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Beclin1

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https://www.readbyqxmd.com/read/28100346/-impact-of-cd137-cd137l-signaling-mediated-exocytosis-of-autophagosome-within-vascular-smooth-muscle-cells-on-the-formation-of-atherosclerotic-calcification
#1
B Li, X Y Li, W Zhong, C Shao, Z Q Wang, W Yuan, J C Yan
Objective: To explore whether CD137-CD137L signaling mediated exocytosis of autophagosome within vascular smooth muscle cells (VSMCs) could influence the formation of atherosclerotic calcification. Methods: Fifteen 8-week-old male ApoE(-/-)(C57BL/6J-KO) mice fed with high fat diet for 5 weeks were randomly divided into three groups by using stochastic indicator method as follows: control group, n=5; agonist-CD137 group: agonist-CD137 antibody 200 μg/2 weeks for 4 weeks, ip, n=5; anti-CD137 group: 200 μg anti-CD137 antibody+ 200 μg agonist-CD137 antibody/2 weeks for 4 weeks, ip, n=5...
January 25, 2017: Zhonghua Xin Xue Guan Bing za Zhi
https://www.readbyqxmd.com/read/28088782/pde5-inhibitors-enhance-the-lethality-of-pemetrexed-sorafenib
#2
Laurence Booth, Jane L Roberts, Andrew Poklepovic, Paul Dent
The combination of pemetrexed and sorafenib has significant clinical activity against a wide variety of tumor types in patients and the present studies were performed to determine whether sildenafil enhances the killing potential of [pemetrexed + sorafenib]. In multiple genetically diverse lung cancer cell lines, sildenafil enhanced the lethality of [pemetrexed + sorafenib]. The three-drug combination reduced the activities of AKT, mTOR and STAT transcription factors; increased the activities of eIF2α and ULK-1; lowered the expression of MCL-1, BCL-XL, thioredoxin and SOD2; and increased the expression of Beclin1...
January 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28075440/the-metastasis-suppressor-gene-kiss-1-regulates-osteosarcoma-apoptosis-and-autophagy-processes
#3
Yiran Yin, Lian Tang, Lei Shi
The expression of the metastasis suppressor gene KISS-1 in osteosarcoma cells during apoptosis and autophagy was evaluated. MG-63 osteosarcoma cells were transfected with either KISS-1 overexpression or KISS-1 knockdown expression vector in vitro, and compared with cell lines transfected with empty vector. After 12, 24, 48 and 72 h of cell culture, the cell proliferation was examined. The MTT method was used to detect apoptosis by flow cytometry, and the mRNA levels of apoptosis and autophagy markers caspase-3, Bcl-2, Bax, LC3 and Beclin1 were assessed by RT-PCR...
January 11, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28061438/combination-of-arsenic-trioxide-and-everolimus-rad001-synergistically-induces-both-autophagy-and-apoptosis-in-prostate-cancer-cells
#4
Sheng Tai, Lingfan Xu, Ming Xu, Ligang Zhang, Yangyang Zhang, Kaipin Zhang, Li Zhang, Chaozhao Liang
The inhibitor of PI3K-AKT-mTOR pathway, such as Rad001, has not shown therapeutic efficacy as a single agent in prostate cancer. Arsenic trioxide induces the autophagic pathway in prostate cancer cells. We identified Arsenic trioxide can synergize with Rad001 to induce cytotoxicity of prostate cancer cells. Moreover, we identified synergistic induction of autophagy and apoptosis as the underlying mechanism. This enhanced autophagic cell death is accompanied by increased Beclin1 mRNA stability as well as upregulation of ATG5-ATG12 conjugate, Beclin1, and LC3-2...
January 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28059052/gastrin-enhances-autophagy-and-promotes-gastric-carcinoma-proliferation-via-inducing-ampk%C3%AE
#5
Zhuang Kun, Guo Hanqing, Tang Hailing, Yan Yuan, Zhang Jun, Zhang Lingxia, Han Kun, Zhang Xin
Gastric cancer (GC) is one of the most frequent epithelial malignancies worldwide. The gastrointestinal (GI) peptide gastrin is an important regulator of the secretion and release of gastric acid from stomach parietal cells and it also plays a vital role in the development and progression of gastric cancer. The aim of the current study was to investigate the role and underlying mechanism of gastrin and autophagy in regulating gastric cancer tumorigenesis. Gastrin-17 amide (G-17) was applied in the gastric cancer cell lines SGC7901 and MGC-803...
