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https://www.readbyqxmd.com/read/29453806/cq-sensitizes-human-pancreatic-cancer-cells-to-gemcitabine-through-the-lysosomal-apoptotic-pathway-via-reactive-oxygen-species
#1
Zhiping Fu, Cheng Xi, Jie Kuang, Haoran Feng, Lingxie Chen, Juyong Liang, Xiaonan Shen, Stanley Yuen, Peng Chenghong, Shen Baiyong, Jin Zhijian, Weihua Qiu
As an established anti-cancer drug, gemcitabine (GEM) is an effective systemic treatment for advanced pancreatic cancer (PC). However, little is known about the potential effectors that may modify tumour cell sensitivity towards GEM. Autophagy, as a physiological cellular mechanism, is involved in both cell survival and cell death. In this study, we found that exposure to GEM induced a significant increase in autophagy in a dose-dependent manner in PANC-1 and BxPC-3 cells. Inhibition of autophagy by chloroquine (CQ) and ATG7 siRNA increased GEM-induced cytotoxicity, and CQ was more effective than ATG7 siRNA...
February 17, 2018: Molecular Oncology
https://www.readbyqxmd.com/read/29452162/pseudorabies-virus-induces-autophagy-to-enhance-viral-replication-in-mouse-neuro-2a-cells-in-vitro
#2
Changmeng Xu, Mi Wang, Zhongbao Song, Zhijian Wang, Qianyu Liu, Ping Jiang, Juan Bai, Yufeng Li, Xianwei Wang
Autophagy of cytoplasmic components plays an essential role in the pathogenic infection process. Furthermore, research suggests that autophagy is an extremely important component of the innate immune response. Our study aimed to reveal the effect of virus-induced autophagy on pseudorabies virus (PRV) replication. Our results confirmed that light chain 3 (LC3)-I was converted into LC3-II after PRV infection; this transition is considered an important indicator of autophagy. Transmission electron microscopy (TEM) revealed that PRV infection could notably increase the number of autophagosomes in mouse neuro-2a (N2a) cells...
February 13, 2018: Virus Research
https://www.readbyqxmd.com/read/29435112/lncrna-malat1-regulates-smooth-muscle-cell-phenotype-switch-via-activation-of-autophagy
#3
Tie-Feng Song, Li-Wen Huang, Ying Yuan, Hui-Qin Wang, Hong-Peng He, Wen-Jian Ma, Li-Hong Huo, Hao Zhou, Nan Wang, Tong-Cun Zhang
Vascular smooth muscle cells (VSMCs), switching from a differentiated to a proliferative phenotype, contribute to various vascular diseases. However, the role of long noncoding RNA metastasis-associated lung adenocarcinoma transcript 1 MALAT1 in the phenotype switching of VSMCs remains unclear. Here, we report that the knockdown of MALAT1 promotes the transformation of smooth muscle cells from a proliferative phenotype to a differentiated phenotype. MALAT1 knockdown inhibited cellular proliferation and migration, leading to significant cell cycle arrest in the G2 phase...
January 12, 2018: Oncotarget
https://www.readbyqxmd.com/read/29424891/autophagy-suppresses-the-proliferation-of-renal-carcinoma-cell
#4
Z-L Wang, Q Deng, T Chong, Z-M Wang
OBJECTIVE: To investigate the effetcs of autophagy on the proliferation of renal carcinoma (RCCs). MATERIALS AND METHODS: Authophagy related protein 7 (Atg7)-overexpressing and knockdown RCC cell lines were established using lentiviral transfection and shRNA interference, respectively. (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) (MTT) was used to determine the Cell growth rate, and western blot was used to determine the expression of protein...
