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https://www.readbyqxmd.com/read/29023824/cholangiocyte-autophagy-contributes-to-hepatic-cystogenesis-in-polycystic-liver-disease-and-represents-a-potential-therapeutic-target
#1
Anatoliy I Masyuk, Tatyana V Masyuk, Maria J Lorenzo Pisarello, Jingyi Francess Ding, Lorena Loarca, Bing Q Huang, Nicholas F LaRusso
Polycystic liver disease (PLD) is a group of genetic disorders with limited treatment and significant morbidity. Hepatic cysts arise from cholangiocytes exhibiting a hyperproliferative phenotype. Considering that hyperproliferation of many cell types is associated with alterations in autophagy, we hypothesized that autophagy is altered in PLD cholangiocytes, contributes to hepatic cystogenesis, and might represent a potential therapeutic target. We employed Functional Pathway Cluster Analysis (FPCA) and NextGen Sequencing (NGS), transmission electron microscopy, immunofluorescence confocal microscopy, and western blotting to assess autophagy in human and rodent PLD cholangiocytes...
October 10, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29022892/the-lncrna-hulc-functions-as-an-oncogene-by-targeting-atg7-and-itgb1-in-epithelial-ovarian-carcinoma
#2
Shuo Chen, Dan-Dan Wu, Xiu-Bo Sang, Li-Li Wang, Zhi-Hong Zong, Kai-Xuan Sun, Bo-Liang Liu, Yang Zhao
Highly upregulated in liver cancer (HULC) is a long noncoding RNA (lncRNA), which has recently been identified as a key regulator in the progression of hepatocellular carcinoma, gliomas and gastric cancer. However, its role in epithelial ovarian carcinoma (EOC) remains unknown. In this study, HULC expression was examined in EOC, borderline and benign ovarian tumors, and normal ovarian tissues by RT-PCR. Ovarian cancer cell phenotypes, as well as autophagy-associated proteins were examined after HULC overexpression or downregulation by plasmid or small interfering RNA (siRNA) transfection, respectively...
October 12, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28987884/co-delivery-of-autophagy-inhibitor-atg7-sirna-and-docetaxel-for-breast-cancer-treatment
#3
Chunai Gong, Chuling Hu, Fenfen Gu, Qingming Xia, Chong Yao, Lijuan Zhang, Lei Qiang, Shen Gao, Yuan Gao
The lysosomal degradation pathway of autophagy has a crucial role in protecting cancer cells from multiple endogenous and exogenous stresses, particularly during the pathogenesis of cancer. Accordingly, agents that inhibit autophagy may have broad therapeutic applications. We have developed a novel strategy based on co-delivery of an autophagy related 7 (ATG7) siRNA and docetaxel (DTX) in a crosslinked, reducible, peptide-based micellar system for breast cancer treatment. Our results show that DTX and siATG7 co-treatment exhibited 2...
October 5, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28985862/autophagy-negatively-regulates-pro-osteogenic-activity-in-human-aortic-valve-interstitial-cells
#4
Xin-Sheng Deng, Xianzhong Meng, Neil Venardos, Rui Song, Katsuhiro Yamanaka, David Fullerton, James Jaggers
BACKGROUND: Autophagy is a physiological process that plays an important role in maintaining cellular functions. When aortic valve interstitial cells (AVICs) are stimulated with inflammatory or mechanical stress, one response is elevated pro-osteogenic activity. We hypothesized that autophagy is important in the prevention or regulation of this pro-osteogenic activity in AVICs. MATERIALS AND METHODS: AVICs were isolated. Autophagy activity was examined and its role in AVIC's pro-osteogenic activity was determined using chemical inhibitors and genetic techniques...
October 2017: Journal of Surgical Research
https://www.readbyqxmd.com/read/28981380/astrocytes-promote-progression-of-breast-cancer-metastases-to-the-brain-via-a-kiss1-mediated-autophagy
#5
Natalya Kaverina, Anton V Borovjagin, Zaira Kadagidze, Anatoly Baryshnikov, Maria Baryshnikova, Dmitry Malin, Dhimankrishhna Ghosh, Nameeta Shah, Danny R Welch, Patrik Gabikian, Apollon Karseladze, Charles Cobbs, Ilya V Ulasov
Formation of metastases, also known as cancer dissemination, is an important stage of breast cancer (BrCa) development. KISS1 expression is associated with inhibition of metastases development. Recently we have demonstrated that BrCa metastases to the brain exhibit low levels of KISS1 expression at both mRNA and protein levels. By using multicolor immunofluorescence and coculture techniques here we show that normal adult astrocytes in the brain are capable of promoting metastatic transformation of circulating breast cancer cells localized to the brain through secretion of chemokine CXCL12...