January 5, 2017: Oncology Research
https://www.readbyqxmd.com/read/28053206/gsk3b-mediated-phosphorylation-of-mcl1-regulates-axonal-autophagy-to-promote-wallerian-degeneration
#6
Shuji Wakatsuki, Shinji Tokunaga, Megumi Shibata, Toshiyuki Araki
Macroautophagy is a catabolic process, in which portions of cytoplasm or organelles are delivered to lysosomes for degradation. Emerging evidence has indicated a pathological connection between axonal degeneration and autophagy. However, the physiological function and induction mechanism of autophagy in axons remain elusive. We herein show that, through activation of BECLIN1, glycogen synthase kinase 3B (GSK3B)-mediated phosphorylation of BCL2 family member MCL1 induces axonal autophagy and axonal degeneration...
January 4, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28043814/autophagy-induction-reduces-telomerase-activity-in-hela-cells
#7
Fatemeh Taji, Homa Mohseni Kouchesfahani, Farzaneh Sheikholeslami, Bizhan Romani, Kazem Baesi, Rouhollah Vahabpour, Mahdi Edalati, Ladan Teimoori-Toolabi, Ehsan Ollah Jazaeri, Asghar Abdoli
Autophagy is a cellular homeostatic process whereby damaged proteins and organelles are encapsulated into double membrane vesicles, called autophagosomes, for lysosomal digestion. Beclin1 plays a key role in the initial steps of autophagosome formation. In this study, we evaluated the effect of Beclin 1 overexpression in induction of autophagy and the relationship between autophagy induction and telomerase activity in HeLa cells. We found that overexpression of Beclin 1 in HeLa cells leads to autophagosome formation as shown by intracellular autophagosomal marker LC3-II staining...
December 30, 2016: Mechanisms of Ageing and Development
https://www.readbyqxmd.com/read/27999666/beclin-1-mediated-autophagy-may-be-involved-in-the-elderly-cognitive-and-affective-disorders-in-streptozotocin-induced-diabetic-mice
#8
Zhu-Fei Guan, Xiu-Ling Zhou, Xiao-Ming Zhang, Yu Zhang, Yan-Mei Wang, Qi-Lin Guo, Gang Ji, Guo-Feng Wu, Na-Na Wang, Hao Yang, Zhong-Yu Yu, Hou-Guang Zhou, Jing-Chun Guo, Ying-Chao Liu
BACKGROUND: Diabetes is the most common metabolic disease with many chronic complications, and cognitive disorders are one of the common complications in patients with diabetes. Previous studies have showed that autophagy played important roles in the progression of metabolic syndrome, diabetes and other diseases. So we investigated whether aged diabetic mice are prone to be associated with the cognitive and affective disorders and whether Beclin-1-mediated autophagy might be involved in thepahological process...
2016: Translational Neurodegeneration
https://www.readbyqxmd.com/read/27998869/-role-of-autophagy-in-fasudil-induced-rho-kinase-inhibition-for-protection-against-myocardial-ischemia-reperfusion-injury-in-rats
#9
Hong-Wei Ye, Ting-Ting Fang, Xiao-Yu Gu, Ya Wang, Guang-Yu Zhu, Ying Yu, Qin Gao
OBJECTIVE: To investigate the changes of autophagy in ischemic myocardium of rats treated with fasudil for inhibiting Rho kinase. METHODS: The hearts isolated from male Sprague-Dawley rats were subjected to 30 min of occlusion of the left anterior descending artery followed by 120 min of reperfusion with or without treatment with fasudil or fasudil+Wort. The left ventricular hemodynamics were continuously recorded, and the coronary effluent was collected during the reperfusion to determine lactate dehydrogenase (LDH) levels...
December 20, 2016: Nan Fang Yi Ke da Xue Xue Bao, Journal of Southern Medical University
https://www.readbyqxmd.com/read/27994061/focal-adhesion-kinase-mediated-phosphorylation-of-beclin1-suppresses-cardiomyocyte-autophagy-and-initiates-hypertrophic-growth
#10
Zhaokang Cheng, Qiang Zhu, Rachel Dee, Zachary Opheim, Christopher P Mack, Douglas M Cyr, Joan M Taylor
Autophagy is an evolutionarily conserved intracellular degradation/recycling system that is essential for cellular homeostasis but is dysregulated in a number of diseases including myocardial hypertrophy. While it is clear that limiting or accelerating autophagic flux can result in pathological cardiac remodeling, the physiological signaling pathways that fine-tune cardiac autophagy are poorly understood. Herein, we demonstrated that stimulation of cardiomyocytes with phenylephrine (PE), a well-known hypertrophic agonist, suppresses autophagy and that activation of focal adhesion kinase (FAK) is necessary for PE-stimulated autophagy suppression and subsequent initiation of hypertrophic growth...