January 2018: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/29414645/activation-of-autophagy-is-required-for-oroxylin-a-to-alleviate-carbon-tetrachloride-induced-liver-fibrosis-and-hepatic-stellate-cell-activation
#5
Weiwei Chen, Zili Zhang, Zhen Yao, Ling Wang, Feng Zhang, Jiangjuan Shao, Anping Chen, Shizhong Zheng
Liver fibrosis is a reversible pathophysiological process correlated with intense repair and cicatrization mechanisms, and its end-stage cirrhosis is responsible for high morbidity and mortality worldwide. Interestingly, the use of natural products as a realistic option for the treatment of liver fibrosis has broadly been accepted. Oroxylin A, a safe and natural product, shows a wide range of pharmacological activities such as anti-inflammatory, anti-oxidant, and anti-tumor properties. However, the effects of Oroxylin A on liver fibrosis remain poorly understood...
January 24, 2018: International Immunopharmacology
https://www.readbyqxmd.com/read/29414598/combination-of-hindlimb-suspension-and-immobilization-by-casting-exaggerates-sarcopenia-by-stimulating-autophagy-but-does-not-worsen-osteopenia
#6
Toni L Speacht, Andrew R Krause, Jennifer L Steiner, Charles H Lang, Henry J Donahue
Astronauts in space experience a unique environment that causes the concomitant loss of bone and muscle. However, the interaction between these tissues and how osteopenia and sarcopenia affect each other is unclear. We explored this relationship by exaggerating unloading-induced muscle loss using a unilateral casting model in conjunction with hindlimb suspension (HLS). Five-month-old, male C57Bl/6J mice subjected to HLS for 2 weeks displayed a significant decrease in gastrocnemius and quadriceps weight (-9-10%), with a two-fold greater decrease in muscle mass observed in the HLS + casted limb...
February 2, 2018: Bone
https://www.readbyqxmd.com/read/29405784/carvacrol-nanoemulsion-evokes-cell-cycle-arrest-apoptosis-induction-and-autophagy-inhibition-in-doxorubicin-resistant-a549-cell-line
#7
Imran Khan, Ashutosh Bahuguna, Monika Bhardwaj, Tejinder Pal Khaket, Sun Chul Kang
Carvacrol is a monoterpenoid flavonoid found abundantly in thyme plants. Its physiochemical instability and partial solubility in water is the principal limitation for its industrial use. Hence, we made a carvacrol nanoemulsion (CANE) using ultrasonication method and characterized it by dynamic light scattering (DLS) technique which revealed a negative surface charge (-29.89 mV) with 99.1 nm average droplet size. CANE effectively induced apoptosis in doxorubicin-resistant A549 lung carcinoma cells (A549 DR ) evident by the elevated expression of apoptotic proteins such as Bax, Cytochrome C, and Cleaved caspase 3 and 9...
February 6, 2018: Artificial Cells, Nanomedicine, and Biotechnology
https://www.readbyqxmd.com/read/29400609/adipose-tissue-autophagy-related-gene-expression-is-associated-with-glucometabolic-status-in-human-obesity
#8
Qing Xu, Edwin C M Mariman, Nadia J T Roumans, Roel G Vink, Gijs H Goossens, Ellen E Blaak, Johan W E Jocken
Adipose tissue autophagy (AT) is associated with human obesity and increased metabolic risk. Recent findings establish a role for autophagy in lipid metabolism. Here, we compared the expression of autophagy-related and lipolysis genes in human abdominal subcutaneous AT (SCAT) in overweight/obese subjects (n = 17) with or without impaired glucose tolerance in comparison with lean normal glucose tolerant individuals (n = 9), and investigated the association between AT autophagy and lipolysis. Human multipotent adipose-derived stem cells (hMADS) were used to investigate the effect of pharmacological HSL inhibition on changes in the autophagic flux...
February 5, 2018: Adipocyte
https://www.readbyqxmd.com/read/29392448/effect-of-zinc-intake-on-hepatic-autophagy-during-acute-alcohol-intoxication
#9
Juan P Liuzzi, Vijaya Narayanan, Huong Doan, Changwon Yoo
Autophagy is a conserved mechanism that plays a housekeeping role by eliminating protein aggregates and damaged organelles. Recent studies have demonstrated that acute ethanol intoxication induces hepatic autophagy in mice. The effect of dietary zinc intake on hepatic autophagic flux during ethanol intoxication has not been evaluated using animal models. Herein, we investigated whether zinc deficiency and excess can affect autophagic flux in the liver in mice and in human hepatoma cells acutely exposed to ethanol...