October 5, 2017: Autophagy
https://www.readbyqxmd.com/read/28978809/dietary-potassium-regulates-vascular-calcification-and-arterial-stiffness
#6
Yong Sun, Chang Hyun Byon, Youfeng Yang, Wayne E Bradley, Louis J Dell'Italia, Paul W Sanders, Anupam Agarwal, Hui Wu, Yabing Chen
Vascular calcification is a risk factor that predicts adverse cardiovascular complications of several diseases including atherosclerosis. Reduced dietary potassium intake has been linked to cardiovascular diseases such as hypertension and incidental stroke, although the underlying molecular mechanisms remain largely unknown. Using the ApoE-deficient mouse model, we demonstrated for the first time to our knowledge that reduced dietary potassium (0.3%) promoted atherosclerotic vascular calcification and increased aortic stiffness, compared with normal (0...
October 5, 2017: JCI Insight
https://www.readbyqxmd.com/read/28978086/ampk-activation-dependent-autophagy-compromises-oleanolic-acid-induced-cytotoxicity-in-human-bladder-cancer-cells
#7
Yarong Song, Peng Zhang, Yadong Sun, Xuechao Li, Lifeng Chen, Yajun Xiao, Yifei Xing
Autophagy is an evolutionarily conserved catabolic process in eukaryotic cells, which allows cells to overcome a wide array of of stresses and has recently been shown to result in drug resistance. This study examined the effect of autophagy on oleanolic acid (OA)-induced cytotoxicity against bladder cancer cells. Our study demonstrated that OA inhibited cell viability, proliferation, and induced apoptosis in bladder cancer lines T24 and EJ. Furthermore, OA induced autophagy in both cell lines by activating AMP-activated protein kinase (AMPK), inhibiting mechanistic target of rapamycin (mTOR) and promoting unc-51 like autophagy activating kinase 1 (ULK1)...
September 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28974016/high-endogenous-accumulation-of-%C3%AF-3-polyunsaturated-fatty-acids-protect-against-ischemia-reperfusion-renal-injury-through-ampk-mediated-autophagy-in-fat-1-mice
#8
Do Hyeong Gwon, Tae Woong Hwang, Ju-Ye Ro, Yoon-Joong Kang, Jin Young Jeong, Do-Kyung Kim, Kyu Lim, Dong Woon Kim, Dae Eun Choi, Jwa-Jin Kim
Regulated autophagy is involved in the repair of renal ischemia-reperfusion injury (IRI). Fat-1 transgenic mice produce ω3-Polyunsaturated fatty acids (ω3-PUFAs) from ω6-Polyunsaturated fatty acids (ω6-PUFAs) without a dietary ω3-PUFAs supplement, leading to a high accumulation of omega-3 in various tissues. ω3-PUFAs show protective effects against various renal injuries and it has recently been reported that ω3-PUFAs regulate autophagy. We assessed whether ω3-PUFAs attenuated IR-induced acute kidney injury (AKI) and evaluated its associated mechanisms...
September 30, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28973896/mycobacterium-tuberculosis-is-protected-from-nadph-oxidase-and-lc3-associated-phagocytosis-by-the-lcp-protein-cpsa
#9
Stefan Köster, Sandeep Upadhyay, Pallavi Chandra, Kadamba Papavinasasundaram, Guozhe Yang, Amir Hassan, Steven J Grigsby, Ekansh Mittal, Heidi S Park, Victoria Jones, Fong-Fu Hsu, Mary Jackson, Christopher M Sassetti, Jennifer A Philips
Mycobacterium tuberculosis' success as a pathogen comes from its ability to evade degradation by macrophages. Normally macrophages clear microorganisms that activate pathogen-recognition receptors (PRRs) through a lysosomal-trafficking pathway called "LC3-associated phagocytosis" (LAP). Although Mtuberculosis activates numerous PRRs, for reasons that are poorly understood LAP does not substantially contribute to Mtuberculosis control. LAP depends upon reactive oxygen species (ROS) generated by NADPH oxidase, but Mtuberculosis fails to generate a robust oxidative response...
September 27, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28963374/protective-effect-of-autophagy-on-endoplasmic-reticulum-stress-induced-apoptosis-of-alveolar-epithelial-cells-in-rat-models-of-copd
#10
Yao Tang, Qi-Hang Cai, Yong-Jian Wang, Shao-Hua Fan, Zi-Feng Zhang, Meng-Qi Xiao, Jin-Yu Zhu, Dong-Mei Wu, Jun Lu, Yuan-Lin Zheng
During this study, we explored the protective effects of autophagy on endoplasmic reticulum stress (ERS)-induced apoptosis belonging to alveolar epithelial cells (AECs) in rat models with chronic obstructive pulmonary disease (COPD). Fifty-six 12-week-old male Sprague-Dawley (SD) rats were randomly assigned into the COPD group (rats exposed to cigarette smoke), the 3-methyladenine (3-MA) intervention group (COPD rats were administrated with 10 mg/kg autophagy inhibitors), the chloroquine (CQ)-intervention group (COPD rats were administrated with 40 mg/kg CQ) and the control group (rats breathed in normal saline)...
