Sayed Bakry, Mahmoud A Khalifa, Walid AbuShair, Vladimir I Titorenko, J Thomas Sanderson
Lithocholic acid (LCA) is a secondary bile acid that is selectively toxic to human neuroblastoma, breast and prostate cancer cells, whilst sparing normal cells. We previously reported that LCA inhibited cell viability and proliferation and induced apoptosis and necrosis of androgen-dependent LNCaP and androgen-independent PC-3 human prostate cancer cells. In the present study, we investigated the roles of endoplasmic reticulum (ER) stress, autophagy and mitochondrial dysfunction in the toxicity of LCA in PC-3 and autophagy deficient, androgen-independent DU-145 cells...
2016: PeerJ
https://www.readbyqxmd.com/read/27895725/ehhm-a-novel-phenolic-natural-product-from-livistona-chinensis-induces-autophagy-related-apoptosis-in-hepatocellular-carcinoma-cells
#8
Xinsheng Cheng, Feng Zhong, Kun He, Shibo Sun, Hongbo Chen, Jie Zhou
Hepatocellular carcinoma (HCC) ranks the second cause of cancer-associated mortality worldwide. In the present study, the effects and mechanisms of a new phenolic natural product E-[6'-(5'-hydroxypentyl)tricosyl]-4-hydroxy-3-methoxycinnamate (EHHM) isolated from Livistona chinensis on the growth of HCC cells were investigated. It was observed that EHHM treatment significantly suppressed cell proliferation and colony formation, and induced cell apoptosis via a mitochondria-dependent caspase pathway in HepG2 cells in a time- and dose-dependent manner...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27881580/disruption-of-autophagic-degradation-with-roc-325-antagonizes-renal-cell-carcinoma-pathogenesis
#9
Jennifer S Carew, Claudia M Espitia, Weiguo Zhao, Yingchun Han, Valeria Visconte, James G Phillips, Steffan T Nawrocki
PURPOSE: Although autophagy plays important roles in malignant pathogenesis and drug resistance, there are few clinical agents that disrupt this pathway and the potential therapeutic benefit of autophagy inhibition remains undetermined. We used medicinal chemistry approaches to generate a series of novel agents that inhibit autophagic degradation. EXPERIMENTAL DESIGN: ROC-325 was selected as a lead compound for further evaluation. Comprehensive in vitro and in vivo studies were conducted to evaluate the selectivity, tolerability, and efficacy of ROC-325 in preclinical models of renal cell carcinoma (RCC) with HCQ serving as a comparator...
November 23, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27880899/lc3c-contributes-to-vpu-mediated-antagonism-of-bst2-tetherin-restriction-on-hiv-1-release-through-a-non-canonical-autophagy-pathway
#10
Ursula Madjo, Olivier Leymarie, Stéphane Frémont, Aurelia Kuster, Mélanie Nehlich, Sarah Gallois-Montbrun, Katy Janvier, Clarisse Berlioz-Torrent
BST2 (bone marrow stromal antigen 2)/tetherin is a restriction factor of enveloped viruses, which blocks the release of viral particles. HIV-1 encodes proteins that antagonize this innate barrier, including the accessory protein Vpu. Here, we investigate whether the autophagy pathway and/or ATG proteins are hijacked by HIV-1 Vpu to circumvent BST2 restriction of viral release. We report that BST2 and Vpu are present in LC3-positive compartments. We found that Vpu selectively interacts with the ATG8 ortholog LC3C through the Vpu L63VEM66 sequence...
November 22, 2016: Cell Reports
https://www.readbyqxmd.com/read/27879200/mechanism-of-cargo-directed-atg8-conjugation-during-selective-autophagy
#11
Dorotea Fracchiolla, Justyna Sawa-Makarska, Bettina Zens, Anita de Ruiter, Gabriele Zaffagnini, Andrea Brezovich, Julia Romanov, Kathrin Runggatscher, Claudine Kraft, Bojan Zagrovic, Sascha Martens
Selective autophagy is mediated by cargo receptors that link the cargo to the isolation membrane via interactions with Atg8 proteins. Atg8 proteins are localized to the membrane in an ubiquitin-like conjugation reaction, but how this conjugation is coupled to the presence of the cargo is unclear. Here we show that the S. cerevisiae Atg19, Atg34 and the human p62, Optineurin and NDP52 cargo receptors interact with the E3-like enzyme Atg12∼Atg5-Atg16, which stimulates Atg8 conjugation. The interaction of Atg19 with the Atg12∼Atg5-Atg16 complex is mediated by its Atg8-interacting motifs (AIMs)...