February 1, 2018: Biometals: An International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine
https://www.readbyqxmd.com/read/29386287/rsv-replication-is-promoted-by-autophagy-mediated-inhibition-of-apoptosis
#10
Miao Li, Jian Li, Jianling Yang, Jianguo Liu, Zhengzheng Zhang, Xiaotian Song, Zhiyan Yao, Cuiqing Ma, Wenjian Li, Ruihong Zeng, Kai Wang, Lin Wei
Respiratory syncytial virus (RSV) is the main cause of acute lower respiratory tract infection (ALRI) in children worldwide. Virus-host interaction affects progression and prognosis of the infection. Autophagy plays important roles in virus-host interaction. Respiratory epithelial cells serve as the front line of host defense during RSV infection, However, it is still unclear how they interact with RSV. In this study, We found that RSV induced autophagy which favored RSV replication and exacerbated lung pathology in vivo Mechanistically, RSV induced complete autophagy flux through Reactive oxygen species (ROS) generation and activation of AMPK-MTOR (AMP-activated protein kinase/mammalian target of rapamycin) signaling pathway in Hep2 cells...
January 31, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29383879/clostridium-difficile-toxin-b-induces-autophagic-cell-death-in-colonocytes
#11
Hung Chan, Shan Zhao, Lin Zhang, Jeffery Ho, Czarina C H Leung, Wai T Wong, Yuanyuan Tian, Xiaodong Liu, Thomas N Y Kwong, Raphael C Y Chan, Sidney S B Yu, Maggie H T Wang, Gary Tse, Sunny H Wong, Matthew T V Chan, William K K Wu
Toxin B (TcdB) is a major pathogenic factor of Clostridum difficile. However, the mechanism by which TcdB exerts its cytotoxic action in host cells is still not completely known. Herein, we report for the first time that TcdB induced autophagic cell death in cultured human colonocytes. The induction of autophagy was demonstrated by the increased levels of LC3-II, formation of LC3+ autophagosomes, accumulation of acidic vesicular organelles and reduced levels of the autophagic substrate p62/SQSTM1. TcdB-induced autophagy was also accompanied by the repression of phosphoinositide 3-kinase (PI3K)/Akt/mechanistic target of rapamycin (mTOR) complex 1 activity...
January 31, 2018: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29377765/autophagy-contributes-to-sulfonylurea-herbicide-tolerance-via-gcn2-independent-regulation-of-amino-acid-homeostasis
#12
Lun Zhao, Li Deng, Qing Zhang, Xue Jing, Meng Ma, Bin Yi, Jing Wen, Chaozhi Ma, Jinxing Tu, Tingdong Fu, Jinxiong Shen
Sulfonylurea (SU) herbicides inhibit branched-chain amino acid (BCAA) biosynthesis by targeting acetolactate synthase. Plants have evolved target-site resistance and metabolic tolerance to SU herbicides; the GCN2 (general control non-repressible 2) pathway is also involved in SU tolerance. Here, we report a novel SU tolerance mechanism, autophagy, which we call 'homeostatic tolerance,' is involved in amino acid signaling in Arabidopsis. The activation and reversion of autophagy and GCN2 by the SU herbicide tribenuron-methyl (TM) and exogenous BCAA, respectively, confirmed that TM-induced BCAA starvation is responsible for the activation of autophagy and GCN2...