September 29, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/28955784/cyclic-mechanical-stretch-contributes-to-network-development-of-osteocyte-like-cells-with-morphological-change-and-autophagy-promotion-but-without-preferential-cell-alignment-in-rat
#11
Nao Inaba, Shinichiro Kuroshima, Yusuke Uto, Muneteru Sasaki, Takashi Sawase
Osteocytes play important roles in controlling bone quality as well as preferential alignment of biological apatite c-axis/collagen fibers. However, the relationship between osteocytes and mechanical stress remains unclear due to the difficulty of three-dimensional (3D) culture of osteocytes in vitro. The aim of this study was to investigate the effect of cyclic mechanical stretch on 3D-cultured osteocyte-like cells. Osteocyte-like cells were established using rat calvarial osteoblasts cultured in a 3D culture system...
September 2017: Biochemistry and Biophysics Reports
https://www.readbyqxmd.com/read/28954454/autophagy-inhibition-increased-the-anti-tumor-effect-of-cisplatin-on-drug-resistant-esophageal-cancer-cells
#12
C Y Cheng, J C Liu, J J Wang, Y H Li, J Pan, Y R Zhang
The sensitivity of tumor cells to treatment can be affected by autophagy. The drug resistance of esophageal cancer cells against cisplatin occurs during the long period of chemotherapy drug treatment. This study was designed to observe the effect autophagy has on the occurrence of esophageal cancer cell drug resistance against cisplatin and investigate its molecular mechanism in order to provide new details and strategies for the clinical treatment of esophageal cancer, especially cisplatin treatment. The detection methods used in this study were 3-(4,5-dimethylthiazd-2-yl)-2,5-dipheny-ltetrazolium bromide (MTT) colorimetric assay, clone survival technique, small interfering RNA (siRNA) transfection, and Western blot...
July 2017: Journal of Biological Regulators and Homeostatic Agents
https://www.readbyqxmd.com/read/28949785/avian-metapneumovirus-subgroup-c-induces-autophagy-through-the-atf6-upr-pathway
#13
Lei Hou, Li Wei, Shanshan Zhu, Jing Wang, Rong Quan, Zixuan Li, Jue Liu
An increasing number of studies have demonstrated that macroautophagy/autophagy plays an important role in the infectious processes of diverse pathogens. However, it remains unknown whether autophagy is induced in avian metapneumovirus (aMPV)-infected host cells, and, if so, how this occurs. Here, we report that aMPV subgroup C (aMPV/C) induces autophagy in cultured cells. We demonstrated this relationship by detecting classical autophagic features, including the formation of autophagsomes, the presence of GFP-LC3 puncta and the conversation of LC3-I into LC3-II...
October 3, 2017: Autophagy
https://www.readbyqxmd.com/read/28944928/hydrogen-inhibits-isoproterenol%C3%A2-induced-autophagy-in-cardiomyocytes-in%C3%A2-vitro-and-in%C3%A2-vivo
#14
Yaxing Zhang, Zhiyuan Long, Jingting Xu, Sihua Tan, Nan Zhang, Anfei Li, Ling Wang, Tinghuai Wang
A previous study from our group has demonstrated that hydrogen administration can attenuate cardiovascular hypertrophy in vivo by targeting reactive oxygen species‑dependent mitogen‑activated protein kinase signaling. The aim of the present study is to determine the effect of hydrogen on cardiomyocyte autophagy during β‑adrenoceptor activation in vivo and in vitro. We prepared hydrogen‑rich medium, and the concentration of hydrogen was measured by using the MB‑Pt reagent method. For the in vitro study, H9c2 cardiomyocytes were stimulated with isoproterenol (ISO; 10 µM) for 5, 15 and 30 min, and then the protein expression levels of the autophagy marker microtubule‑associated protein 1 light chain 3β II (LC3B II) were examined by western blotting...
September 25, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28944925/autophagy-is-activated-to-protect-renal-tubular-epithelial-cells-against-iodinated-contrast-media%C3%A2-induced-cytotoxicity
#15
Na Liu, Rong Lei, Mi-Mi Tang, Wei Cheng, Min Luo, Qian Xu, Shao-Bin Duan
With the steady increase in the use of various contrast‑related technologies in recent years, contrast‑induced nephropathy has received significant attention from clinicians and researchers. The present study aimed to determine the potential role of autophagy in iodinated contrast media (CM)‑induced cell injury and apoptosis in human proximal renal tubular epithelial HK‑2 cells. The present study used the iodinated CM iohexol (200 mg iodine/ml) to treat HK‑2 cells for 6 h, in order to establish a damaged cell model...