November 23, 2016: ELife
https://www.readbyqxmd.com/read/27878249/ets-1-a-potential-target-of-glycolysis-for-metabolic-therapy-by-regulating-glucose-metabolism-in-pancreatic-cancer
#12
Xiu Zhang, Dan Wu, Mohanad Aldarouish, Xiaodong Yin, Chunyan Li, Cailian Wang
Pancreatic cancer is one of the most lethal malignancies of all types of cancer due to lack of early symptoms and its resistance to conventional therapy. In our previous study, we have shown that v‑ets erythroblastosis virus E26 oncogene homolog‑1 (ETS‑1) promote cell migration and invasion in pancreatic cancer cells. However, the function of ETS‑1 in regulation of glycolysis and autophagy during progression of pancreatic cancer has not been defined yet. In this study, we sought to identify the potential role for silencing ETS‑1 in reducing the expression of glucose transporter‑1 (GLUT‑1) to disturb glycolysis through alteration of 'Warburg effect', by which could result in AMP‑activated protein kinase (AMPK) activation, autophagy induction and reduction of cell viability...
November 16, 2016: International Journal of Oncology
https://www.readbyqxmd.com/read/27875077/march5-rna-promotes-autophagy-migration-and-invasion-of-ovarian-cancer-cells
#13
Jianguo Hu, Ying Meng, Zhanqin Zhang, Qiuting Yan, Xingwei Jiang, Zilan Lv, Lina Hu
MARCH5 is a crucial regulator of mitochondrial fission. However, the expression and function of MARCH5 in ovarian cancer have not been determined. This study investigated the expression and function of MARCH5 in ovarian cancer with respect to its potential role in the tumorigenesis of the disease as well as its usefulness as an early diagnostic marker. We found that the expression of MARCH5 was substantially upregulated in ovarian cancer tissue in comparison with the normal control. Silencing MARCH5 in SKOV3 cells decreased TGFB1-induced cell macroautophagy/autophagy, migration, and invasion in vitro and in vivo, whereas the ectopic expression of MARCH5 in A2780 cells had the opposite effect...
November 22, 2016: Autophagy
https://www.readbyqxmd.com/read/27875067/transiently-expressed-atg16l1-inhibits-autophagosome-biogenesis-and-aberrantly-targets-rab11-positive-recycling-endosomes
#14
Jiehua Li, Zhixia Chen, Michael T Stang, Wentao Gao
The membrane source for autophagosome biogenesis is an unsolved mystery in the study of autophagy. ATG16L1 forms a complex with ATG12-ATG5 (the ATG16L1 complex). The ATG16L1 complex is recruited to autophagic membranes to convert MAP1LC3B-I to MAP1LC3B-II. The ATG16L1 complex dissociates from the phagophore before autophagosome membrane closure. Thus, ATG16L1 can be used as an early event marker for the study of autophagosome biogenesis. We found that among 3 proteins in the ATG16L1 complex, only ATG16L1 formed puncta-like structures when transiently overexpressed...
November 22, 2016: Autophagy
https://www.readbyqxmd.com/read/27874084/silymarin-attenuates-cigarette-smoke-extract-induced-inflammation-via-simultaneous-inhibition-of-autophagy-and-erk-p38-mapk-pathway-in-human-bronchial-epithelial-cells
#15
Diandian Li, Jun Hu, Tao Wang, Xue Zhang, Lian Liu, Hao Wang, Yanqiu Wu, Dan Xu, Fuqiang Wen
Cigarette smoke (CS) is a major risk of chronic obstructive pulmonary disease (COPD), contributing to airway inflammation. Our previous study revealed that silymarin had an anti-inflammatory effect in CS-exposed mice. In this study, we attempt to further elucidate the molecular mechanisms of silymarin in CS extract (CSE)-induced inflammation using human bronchial epithelial cells. Silymarin significantly suppressed autophagy activation and the activity of ERK/p38 mitogen-activated protein kinase (MAPK) pathway in Beas-2B cells...
November 22, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27867537/aquaporin-3-facilitates-chemoresistance-in-gastric-cancer-cells-to-cisplatin-via-autophagy
#16
Xuqiang Dong, Yao Wang, Yangchun Zhou, Jianfei Wen, Shoulin Wang, Lizong Shen
Cisplatin (cDDP) remains one of the first-line chemotherapeutic agents for gastric cancer (GC) treatment, and resistance to cDDP is the major limitation in its clinical application. Mechanisms of cDDP resistance have been shown to be varied and complicated. Aquaporin 3 (AQP3) has been demonstrated to be overexpressed in GC tissues and is thought to be involved in GC carcinogenesis and progression. However, the role of AQP3 in chemosensitivity of GC to cytotoxic agents remains unknown. In this study, we show that AQP3 overexpression induced resistance to cDDP in AGS cells (P<0...
