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https://www.readbyqxmd.com/read/29352609/induction-of-mitophagy-in-the-hei-oc1-auditory-cell-line-and-activation-of-the-atg12-lc3-pathway-in-the-organ-of-corti
#1
Cristian Setz, Anne-Sophie Benischke, Anna Catharina Pinho Ferreira Bento, Yves Brand, Soledad Levano, Franziska Paech, Katharina Leitmeyer, Daniel Bodmer
Autophagy is a highly evolutionary conserved quality control defense mechanism within cells, which has also been implicated in cell death processes. In the mammalian inner ear, autophagy has been shown to play a role during early morphogenesis as well as in adult cochlear hair cells exposed to ototoxic insults. Mitophagy, a selective autophagic cell process targeting mitochondria, hasn't been studied in the inner ear so far. On this work, we searched for molecular indicators of mitophagy within House Ear Institute-Organ of Corti-1 (HEI-OC1) cells as well as in the organ of Corti (OC)...
January 11, 2018: Hearing Research
https://www.readbyqxmd.com/read/29352110/melatonin-inhibits-apoptotic-cell-death-induced-by-vibrio-vulnificus-vvha-via-melatonin-receptor-2-coupling-with-ncf-1
#2
Sei-Jung Lee, Hyun Jik Lee, Young Hyun Jung, Jun Sung Kim, Sang Ho Choi, Ho Jae Han
Melatonin, an endogenous hormone molecule, has a variety of biological functions, but a functional role of melatonin in the infection of Gram-negative bacterium Vibrio vulnificus has yet to be described. In this study, we investigated the molecular mechanism of melatonin in the apoptosis of human intestinal epithelial (HCT116) cells induced by the hemolysin (VvhA) produced by V. vulnificus. Melatonin (1 μM) significantly inhibited apoptosis induced by the recombinant protein (r) VvhA, which had been inhibited by the knockdown of MT2...
January 19, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29346066/expression-of-autophagy-related-genes-in-chronic-lymphocytic-leukemia-is-associated-with-disease-course
#3
Yi-Lin Kong, Ying Huang, Jia-Zhu Wu, Xin Cao, Jin-Hua Liang, Yi Xia, Wei Wu, Lei Cao, Hua-Yuan Zhu, Li Wang, Lei Fan, Jian-Yong Li, Wei Xu
Autophagy leads cells to different fates in various cell types and under diverse contexts. Chronic lymphocytic leukemia (CLL), an incurable hematologic neoplasm, has highly variable course and its heterogeneity prompts interest in exploring autophagic trajectories in CLL. We detected the mRNA levels of two autophagy-related genes, BECN1 and ATG5, assessed the association between expression levels and clinical characteristics, and did survival analysis. One hundred and six patients with CLL and fifty healthy controls were enrolled in the present study...
January 3, 2018: Leukemia Research
https://www.readbyqxmd.com/read/29333953/the-irreversible-erbb1-2-4-inhibitor-neratinib-interacts-with-the-bcl-2-inhibitor-venetoclax-to-kill-mammary-cancer-cells
#4
Laurence Booth, Jane L Roberts, Francesca Avogadri-Connors, Richard E CutlerJr, Alshad S Lalani, Andrew Poklepovic, Paul Dent
The irreversible ERBB1/2/4 inhibitor, neratinib, down-regulates the expression of ERBB1/2/4 as well as the levels of MCL-1 and BCL-XL. Venetoclax (ABT199) is a BCL-2 inhibitor. At physiologic concentrations neratinib interacted in a synergistic fashion with venetoclax to kill HER2+ and TNBC mammary carcinoma cells. This was associated with the drug-combination: reducing the expression and phosphorylation of ERBB1/2/3; in an eIF2α-dependent fashion reducing the expression of MCL-1 and BCL-XL and increasing the expression of Beclin1 and ATG5; and increasing the activity of the ATM-AMPKα-ULK1 S317 pathway which was causal in the formation of toxic autophagosomes...
