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Autophagy

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https://www.readbyqxmd.com/read/28651421/-effects-of-change-in-the-activity-of-vacuolar-adenosine-triphosphatase-of-myocardial-lysosome-on-myocardial-damage-in-rats-after-severe-burn-and-its-mechanism
#1
X P Yan, D X Zhang, T T Yan, Q Zhang, J Z Jia, Y S Huang
Objective: To explore the effects of change of activity of vacuolar adenosine triphosphatase (V-ATPase) of myocardial lysosome on myocardial damage in rats after severe burn and its mechanism. Methods: The myocardial lysosomes were extracted from the hearts of 12 SD rats with ultra-high speed gradient density centrifugation, then Western blotting and transmission electron microscope observation were conducted for identification. One hundred and twenty rats were divided into pure burn group, ATP group, normal control group, and bafilomycin group according to the random number table, with 30 rats in each group...
May 20, 2017: Zhonghua Shao Shang za Zhi, Zhonghua Shaoshang Zazhi, Chinese Journal of Burns
https://www.readbyqxmd.com/read/28651114/isolation-and-functional-interrogation-of-adult-human-prostate-epithelial-stem-cells-at-single-cell-resolution
#2
Wen-Yang Hu, Dan-Ping Hu, Lishi Xie, Ye Li, Shyama Majumdar, Larisa Nonn, Hong Hu, Toshi Shioda, Gail S Prins
Using primary cultures of normal human prostate epithelial cells, we developed a novel prostasphere-based, label-retention assay that permits identification and isolation of stem cells at a single cell level. Their bona fide stem cell nature was corroborated using in vitro and in vivo regenerative assays and documentation of symmetric/asymmetric division. Robust WNT10B and KRT13 levels without E-cadherin or KRT14 staining distinguished individual stem cells from daughter progenitors in spheroids. Following FACS to isolate label-retaining stem cells from label-free progenitors, RNA-seq identified unique gene signatures for the separate populations which may serve as useful biomarkers...
June 16, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28651104/autophagy-is-an-important-event-for-low-dose-cytarabine-treatment-in-acute-myeloid-leukemia-cells
#3
Liyun Chen, Pei Guo, Yunxiang Zhang, Xiaoyang Li, Peimin Jia, Jianhua Tong, Junmin Li
Cytarabine (Ara-c) has been an important agent in acute myeloid leukemia (AML) treatment for more than 40 years. While, the mechanisms underlying low dose cytarabine (LD Ara-c) is poorly understood. In this study, we investigated the therapeutic effect of LD Ara-C in vitro. U937 and HEL cell lines were treated with increasing dose of Ara-C and showed growth inhibition rates in a time and dose-dependent manner. Treatment with LD Ara-C (50nM) induced a time-dependent increase in expression of microtubule-associated protein light chain 3 (LC3) and beclin1, but degradation of sequestosome1 (p62) in both U937 and HEL cells...
June 16, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28650983/differential-induction-of-apoptosis-and-autophagy-by-pyrrolizidine-alkaloid-clivorine-in-human-hepatoma-huh-7-5-cells-and-its-toxic-implication
#4
Wenju Liu, Xu Li, Bo Zhou, Shoucai Fang, Wenzhe Ho, Hui Chen, Hao Liang, Li Ye, Jun Tang
Growing evidence suggests that the pyrrolizidine alkaloids (PAs)-induced hepatotoxicity is mediated by multiple cell death/defence modalities. However, the detailed mechanisms are still lacking. In this study, the hepatotoxic effects of four PAs including three retronecine-type ones (senecionine, seneciphylline and monocrotaline) and one otonecine-type (clivorine) on the proliferation of Huh-7.5 cells and the possible mechanisms were investigated. The results showed that all the PAs could inhibit cell proliferation and induce apoptosis in a concentration-dependent manner...
2017: PloS One
https://www.readbyqxmd.com/read/28650718/subversion-of-rab5-regulated-autophagy-by-the-intracellular-pathogen-ehrlichia-chaffeensis
#5
Yasuko Rikihisa
Intracellular pathogens often exploit RAB functions to establish a safe haven in which to survive and proliferate. Ehrlichia chaffeensis, an obligatory intracellular bacterium, resides in specialized membrane-bound inclusions that have early endosome-like characteristics, e.g., resident RAB5 GTPase and RAB5 effectors, including VPS34 (the catalytic subunit of class III phosphatidylinositol 3-kinase), but the inclusions lack late endosomal or lysosomal markers. Within inclusions, Ehrlichia obtains host-derived nutrients by inducing RAB5-regulated autophagy using Ehrlichia translocated factor-1 deployed by its type IV secretion system...