January 29, 2018: Autophagy
https://www.readbyqxmd.com/read/29370693/biological-roles-of-alternative-autophagy
#13
REVIEW
Shigeomi Shimizu
Atg5 and Atg7 have long been considered as essential molecules for autophagy. However, we found that cells lacking these molecules still form autophagic vacuoles and perform autophagic protein degradation when subjected to certain stressors. During this unconventional autophagy pathway, autophagosomes appeared to be generated in a Rab9-dependent manner by the fusion of vesicles derived from the trans-Golgi and late endosomes. Therefore, mammalian autophagy can occur via at least two different pathways; the Atg5/Atg7-dependent conventional pathway and an Atg5/Atg7-independent alternative pathway...
January 31, 2018: Molecules and Cells
https://www.readbyqxmd.com/read/29368299/autophagic-flux-is-essential-for-the-downregulation-of-d-dopachrome-tautomerase-by-atractylenolide-i-to-ameliorate-intestinal-adenoma-formation
#14
Lu Li, Linlin Jing, Junjiang Wang, Wenjuan Xu, Xianling Gong, Yiye Zhao, Ye Ma, Xueqing Yao, Xuegang Sun
Colorectal cancer is generally believed to progress through an adenoma - carcinoma sequence. Adenomatous polyposis coli (APC) mutations serve as the initiating event in adenoma formation. The Apc Min/+ mouse harbors a mutation in the APC gene, which is similar or identical to the mutation found in individuals with familial adenomatous polyposis and 70% of all sporadic CRC cases. Autophagy is a constitutive process required for proper cellular homeostasis. However, its role in intestinal adenoma formation is still controversial...
January 24, 2018: Journal of Cell Communication and Signaling
https://www.readbyqxmd.com/read/29365132/transcriptional-stimulation-of-rate-limiting-components-of-the-autophagic-pathway-improves-plant-fitness
#15
Elena A Minina, Panagiotis N Moschou, Ramesh R Vetukuri, Victoria Sanchez-Vera, Catarina Cardoso, Qinsong Liu, Pernilla H Elander, Kerstin Dalman, Mirela Beganovic, Jenny Lindberg Yilmaz, Sofia Marmon, Lana Shabala, Maria F Suarez, Karin Ljung, Ondrej Novák, Sergey Shabala, Sten Stymne, Daniel Hofius, Peter V Bozhkov
Autophagy is a major catabolic process whereby autophagosomes deliver cytoplasmic content to the lytic compartment for recycling. Autophagosome formation requires two ubiquitin-like systems conjugating Atg12 with Atg5 and Atg8 with lipid phosphatidylethanolamine (PE), respectively. Genetic suppression of these systems causes autophagy-deficient phenotypes with reduced fitness and longevity. We show that Atg5 and E1-like enzyme, Atg7, are rate-limiting components of the Atg8-PE conjugation in Arabidopsis. Overexpression of ATG5 or ATG7 stimulates Atg8 lipidation, autophagosome formation and autophagic flux...
January 20, 2018: Journal of Experimental Botany
https://www.readbyqxmd.com/read/29364854/cytoprotective-mechanisms-in-fatty-liver-preservation-against-cold-ischemia-injury-a-comparison-between-igl-1-and-htk
#16
Arnau Panisello-Roselló, Eva Verde, Alexandre Lopez, Marta Flores, Emma Folch-Puy, Anabela Rolo, Carlos Palmeira, Georgina Hotter, Teresa Carbonell, René Adam, Joan Roselló-Catafau
Institute Goeorges Lopez 1 (IGL-1) and Histidine-Tryptophan-Ketoglutarate (HTK) preservation solutions are regularly used in clinical for liver transplantation besides University of Wisconsin (UW) solution and Celsior. Several clinical trials and experimental works have been carried out comparing all the solutions, however the comparative IGL-1 and HTK appraisals are poor; especially when they deal with the underlying protection mechanisms of the fatty liver graft during cold storage. Fatty livers from male obese Zücker rats were conserved for 24 h at 4 °C in IGL-1 or HTK preservation solutions...