January 15, 2018: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/29328502/hepatocellular-carcinoma-related-cyclin-d1-is-selectively-regulated-by-autophagy-degradation-system
#5
Shan-Ying Wu, Sheng-Hui Lan, Shang-Rung Wu, Yen-Chi Chiu, Xi-Zhang Lin, Ih-Jen Su, Ting-Fen Tsai, Chia-Jui Yen, Tsung-Hsueh Lu, Fu-Wen Liang, Chung-Yi Li, Huey-Jen Su, Chun-Li Su, Hsiao-Sheng Liu
Dysfunction of degradation machineries causes cancers, including hepatocellular carcinoma (HCC). Overexpression of cyclin D1 in HCC has been reported. We previously reported that autophagy preferentially recruits and degrades the oncogenic miR-224 to prevent HCC. Therefore, in the present study we attempted to clarify whether cyclin D1 is another oncogenic factor selectively regulated by autophagy in HCC tumorigenesis. Initially, we found an inverse correlation between low autophagic activity and high cyclin D1 expression in the tumors of 147 HCC patients and three murine models, and these results taken together revealed a correlation with poor overall survival of HCC patients, indicating the importance of these two events in HCC development...
January 12, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29328494/pterostilbene-inhibits-reactive-oxygen-species-production-and-apoptosis-in-primary-spinal-cord-neurons-by-activating-autophagy-via-the-mechanistic-target-of-rapamycin-signaling-pathway
#6
Jing-Lan He, Xiao-Hui Dong, Zong-Hu Li, Xiao-Ying Wang, Zhi-An Fu, Na Shen
Autophagy is an important self-adaptive mechanism that is involved in inhibiting reactive oxygen species (ROS) in spinal cord neurons. Pterostilbene, a natural plant extract, has been demonstrated to possess antioxidant effects; however, it has not yet been investigated whether pterostilbene could activate autophagy and protect spinal cord neurons from oxidative stress. In the present study, primary spinal cord neurons of Sprague Dawley rats were cultured. Cell counting kit‑8 analysis was used to detect cytotoxicity of pterostilbene...
January 9, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29327381/oxidative-stress-impairs-myocyte-autophagy-resulting-in-myocyte-hypertrophy
#7
Jia-Pu Wang, Rui-Fang Chi, Ke Wang, Teng Ma, Xiao-Fei Guo, Xiao-Li Zhang, Bao Li, Fu-Zhong Qin, Xue-Bin Han, Bian-Ai Fan
Insufficient or excessive myocyte autophagy is associated with left ventricular (LV) hypertrophy. Reactive oxygen species mediate myocyte hypertrophy in vitro and pressure overload-induced LV hypertrophy in vivo. In the present study, we tested the hypothesis that oxidative stress induces autophagy impairment that results in myocyte hypertrophy. H9C2 cardiomyocytes were exposed to 10 and 50 μm hydrogen peroxide (H2 O2 ) for 48 h pretreated with autophagy inhibitor 3-methyladenine (3-MA). Male Sprague-Dawley rats underwent abdominal aortic constriction (AAC) or sham operation...
January 12, 2018: Experimental Physiology
https://www.readbyqxmd.com/read/29327342/reduced-lysosomal-clearance-of-autophagosomes-promotes-survival-and-colonization-of-helicobacter-pylori
#8
Lin Zhang, Wei Hu, Chi H Cho, Francis K L Chan, Jun Yu, J Ross Fitzgerald, Cynthia K Y Cheung, Zhan G Xiao, Jing Shen, Long F Li, Ming X Li, Justin C Y Wu, Thomas K W Ling, Jason Y K Chan, Ko Ho, Gary Tse, Siew C Ng, Sidney Yu, Maggie H T Wang, Tony Gin, Hassan Ashktorab, Duane T Smoot, Sunny H Wong, Matthew T V Chan, William K K Wu
Evasion of autophagy is key for intracellular survival of bacteria in host cells, but its involvement in persistent infection by Helicobacter pylori, a bacterium identified to invade gastric epithelial cells, remains obscure. The aim of this study was to functionally characterize the role of autophagy in H. pylori infection. Autophagy was assayed in H. pylori-infected human gastric epithelium and the functional role of autophagy was determined via genetic or pharmacologic ablation of autophagy in mouse and cell line models of H...