December 19, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27973739/phosphatidylinositol-3-phosphate-in-the-regulation-of-autophagy-membrane-dynamics
#11
REVIEW
Anna Chiara Nascimbeni, Patrice Codogno, Etienne Morel
Phosphatidylinositol-3-phosphate (PI3P) is a key player in membrane dynamics and trafficking regulation. Most PI3P is associated with endosomal membranes and with the autophagosome pre-assembly machinery, presumably at the endoplasmic reticulum. The enzyme responsible for most PI3P synthesis, VPS34, and proteins such as Beclin1 and ATG14L that regulate PI3P levels are positive modulators of autophagy initiation. It had been assumed that a local PI3P pool was present at autophagosomes and pre-autophagosomal structures, such as the omegasome and the phagophore...
December 14, 2016: FEBS Journal
https://www.readbyqxmd.com/read/27916732/ghrelin-improves-vascular-autophagy-in-rats-with-vascular-calcification
#12
Mingming Xu, Lin Liu, Chenfang Song, Wei Chen, Shuyan Gui
BACKGROUNDS: This study aimed to investigate whether ghrelin ameliorated vascular calcification (VC) through improving autophagy. METHODS: VC model was induced by nicotine plus vitamin D3 in rats and β-glycerophosphate in vascular smooth muscle cell (VSMC). Calcium deposition was detected by von Kossa staining or alizarin red S staining. ALP activity was also detected. Western blot was used to assess the protein expression. RESULTS: Ghrelin treatment attenuated the elevation of calcium deposition and ALP activity in VC model both in vivo and in vitro...
December 1, 2016: Life Sciences
https://www.readbyqxmd.com/read/27904666/ad-hgf-improves-the-cardiac-remodeling-of-rat-following-myocardial-infarction-by-upregulating-autophagy-and-necroptosis-and-inhibiting-apoptosis
#13
Jiabao Liu, Peng Wu, Yunle Wang, Yingqiang Du, Nan A, Shuiyuan Liu, Yiming Zhang, Ningtian Zhou, Zhihui Xu, Zhijian Yang
Cell death in MI is the most critical determinant of subsequent left ventricular remodeling and heart failure. Besides apoptosis, autophagy and necroptosis have been recently found to be another two regulated cell death styles. HGF has been reported to have a protective role in MI, but its impact on the three death styles remains unclear. Thus, our study was performed to investigate the distribution of autophagy, apoptosis and necroptosis in cardiac tissues after MI and explore the role and mechanism of Ad-HGF on cardiac remodeling by regulating the three death styles...
2016: American Journal of Translational Research
https://www.readbyqxmd.com/read/27903966/pde5-inhibitors-enhance-the-lethality-of-pemetrexed-through-inhibition-of-multiple-chaperone-proteins-and-via-the-actions-of-cyclic-gmp-and-nitric-oxide
#14
Laurence Booth, Jane L Roberts, Andrew Poklepovic, Sarah Gordon, Paul Dent
Phosphodiesterase 5 (PDE5) inhibitors prevent the breakdown of cGMP that results in prolonged protein kinase G activation and the generation of nitric oxide. PDE5 inhibitors enhanced the anti-NSCLC cell effects of the NSCLC therapeutic pemetrexed. [Pemetrexed + sildenafil] activated an eIF2α - ATF4 - CHOP - Beclin1 pathway causing formation of toxic autophagosomes; activated a protective IRE1 - XBP-1 - chaperone induction pathway; and activated a toxic eIF2α - CHOP - DR4 / DR5 / CD95 induction pathway. [Pemetrexed + sildenafil] reduced the expression of c-FLIP-s, MCL-1 and BCL-XL that was blocked in a cell-type -dependent fashion by either over-expression of HSP90 / GRP78 / HSP70 / HSP27 or by blockade of eIF2α-CHOP signaling...
November 26, 2016: Oncotarget
https://www.readbyqxmd.com/read/27895792/microrna-199a-5p-inhibits-cisplatin-induced-drug-resistance-via-inhibition-of-autophagy-in-osteosarcoma-cells
#15
Yusheng Li, Wei Jiang, Yuling Hu, Zixun Da, Chao Zeng, Min Tu, Zhenhan Deng, Wenfeng Xiao
Osteosarcoma (OS) is the most common cancer of the bone. Chemotherapy is commonly used for the clinical treatment of OS. However, chemoresistance to cisplatin [also known as diamminedichloridoplatinum (II) (DDP)] is a major obstacle for OS therapy, the underlying mechanism of which is not fully understood. The present study aimed to investigate the role of microRNA (miR)-199a-5p in the regulation of chemoresistance to DDP in OS cells. Reverse transcription-quantitative polymerase chain reaction demonstrated that the expression level of miR-199a-5p was significantly reduced in human OS MG63 cells...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27882565/tanshinone-iia-attenuates-a%C3%AE-25-35-induced-spatial-memory-impairment-via-upregulating-receptors-for-activated-c-kinase1-and-inhibiting-autophagy-in-hippocampus
#16
Jiejun Zhu, Shiping Liao, Liming Zhou, Lihong Wan
OBJECTIVES: Tanshinone IIA (Tan IIA) may exert significant protective effects against the neurotoxicity induced by β-amyloid protein (Aβ). This study was designed to investigate the possible neuroprotective mechanism of Tan IIA on Aβ25-35 -induced spatial memory impairment in mice. METHODS: After 3 weeks of preventive treatment (Tan IIA or oil), all male Kunming mice were subjected to Aβ25-35 (10 μl, intracerebroventricularly (i.c.v.)) to establish the spatial memory impairment model...