January 24, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29362360/sensitisation-to-mitoxantrone-induced-apoptosis-by-the-oncolytic-adenovirus-ad%C3%A2-%C3%A2-through-bcl-2-dependent-attenuation-of-autophagy
#17
Carmen Aguirre-Hernández, Héctor Maya-Pineda, Julia San Millán, Y K Stella Man, Yong-Jie Lu, Gunnel Halldén
Anti-apoptotic Bcl-2 is frequently activated in human malignant cells to promote cell survival and inhibit cell death. Replication-selective oncolytic adenoviruses deleted in the functional Bcl-2 homologue E1B19K potently synergise with apoptosis-inducing chemotherapeutic drugs, including mitoxantrone for prostate cancer. Here, we demonstrate that our previously generated oncolytic mutant Ad∆∆ (E1B19K- and E1ACR2-deleted) caused potent synergistic apoptotic cell death in both drug-sensitive 22Rv1, and drug-insensitive PC3 and PC3M prostate cancer cells...
January 24, 2018: Oncogenesis
https://www.readbyqxmd.com/read/29361668/cutaneous-exposure-to-lewisite-causes-acute-kidney-injury-by-invoking-dna-damage-and-autophagic-response
#18
Ritesh Srivastava, Amie M Traylor, Changzhao Li, Wenguang Feng, Lingling Guo, Veena B Antony, Trenton R Schoeb, Anupam Agarwal, Mohammad Athar
Lewisite (2-chlorovinyldichloroarsine) is an organic and arsenical chemical warfare agent which was developed and weaponized during World Wars I/II. Stockpiles of lewisite still exist in many parts of the world and pose potential environmental and human health threat. Exposure to lewisite and similar chemicals causes intense cutaneous inflammatory response. However, morbidity and mortality in the exposed population is not only due to cutaneous damage but is also a result of systemic injury. Here, we provide data delineating the pathogenesis of acute kidney injury (AKI) following cutaneous exposure to lewisite and its analogue phenylarsine oxide (PAO) in a murine model...
January 17, 2018: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29358506/blockade-of-histone-deacetylase-6-protects-against-cisplatin-induced-acute-kidney-injury
#19
Jinhua Tang, Yingfeng Shi, Na Liu, Liuqing Xu, Xiujuan Zang, Peibin Li, Juanlian Zhang, Xiaoqing Zheng, Andong Qiu, Shougang Zhuang
Histone deacetylase 6 (HDAC6) has been shown to be involved in various pathological conditions, including cancer, neurodegenerative disorders and inflammatory diseases. Nonetheless, its specific role in drug-induced nephrotoxicity is poorly understood. Cisplatin (dichlorodiamino platinum) belongs to an inorganic platinum-fundamental chemotherapeutic drug utilized in the therapy of various solid malignant tumors. However, the use of cisplatin is limited by obvious side effects. In this study, we utilized a murine model of cisplatin-induced acute kidney injury (AKI) and a highly selective inhibitor of HDAC6, tubastatin A (TA), to assess the role of HDAC6 in nephrotoxicity and its associated mechanisms...
January 22, 2018: Clinical Science (1979-)
https://www.readbyqxmd.com/read/29355734/inhibition-of-autophagy-potentiates-the-apoptosis-inducing-effects-of-photodynamic-therapy-on-human-colon-cancer-cells
#20
Guoqing Ouyang, Li Xiong, Zhipeng Liu, Brandon Lam, Brian Bui, Lun Ma, Xiang Chen, Pan Zhou, Kunpeng Wang, Zijian Zhang, He Huang, Xiongying Miao, Wei Chen, Yu Wen
BACKGROUND: Photodynamic therapy (PDT) has been reported to be a promising therapy for colon cancer because of its substantial safety features and its ability to induce a systematic reaction rather than local effects on the focal lesion in the intestine. Autophagy and apoptosis play important roles in the response to PDT. However, the role of autophagy after PDT treatment has not yet been clarified. METHODS: In this study, we investigated the relationship between apoptosis and autophagy in porphyrin IX (PpIX)-mediated PDT (PpIX-PDT) in HCT116 colon cancer cells...
January 17, 2018: Photodiagnosis and Photodynamic Therapy
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