January 12, 2018: Journal of Pathology
https://www.readbyqxmd.com/read/29327301/lncrna-gas8-as1-inhibits-cell-proliferation-through-atg5-mediated-autophagy-in-papillary-thyroid-cancer
#9
Yuan Qin, Wei Sun, Hao Zhang, Ping Zhang, Zhihong Wang, Wenwu Dong, Liang He, Ting Zhang, Liang Shao, Wenqian Zhang, Changhao Wu
PURPOSE: The long non-coding RNA GAS8 antisense RNA 1 (lncRNA GAS8-AS1) is a tumor suppressor in papillary thyroid cancer (PTC), but the mechanisms underlying how GAS8-AS1 regulates PTC biology remain unclear. Here, we evaluated the molecular function of GAS8-AS1 in regulating autophagy in PTC cell lines. METHODS: GAS8-AS1 was overexpressed and knocked down in PTC cell lines by transfecting with expression plasmids or short interfering RNAs (siRNAs). Cell proliferation was evaluated using the Cell Counting Kit-8 (CCK-8)...
January 11, 2018: Endocrine
https://www.readbyqxmd.com/read/29325343/-expression-and-significance-of-autophagy-in-rabbit-model-of-tracheal-stenosis
#10
E Y Qin, L M Gan, J H Gan, Y Li, W T Li, C C Hou, X Y Meng, L Zhou, G N Liu
Objective: To investigate the expression and significance of autophagy in rabbit model of tracheal stenosis. Methods: A total of 18 rabbits were equally divided into 3 groups (blank control group, saline group, erythromycin group) in accordance with the random number table. After rabbit model of tracheal stenosis was established, no treatment was done with blank control group. Saline group was atomized with saline (0.54 mg/kg, 2 times/day), and erythromycin group was fed on erythromycin (7.5 mg/kg, 2 times/day) for 7 days before and 10 days after the operation...
December 26, 2017: Zhonghua Yi Xue za Zhi [Chinese medical journal]
https://www.readbyqxmd.com/read/29324976/ginsenoside-rg1-inhibits-apoptosis-by-increasing-autophagy-via-the-ampk-mtor-signaling-in-serum-deprivation-macrophages
#11
Ping Yang, Lu Ling, Wenjing Sun, Junquan Yang, Ling Zhang, Guoji Chang, Jiazhi Guo, Jun Sun, Lin Sun, Di Lu
Ginsenoside Rg1 (Rg1) has been widely used in a broad range of cardiovascular and cerebral-vascular diseases because of its unique therapeutic properties. However, the underlying mechanisms of Rg1 in the treatment of atherosclerosis have not been fully explored. This study sought to determine the precise molecular mechanisms on how Rg1 might be involved in regulating apoptosis in serum deprivation-induced Raw264.7 macrophages and primary bone marrow-derived macrophages. Results demonstrated that Rg1 treatment effectively suppressed apoptosis and the expression of phosphorylation level of mTOR induced by serum deprivation in Raw264...
January 9, 2018: Acta Biochimica et Biophysica Sinica
https://www.readbyqxmd.com/read/29321306/digitoxin-suppresses-human-cytomegalovirus-replication-via-na-k-atpase-%C3%AE-1-subunit-dependent-ampk-and-autophagy-activation
#12
Rupkatha Mukhopadhyay, Rajkumar Venkatadri, Jenny Katsnelson, Ravit Arav-Boger
Host-directed therapeutics for human cytomegalovirus (HCMV) requires elucidation of cellular mechanisms that inhibit HCMV. We report on a novel pathway used by cardiac glycosides to inhibit HCMV replication: induction of AMPK activity and autophagy flux through the Na+, K+/ATPase α1 subunit. Our data illustrate an intricate balance between autophagy regulators AMPK, mTOR and ULK1 during infection and treatment with the cardiac glycoside, digitoxin. Both infection and digitoxin induced AMPK phosphorylation, but ULK1 was differentially phosphorylated at unique sites leading to opposing effects on autophagy...