2016: Cell Death Discovery
https://www.readbyqxmd.com/read/27863425/identification-of-an-hsp90-modulated-multi-step-process-for-erbb2-degradation-in-breast-cancer-cells
#17
Patrizio Castagnola, Grazia Bellese, Filippo Birocchi, Maria Cristina Gagliani, Carlo Tacchetti, Katia Cortese
The receptor tyrosine kinase ERBB2 interacts with HSP90 and is overexpressed in aggressive breast cancers. Therapeutic HSP90 inhibitors, i.e. Geldanamycin (GA), target ERBB2 to degradation. We have previously shown that HSP90 is responsible for the missorting of recycling ERBB2 to degradation compartments. In this study, we used biochemical, immunofluorescence and electron microscopy techniques to demonstrate that in SKBR3 human breast cancer cells, GA strongly induces polyubiquitination and internalization of the full-length p185-ERBB2, and promotes its cleavage, with the formation of a p116-ERBB2 form in EEA1-positive endosomes (EE)...
November 16, 2016: Oncotarget
https://www.readbyqxmd.com/read/27846905/rapamycin-regulates-autophagy-and-cell-adhesion-in-induced-pluripotent-stem-cells
#18
Areechun Sotthibundhu, Katya McDonagh, Alexander von Kriegsheim, Amaya Garcia-Munoz, Agnieszka Klawiter, Kerry Thompson, Kapil Dev Chauhan, Janusz Krawczyk, Veronica McInerney, Peter Dockery, Michael J Devine, Tilo Kunath, Frank Barry, Timothy O'Brien, Sanbing Shen
BACKGROUND: Cellular reprogramming is a stressful process, which requires cells to engulf somatic features and produce and maintain stemness machineries. Autophagy is a process to degrade unwanted proteins and is required for the derivation of induced pluripotent stem cells (iPSCs). However, the role of autophagy during iPSC maintenance remains undefined. METHODS: Human iPSCs were investigated by microscopy, immunofluorescence, and immunoblotting to detect autophagy machinery...
November 15, 2016: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/27846885/autophagy-is-associated-with-chemoresistance-in-neuroblastoma
#19
Assila Belounis, Carine Nyalendo, Roxane Le Gall, Tina V Imbriglio, Mohamed Mahma, Pierre Teira, Mona Beaunoyer, Sonia Cournoyer, Elie Haddad, Gilles Vassal, Hervé Sartelet
BACKGROUND: Neuroblastoma (NB) is a frequent pediatric tumor characterized by a poor prognosis where a majority of tumors progress despite intensive multimodality treatments. Autophagy, a self-degradative process in cells, could be induced by chemotherapy and be associated with chemoresistance. The aim of this study was to determine whether: 1) autophagy is present in NB, 2) chemotherapy modified its levels, and 3) its inhibition decreased chemoresistance. METHODS: Immunohistochemical stainings were performed on samples from 184 NB patients in order to verify the expression of LC3B, a specific marker for autophagy, and Beclin 1, a positive regulator of autophagy...
November 15, 2016: BMC Cancer
https://www.readbyqxmd.com/read/27845161/downregulation-of-autophagy-gene-expression-in-endometria-from-women-with-polycystic-ovary-syndrome
#20
Mirjana Sumarac-Dumanovic, Milica Apostolovic, Kristina Janjetovic, Danka Jeremic, Dusan Popadic, Aleksandar Ljubic, Jelena Micic, Jelena Dukanac-Stamenkovic, Aleksandra Tubic, Darko Stevanovic, Dragan Micic, Vladimir Trajkovic
Autophagy, a process of controlled cellular self-digestion, could be involved in cyclic remodeling of the human endometrium. We investigated endometrial mRNA expression of 23 autophagy-related (ATG) genes and transcription factors in healthy controls (n = 12) and anovulatory polycystic ovary syndrome (PCOS) patients (n = 24), as well as in their subgroup (n = 12) before and after metformin treatment. The mRNA levels of transcription factor forkhead box protein O1 (FOXO1) and several molecules involved in autophagosome formation (ATG13, RB1-inducible coiled-coil 1), autophagosome nucleation (ATG14, beclin 1, SH3-domain GRB2-like endophilin B1), autophagosome elongation (ATG3, ATG5, γ-aminobutyric acid receptor-associated protein - GABARAP), and delivery of ubiquitinated proteins to autophagosomes (sequestosome 1), were significantly reduced in anovulatory PCOS compared to healthy endometrium...
November 11, 2016: Molecular and Cellular Endocrinology
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