June 26, 2017: Small GTPases
https://www.readbyqxmd.com/read/28650662/glucose-restriction-combined-with-autophagy-inhibition-and-chemotherapy-in-hct-116-spheroids-decreases-cell-clonogenicity-and-viability-regulated-by-tumor-suppressor-genes
#6
Monica M Schroll, Gabriel J LaBonia, Katelyn R Ludwig, Amanda B Hummon
Drug resistance is a prevalent phenomenon that decreases the efficacy of cancer treatments and contributes to cancer progression and metastasis. Weakening drug resistant cancer cells prior to chemotherapy is a potential strategy to combat chemoresistance. One approach to damage resistant cancer cells is modulation of nutritional intake. The combination of nutrient restriction with targeted compound treatment results in pronounced molecular changes. This study provides valuable information about augmenting existing chemotherapeutic regimes with simultaneous glucose restriction and autophagy inhibition in colorectal cancer cells...
June 26, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28650490/hypoxia-induced-tumor-cell-resistance-is-overcome-by-synergistic-gapdh-sirna-and-chemotherapy-co-delivered-by-long-circulating-and-cationic-interior-liposomes
#7
Jibin Guan, Jin Sun, Feilong Sun, Bo Lou, Dong Zhang, Vida Mashayekhi, Negar Sadeghi, Gert Storm, Enrico Mastrobattista, Zhonggui He
Chemotherapeutic drug resistance of tumor cells under hypoxic conditions is caused by the inhibition of apoptosis by autophagy and drug efflux via adenosine triphosphate (ATP)-dependent transporter activation, among other factors. Here, we demonstrate that disrupting glyceraldehyde-3-phosphate dehydrogenase (GAPDH) expression can reduce the autophagy and ATP levels in tumor cells. To test whether GAPDH knockdown is sufficient to overcome drug resistance, a nanocarrier (asymmetry-membrane liposome) was designed to encapsulate GAPDH-siRNA with a low dose of paclitaxel (PTX)...
June 26, 2017: Nanoscale
https://www.readbyqxmd.com/read/28650265/autophagy-regulates-dna-repair-through-sqstm1-p62
#8
Yuchen Feng, Daniel J Klionsky
Macroautophagy/autophagy is primarily a degradative pathway that clears malfunctioning cellular components in response to various types of stress. Recent studies have indicated that autophagy also plays an important role in maintaining genome stability. Loss of autophagy is associated with increased damage to DNA, inappropriate amplification of genomic regions and abnormal chromosome number. In a recent paper by Wang et al. the authors uncover a mechanism through which autophagy regulates the ubiquitination of chromatin...
June 3, 2017: Autophagy
https://www.readbyqxmd.com/read/28648608/structures-of-pgam5-provide-insight-into-active-site-plasticity-and-multimeric-assembly
#9
Apirat Chaikuad, Panagis Filippakopoulos, Sean R Marcsisin, Sarah Picaud, Martin Schröder, Shiori Sekine, Hidenori Ichijo, John R Engen, Kohsuke Takeda, Stefan Knapp
PGAM5 is a mitochondrial membrane protein that functions as an atypical Ser/Thr phosphatase and is a regulator of oxidative stress response, necroptosis, and autophagy. Here we present several crystal structures of PGAM5 including the activating N-terminal regulatory sequences, providing a model for structural plasticity, dimerization of the catalytic domain, and the assembly into an enzymatically active dodecameric form. Oligomeric states observed in structures were supported by hydrogen exchange mass spectrometry, size-exclusion chromatography, and analytical ultracentrifugation experiments in solution...
June 10, 2017: Structure
https://www.readbyqxmd.com/read/28648601/inhibition-of-pld1-activity-causes-er-stress-via-regulation-of-copii-vesicle-formation
#10
Hiroshi Nakagawa, Kazuki Hazama, Katsumasa Ishida, Masayuki Komori, Kazuhiko Nishimura, Saburou Matsuo
Phospholipase D (PLD) plays a crucial role in the regulation of some cellular processes, including autophagy and apoptosis. Accumulation of protein in the endoplasmic reticulum (ER) lumen causes ER stress. Although ER stress is a principal cause of apoptosis and autophagy, the relationship between PLD activity and ER stress remains unclear. Protein transport from the ER to the Golgi apparatus is conducted by coat complex II (COPII) transport vesicles. Here, we demonstrated that inhibition of PLD1 activity or PLD1 knockdown suppressed COPII vesicle transport in normal rat kidney (NRK) cells...