January 10, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29317426/the-wd40-domain-of-atg16l1-is-required-for-its%C3%A2-non-canonical-role-in-lipidation-of-lc3-at-single%C3%A2-membranes
#13
Katherine Fletcher, Rachel Ulferts, Elise Jacquin, Talitha Veith, Noor Gammoh, Julia M Arasteh, Ulrike Mayer, Simon R Carding, Thomas Wileman, Rupert Beale, Oliver Florey
A hallmark of macroautophagy is the covalent lipidation of LC3 and insertion into the double-membrane phagophore, which is driven by the ATG16L1/ATG5-ATG12 complex. In contrast, non-canonical autophagy is a pathway through which LC3 is lipidated and inserted into single membranes, particularly endolysosomal vacuoles during cell engulfment events such as LC3-associated phagocytosis. Factors controlling the targeting of ATG16L1 to phagophores are dispensable for non-canonical autophagy, for which the mechanism of ATG16L1 recruitment is unknown...
January 9, 2018: EMBO Journal
https://www.readbyqxmd.com/read/29316542/microrna-9a-5p-alleviates-ischemia-injury-after-focal-cerebral-ischemia-of-the-rat-by-targeting-atg5-mediated-autophagy
#14
Ning Wang, Lei Yang, Huixue Zhang, Xiaoyu Lu, Jianjian Wang, Yuze Cao, Lixia Chen, Xiaokun Wang, Lin Cong, Jie Li, Na Wang, Zhaojun Liu, Lihua Wang
BACKGROUND/AIMS: Previous studies have suggested that autophagy is activated in distinct cerebrovascular diseases, including stroke. However, the underlying regulatory mechanism of autophagy under stroke remained elusive. Accumulating evidence indicates that dysfunctions of microRNAs (miRNAs) are involved in the pathological process of stroke. Therefore, this study was taken to identify the effect of microRNA-9a-5p (miR-9a-5p) on autophagy in rats following stroke. METHODS: The rat model of focal cerebral ischemia was established by middle cerebral artery occlusion (MCAO) surgery; The neurological outcomes were defined by neurological evaluation and infarct volume; The western blotting and immunofluorescence assays were used to detected the protein levels of microtubule-associated protein 1 light chain 3 (LC3) and autophagy related 5 (ATG5); The mRNA level of miR-9a-5p, LC3 and ATG5 were quantified by real-time RT-PCR; The luciferase activities of ATG5 and miR-9a-5p was detected by luciferase assay...
December 22, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29316373/tanshinone-iia-induces-cell-death-via-beclin-1-dependent-autophagy-in-oral-squamous-cell-carcinoma-scc-9-cell-line
#15
Ye Qiu, Conghua Li, Qinhua Wang, Xingqi Zeng, Ping Ji
Tanshinone IIA (TAN) is one of the major functional compounds of Salvia miltiorrhiza Bunge and possesses the ability to suppress the growth of multiple cancer cell types via its apoptosis- and autophagy-inducing functions. In this study, the effect of TAN therapy on the survival of oral squamous cell carcinoma (OSCC) was evaluated, and the underlying mechanism involved in the treatment was investigated. Human oral squamous cell carcinoma cell SCC-9 was used for in vitro assays and induction in an OSCC xenograft mouse model...
January 6, 2018: Cancer Medicine
https://www.readbyqxmd.com/read/29315230/maternal-high-fructose-intake-increases-the-vulnerability-to-post-weaning-high-fat-diet-induced-programmed-hypertension-in-male-offspring
#16
You-Lin Tain, Wei-Chia Lee, Kay L H Wu, Steve Leu, Julie Y H Chan
Widespread consumption of high-fructose and high-fat diets relates to the global epidemic of hypertension. Hypertension may originate from early life by a combination of prenatal and postnatal nutritional insults. We examined whether maternal high-fructose diet increases vulnerability to post-weaning high-fructose or high-fat diets induced hypertension in adult offspring and determined the underlying mechanisms. Pregnant Sprague-Dawley rats received regular chow (ND) or chow supplemented with 60% fructose (HFR) during the entire pregnancy and lactation periods...