September 25, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28935975/tumor-necrosis-factor-inducible-gene-6-protein-ameliorates-chronic-liver-damage-by-promoting-autophagy-formation-in-mice
#16
Sihyung Wang, Chanbin Lee, Jieun Kim, Jeongeun Hyun, Minso Lim, Hyuk-Jin Cha, Seh-Hoon Oh, Yung Hyun Choi, Youngmi Jung
Tumor necrosis factor-inducible gene 6 protein (TSG-6) has recently been shown to protect the liver from acute damage. However, the mechanism underlying the effect of TSG-6 on the liver remains unclear. Autophagy is a catabolic process that targets cell components to lysosomes for degradation, and its functions are reported to be dysregulated in liver diseases. Here we investigate whether TSG-6 promotes liver regeneration by inducing autophagic clearance in damaged livers. Mice fed a methionine choline-deficient diet supplemented with 0...
September 22, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28933629/ezetimibe-ameliorates-steatohepatitis-via-amp-activated-protein-kinase-tfeb-mediated-activation-of-autophagy-and-nlrp3-inflammasome-inhibition
#17
Soo Hyun Kim, Gyuri Kim, Dai Hoon Han, Milim Lee, Irene Kim, Bohkyung Kim, Kook Hwan Kim, Young-Mi Song, Jeong Eun Yoo, Hye Jin Wang, Soo Han Bae, Yong-Ho Lee, Byung-Wan Lee, Eun Seok Kang, Bong-Soo Cha, Myung-Shik Lee
Impairment in macroautophagy/autophagy flux and inflammasome activation are common characteristics of nonalcoholic steatohepatitis (NASH). Considering the lack of approved agents for treating NASH, drugs that can enhance autophagy and modulate inflammasome pathways may be beneficial. Here, we investigated the novel mechanism of ezetimibe, a widely prescribed drug for hypercholesterolemia, as a therapeutic option for ameliorating NASH. Human liver samples with steatosis and NASH were analyzed. For in vitro studies of autophagy and inflammasomes, primary mouse hepatocytes, human hepatoma cells, mouse embryonic fibroblasts with Ampk or Tsc2 knockout, and human or primary mouse macrophages were treated with ezetimibe and palmitate...
October 3, 2017: Autophagy
https://www.readbyqxmd.com/read/28933598/autophagy-gene-atg7-regulates-ultraviolet-radiation-induced-inflammation-and-skin-tumorigenesis
#18
Lei Qiang, Ashley Sample, Christopher R Shea, Keyoumars Soltani, Kay F Macleod, Yu-Ying He
Macroautophagy (hereafter autophagy) is a cellular "self-eating" process that is implicated in many human cancers, where it can act to either promote or suppress tumorigenesis. However, the role of autophagy in regulation of inflammation during tumorigenesis remains unclear. Here we show that autophagy is induced in the epidermis by ultraviolet (UV) irradiation and autophagy gene Atg7 promoted UV-induced inflammation and skin tumorigenesis. Atg7 regulated UV-induced cytokine expression and secretion, and promoted Ptgs2/Cox-2 expression through both a CREB1/CREB-dependent cell autonomous mechanism and an IL1B/IL1β-dependent non-cell autonomous mechanism...
September 21, 2017: Autophagy
https://www.readbyqxmd.com/read/28927939/autophagy-inhibition-enhances-antiproliferative-effect-of-salinomycin-in-pancreatic-cancer-cells
#19
Sho Endo, Kohei Nakata, Akiko Sagara, Kazuhiro Koikawa, Yohei Ando, Shin Kibe, Shin Takesue, Hiromichi Nakayama, Toshiya Abe, Takashi Okumura, Taiki Moriyama, Yoshihiro Miyasaka, Kenoki Ohuchida, Takao Ohtsuka, Kazuhiro Mizumoto, Masafumi Nakamura
BACKGROUND: Salinomycin has cytotoxic effects on various types of malignancy and induces autophagy. However, it has not been clarified whether autophagy induced by salinomycin treatment has a protective or cytotoxic role. We investigated whether salinomycin affects autophagy in pancreatic cancer cells and whether autophagy induced by salinomycin treatment has a protective or cytotoxic role in these cells. METHODS: We investigated the effect of salinomycin using three pancreatic cancer cell lines...
August 25, 2017: Pancreatology: Official Journal of the International Association of Pancreatology (IAP) ... [et Al.]
https://www.readbyqxmd.com/read/28924380/intracellular-insulin-and-impaired-autophagy-in-a-zebrafish-model-and-a-cell-model-of-type-2-diabetes
#20
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
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