June 22, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28648145/er-membrane-protein-complex-subunit-6-emc6-is-a-novel-tumor-suppressor-in-gastric-cancer
#11
Xiaokun Wang, Yan Xia, Chentong Xu, Xin Lin, Peng Xue, Shijie Zhu, Yun Bai, Yingyu Chen
Endoplasmic reticulum (ER) membrane protein complex subunit 6 (EMC6) is a novel human autophagy-related molecule. Here, using tissue microarray and immunohistochemistry, we report that EMC6 protein is lost or reduced in glandular cells of patients with gastric adenocarcinoma, compared to normal stomach mucosa. Overexpression of EMC6 in gastric cancer cells inhibited cell growth, migration, and invasion, and induced apoptosis and cell cycle arrest at S-phase. Further investigation suggested that EMC6 overexpression in BGC823 cells reduced tumorigenicity in a xenograft model, demonstrating that EMC6 has the characteristics of a tumor suppressor...
June 26, 2017: BMB Reports
https://www.readbyqxmd.com/read/28647906/exogenous-gdf11-induces-cardiac-and-skeletal-muscle-dysfunction-and-wasting
#12
Teresa A Zimmers, Yanling Jiang, Meijing Wang, Tiffany W Liang, Joseph E Rupert, Ernie D Au, Francesco E Marino, Marion E Couch, Leonidas G Koniaris
Growth differentiation factor 11 (GDF11), a TGF-beta superfamily member, is highly homologous to myostatin and essential for embryonic patterning and organogenesis. Reports of GDF11 effects on adult tissues are conflicting, with some describing anti-aging and pro-regenerative activities on the heart and skeletal muscle while others opposite or no effects. Herein, we sought to determine the in vivo cardiac and skeletal muscle effects of excess GDF11. Mice were injected with GDF11 secreting cells, an identical model to that used to initially identify the in vivo effects of myostatin...
July 2017: Basic Research in Cardiology
https://www.readbyqxmd.com/read/28647611/autophagy-suppresses-isoprenaline-induced-m2-macrophage-polarization-via-the-ros-erk-and-mtor-signaling-pathway
#13
Meihua Shan, Junfang Qin, Fengjiao Jin, Xiao Han, Haitao Guan, Xiaoge Li, Jiahui Zhang, Hongyao Zhang, Yue Wang
The objective of this study was to examine the effect of autophagy on stress-induced M2 macrophage polarization in the tumor microenvironment of breast cancer and to determine whether the underlying mechanism was related to the reactive oxygen species (ROS)/ERK and mTOR pathway. In vitro, we found that the basal autophagy level in mouse RAW 264.7 macrophages decreased with the incubation of tumor cell culture supernatant. Similarly, the polarization of RAW 264.7 to M2 macrophages was inhibited by the autophagy inducer rapamycin and increased by the autophagy inhibitor 3-MA or by siBeclin1...
June 21, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28647372/delta-opioid-receptor-agonist-attenuates-lipopolysaccharide-induced-myocardial-injury-by-regulating-autophagy
#14
Pin Zhao, Jianke Kuai, Jinjian Gao, Li Sun, Yan Wang, Linong Yao
BACKGROUND: Previous studies have described the protective effects of DADLE on myocardial injury in sepsis. Recently, autophagy has been shown to be an innate defense mechanism in sepsis-related myocardial injury. However, whether DADLE has an pro-autophagic effect is yet to be elucidated. The present study aimed to investigate the effect of DADLE on the regulation of autophagy during sepsis. METHODS: Male mice were subjected to LPS or vehicle intraperitoneal injection...
June 21, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28647359/mild-hypothermia-ameliorates-muscle-wasting-in-septic-rats-associated-with-hypothalamic-ampk-induced-autophagy-and-neuropeptides
#15
Chun Cao, Tao Gao, Minhua Cheng, Fengchan Xi, Chenyan Zhao, Wenkui Yu
Sepsis, always developing muscle wasting, contributes to serious complications and mortality. Mild hypothermia has been reported to have protective effects on the prognosis of septic patients. However, the underlying mechanisms remain unclear. We therefore hypothesized that mild hypothermia could ameliorate muscle wasting during sepsis and whether it was associated with hypothalamus AMPK-induced autophagy and neuropeptides. Adult male Sprague-Dawley rats were intraperitoneally injected with lipopolysaccharide (LPS) (5 mg/kg) or saline...