January 9, 2018: Nutrients
https://www.readbyqxmd.com/read/29306553/knockout-of-autophagy-gene-atg5-in-mice-vaginal-cells-abrogates-cytokine-response-and-pathogen-clearance-during-vaginal-infection-of-candida-albicans
#17
Ankit Shroff, Roicy Sequeira, Vainav Patel, K V R Reddy
The female reproductive tract (FRT) presents a unique challenge to the mucosal immune system as it needs to monitor constantly for the presence of opportunistic pathogens amidst its commensal flora. During infection, autophagy plays a critical role in pathogen clearance, presentation of antigens and production of pro-inflammatory cytokines. However, no information is available that describes the role of autophagy in mouse vaginal infection of Candida albicans. The objective of our study is to evaluate the effect of autophagy gene, ATG5 knockout in vaginal cells in response to vaginal C...
December 28, 2017: Cellular Immunology
https://www.readbyqxmd.com/read/29306208/alpha-2-dihydroxy-4-4-dimethoxydihydrochalcone-inhibits-cell-proliferation-invasion-and-migration-in-gastric-cancer-in-part-via-autophagy
#18
Boshun Wan, Junqiu Zhu, Qing Chang, Haihua Zhou, Zhan Shi, Li Min, YueJiao Cai, Honggeng Guan
Gastric cancer is a leading cause of mortality worldwide. Alpha, 2'-dihydroxy-4,4'-dimethoxydihydrochalcone is a type of limonoid mainly isolated from Cedrela odorata (Meliaceae) that has been shown to suppress cell proliferation in several human carcinoma cell lines. In this study, we investigated the anti-cancer ability of alpha, 2'-dihydroxy-4,4'-dimethoxydihydrochalcone and its underlying mechanism in MKN45 cells. Alpha, 2'-dihydroxy-4,4'-dimethoxydihydrochalcone induced excess reactive oxygen species (ROS) accumulation...
January 2, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29301683/autophagy-involved-in-the-activation-of-the-nrf2-antioxidant-system-in-testes-of-heat-exposed-mice
#19
Zhaojian Li, Yansen Li, Xin Zhou, Pengyuan Dai, Chunmei Li
Hyperthermia causes oxidative stress in testes, which triggers antioxidant signals including autophagy and nuclear factor erythroid 2-related factor 2 (Nrf2). However, their relationship in testes under oxidative stress is unclear. In this study, we conducted testes injection for autophagy alteration and heat exposure to reveal the interaction between autophagy and the Nrf2-antioxidant system. Male mice were injected once with normal saline as control (Cont group), autophagy inhibitor 3-methyladenine (3-MA group) or autophagy inducer rapamycin (Rapa group)...
January 2018: Journal of Thermal Biology
https://www.readbyqxmd.com/read/29289836/brevilin-a-induces-apoptosis-and-autophagy-of-colon-adenocarcinoma-cell-ct26-via-mitochondrial-pathway-and-pi3k-akt-mtor-inactivation
#20
Pengtao You, Hezhen Wu, Meng Deng, Jingling Peng, Fangping Li, Yanfang Yang
Brevilin A is a sesquiterpene lactone isolated from Centipeda minima and possesses inhibitory effects on proliferation of various tumor cells. In this study, Brevilin A inhibitory effect on proliferation and its molecular mechanism of action were investigated both in vivo and in vitro in colon adenocarcinoma CT26 cells. The results indicated that the inhibitory effect of Brevilin A in CT26 proliferation was dose-dependent and this effect was due to apoptosis. Furthermore, Brevilin A increased ROS levels, decreased mitochondrial membrane potential (MMP) and induced apoptosis of CT26 cell in a dose-dependent manner...
December 28, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
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