February 2017: Journal of Pharmacy and Pharmacology
https://www.readbyqxmd.com/read/27877136/novel-role-of-er-stress-and-autophagy-in-microcystin-lr-induced-apoptosis-in-chinese-hamster-ovary-cells
#17
Shenshen Zhang, Chuanrui Liu, Yang Li, Mustapha U Imam, Hui Huang, Haohao Liu, Yongjuan Xin, Huizhen Zhang
Microcystin-LR (MC-LR) is a ubiquitous peptide that exhibits strong reproductive toxicity, although the mechanistic basis for such toxicity remains largely unknown. The present study was conducted to investigate the mechanisms underlying the adverse effects of exposure to MC-LR in Chinese hamster ovary (CHO) cells. The results showed that MC-LR inhibited the in vitro proliferation of CHO cells significantly, with an IC50 of 10 μM. Moreover, MC-LR-treated CHO cells revealed strong induction of cell cycle arrest and apoptosis...
2016: Frontiers in Physiology
https://www.readbyqxmd.com/read/27875637/ambra1-a-novel-%C3%AE-synuclein-binding-protein-is-implicated-in-the-pathogenesis-of-multiple-system-atrophy
#18
Yasuo Miki, Kunikazu Tanji, Fumiaki Mori, Yota Tatara, Jun Utsumi, Hidenao Sasaki, Akiyoshi Kakita, Hitoshi Takahashi, Gian Maria Fimia, Koichi Wakabayashi
The accumulation of abnormal α-synuclein is the major histopathological feature of Lewy body disease and multiple system atrophy (MSA), which are referred to as synucleinopathies. Although the pathomechanisms underlying synucleinopathies are still unknown, mounting evidence indicates that cytoplasmic degradation systems, such as the autophagy-lysosome and proteasome pathways, are strongly involved in their pathogenesis. Autophagy is tightly regulated by several upstream proteins including UNC-51-like kinase 1/2, beclin1, vacuolar protein sorting-associated protein 34, and autophagy/beclin1 regulator 1 (AMBRA1)...
November 22, 2016: Brain Pathology
https://www.readbyqxmd.com/read/27875278/ratiometric-analysis-of-acridine-orange-staining-in-the-study-of-acidic-organelles-and-autophagy
#19
Marcos P Thomé, Eduardo C Filippi-Chiela, Emilly S Villodre, Celina B Migliavaca, Giovana R Onzi, Karina B Felipe, Guido Lenz
Acridine Orange is a cell-permeable green fluorophore that can be protonated and trapped in acidic vesicular organelles (AVOs). Its metachromatic shift to red fluorescence is concentration-dependent and, therefore, Acridine Orange fluoresces red in AVOs, such as autolysosomes. This makes Acridine Orange staining a quick, accessible and reliable method to assess the volume of AVOs, which increases upon autophagy induction. Here, we describe a ratiometric analysis of autophagy using Acridine Orange, considering the red-to-green fluorescence intensity ratio (R/GFIR) to quantify flow cytometry and fluorescence microscopy data of Acridine-Orange-stained cells...
December 15, 2016: Journal of Cell Science
https://www.readbyqxmd.com/read/27872163/role-of-autophagy-in-cadmium-induced-testicular-injury
#20
Y-J Wang, J Yan, F Yin, L Li, Y-G Qin, C-Y Meng, R-F Lu, L Guo
The testis is sensitive to cadmium, but studies investigating cadmium-induced testicular injury have not yet clearly revealed the underlying mechanisms. This study aimed to investigate the injurious effects of cadmium on rat testes and the role that autophagy plays in this process. Wistar rats were randomly divided into four groups and intraperitoneally injected with 0.2 (low), 0.4 (middle), and 0.8 mg/kg·body weight (high) cadmium chloride for 5 weeks, while the control rats were injected with equal volume of saline...
November 21, 2016: Human & Experimental Toxicology
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