June 21, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28647341/suppression-of-autophagic-flux-contributes-to-cardiomyocyte-death-by-activation-of-necroptotic-pathways
#16
Makoto Ogasawara, Toshiyuki Yano, Masaya Tanno, Koki Abe, Satoko Ishikawa, Takayuki Miki, Atsushi Kuno, Toshiyuki Tobisawa, Shingo Muratsubaki, Kouhei Ohno, Yuki Tatekoshi, Kei Nakata, Wataru Ohwada, Tetsuji Miura
BACKGROUND: The role of necroptosis in myocardial injury has not been fully characterized. Here we examined roles of mitochondrial permeability transition pore (mPTP) and autophagy in necroptosis of cardiomyocytes. METHODS AND RESULTS: In H9c2 cells, necroptosis was induced by treatment with TNF-α (TNF) and z-VAD-fmk (zVAD) for 24h, and necroptotic death was determined by LDH release (as % of total). TNF/zVAD increased LDH release from 16.6±4.3% to 60.6±2.7%, and the LDH release was suppressed by necrostatin-1 (29...
June 21, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28647273/the-effect-of-mir-30d-on-apoptosis-and-autophagy-in-cultured-astrocytes-under-oxygen-glucose-deprivation
#17
Fengyan Zhao, Yi Qu, Huiqing Wang, Lan Huang, Jianghu Zhu, Shiping Li, Yu Tong, Li Zhang, Jiao Li, Dezhi Mu
MiR-30d has been demonstrated to regulate autophagy in human cancer cells. However, the role of miR-30d in astrocytes exposed to hypoxia-ischemia is not clear. In this study, we established model of oxygen and glucose deprivation (OGD) with rat primary astrocytes and evaluated the role of miR-30d in the cross-talk between autophagy and apoptosis in astrocytes after OGD. We found that miR-30d inhibited Beclin1 expression in astrocytes. Inhibition of miR-30d by antagomir significantly increased cell autophagy but decreased cell apoptosis in astrocytes exposed to OGD...
June 21, 2017: Brain Research
https://www.readbyqxmd.com/read/28646911/autophagy-and-multidrug-resistance-in-cancer
#18
REVIEW
Ying-Jie Li, Yu-He Lei, Nan Yao, Chen-Ran Wang, Nan Hu, Wen-Cai Ye, Dong-Mei Zhang, Zhe-Sheng Chen
Multidrug resistance (MDR) occurs frequently after long-term chemotherapy, resulting in refractory cancer and tumor recurrence. Therefore, combatting MDR is an important issue. Autophagy, a self-degradative system, universally arises during the treatment of sensitive and MDR cancer. Autophagy can be a double-edged sword for MDR tumors: it participates in the development of MDR and protects cancer cells from chemotherapeutics but can also kill MDR cancer cells in which apoptosis pathways are inactive. Autophagy induced by anticancer drugs could also activate apoptosis signaling pathways in MDR cells, facilitating MDR reversal...
June 24, 2017: Chinese Journal of Cancer
https://www.readbyqxmd.com/read/28646601/autophagy-activation-is-required-for-myofibroblasts-differentiation-during-healing-of-oral-mucosa
#19
Enrica Vescarelli, Andrea Pilloni, Francesco Dominici, Paola Pontecorvi, Antonio Angeloni, Antonella Polimeni, Simona Ceccarelli, Cinzia Marchese
AIM: It is known that periodontal tissues heal faster that skin, and gingiva in particular heal without scar formation. The mechanisms regulating this behavior are still unclear. The aim of our work is to compare wound healing in oral mucosa and gingiva, investigating the role of αSMA-expressing myofibroblasts and autophagy. MATERIALS AND METHODS: Biopsies were obtained from 7 patients immediately before and 24h after vertical releasing incision in oral mucosa and attached gingiva...
June 24, 2017: Journal of Clinical Periodontology
https://www.readbyqxmd.com/read/28646367/ifn%C3%AE-producing-cd4-t-lymphocytes-the-double-edged-swords-in-tuberculosis
#20
Pawan Kumar
IFNγ-producing CD4(+) T cells (IFNγ(+)CD4(+) T cells) are the key orchestrators of protective immunity against Mycobacterium tuberculosis (Mtb). Primarily, these cells act by enabling Mtb-infected macrophages to enforce phagosome-lysosome fusion, produce reactive nitrogen intermediates (RNIs), and activate autophagy pathways. However, TB is a heterogeneous disease and a host of clinical and experimental findings has also implicated IFNγ(+)CD4(+) T cells in TB pathogenesis. High frequency of IFNγ(+)CD4(+) T cells is the most invariable feature of the active disease...
December 2017: Clinical and Translational Medicine
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