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https://www.readbyqxmd.com/read/28637004/autophagy-is-required-for-crizotinib-induced-apoptosis-in-met-amplified-gastric-cancer-cells
#1
Rebecca D Schroeder, Woonyoung Choi, David S Hong, David J McConkey
MET amplification has been clinically credentialed as a therapeutic target in gastric cancer, but the molecular mechanisms underlying sensitivity and resistance to MET inhibitors are still not well understood. Using whole-genome mRNA expression profiling, we identified autophagy as a top molecular pathway that was activated by the MET inhibitor crizotinib in drug-sensitive human gastric cancer cells, and functional studies confirmed that crizotinib increased autophagy levels in the drug-sensitive cells in a concentration-dependent manner...
June 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28630390/kavalactone-yangonin-induces-autophagy-and-sensitizes-bladder-cancer-cells-to-flavokawain-a-and-docetaxel-via-inhibition-of-the-mtor-pathway
#2
Liu Zhongbo, Ha U-Syn, Yu Ke, Wu Chunli, Yokoyama Noriko, Zi Xiaolin
Consumption of kava (Piper methysticum Forst) has been linked to reduced cancer risk in the South Pacific Islands. Kavalactones are major bioactive components in kava root extracts, which have recently demonstrated anti-cancer activities. However, molecular mechanisms of kavalactones' anti-cancer action remain largely unknown. We have identified two kavalactones, yangonin and 5' 6'-dehydrokawain, as potent inducers of autophagic cell death in bladder cancer cells. The effect of yangonin inducing autophagy is associated with increased expression of beclin and ATG5...
June 20, 2017: Journal of Biomedical Research
https://www.readbyqxmd.com/read/28625130/remote-ischemic-conditioning-improves-cognitive-function-during-cerebral-vascular-injury-through-the-induction-of-autophagy
#3
Hongjuan Wang, Yang Xu, Hetao Bian, Cuiping Si, Zhongrui Yan, Meijia Zhu
BACKGROUND: The most valid model for vascular cognitive impairment (VCI) is the mouse bilateral common carotid artery stenosis (BCAS), whose behavioral outcomes is supposedly affected by the remote ischemic conditioning (RIC) through the induction of autophgy. We hope to determine whether RIC contributes to the neuroprotection through the induction of autophagy.. METHODS: Wastar male mice were randomized into three groups including the Sham, the BCAS and the RIC+BCAS groups...
June 18, 2017: Current Neurovascular Research
https://www.readbyqxmd.com/read/28617531/controlled-release-mitomycin-c-polylactic-acid-film-prevents-epidural-scar-hyperplasia-after-laminectomy-by-inducing-fibroblast-autophagy-and-regulating-the-expression-of-mirnas
#4
B-B Wang, H Xie, T Wu, N Xie, J Wu, Y Gu, F Tang, J Liu
OBJECTIVE: To design a new controlled-release MMC-PLA film and explore whether and how this film could prevent epidural scar hyperplasia and adhesion in a post-laminectomy rat model. MATERIALS AND METHODS: All procedures were performed under the approval and supervision of the Institutional Animal Care and Use Committee (IACUC) of Nanjing Medical University. A total of 120 Sprague-Dawley (SD) rats were randomly placed into four groups after laminectomy (each group=30 rats)...
May 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28615727/oestrogen-inhibits-arterial-calcification-by-promoting-autophagy
#5
Yi-Qun Peng, Dan Xiong, Xiao Lin, Rong-Rong Cui, Feng Xu, Jia-Yu Zhong, Ting Zhu, Feng Wu, Min-Zhi Mao, Xiao-Bo Liao, Ling-Qing Yuan
Arterial calcification is a major complication of cardiovascular disease. Oestrogen replacement therapy in postmenopausal women is associated with lower levels of coronary artery calcification, but its mechanism of action remains unclear. Here, we show that oestrogen inhibits the osteoblastic differentiation of vascular smooth muscle cells (VSMCs) in vitro and arterial calcification in vivo by promoting autophagy. Through electron microscopy, GFP-LC3 redistribution, and immunofluorescence analyses as well as measurement of the expression of the autophagosome marker light-chain I/II (LC3I/II) and autophagy protein 5 (Atg5), we show that autophagy is increased in VSMCs by oestrogen in vitro and in vivo...
June 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28607460/recombinant-thrombomodulin-exerts-anti-autophagic-action-in-endothelial-cells-and-provides-anti-atherosclerosis-effect-in-apolipoprotein-e-deficient-mice
#6
Po-Sheng Chen, Kuan-Chieh Wang, Ting-Hsing Chao, Hsing-Chun Chung, Shi-Ya Tseng, Chawn-Yau Luo, Guey-Yueh Shi, Hua-Lin Wu, Yi-Heng Li
Stress-induced alteration in endothelial cells (ECs) integrity precedes the development of atherosclerosis. Previous studies showed that the soluble recombinant thrombomodulin (rTM) not only increases ECs proliferation but also exerts anti-apoptotic activity in ECs. However, the functional significance of soluble rTM on autophagy-related apoptosis in ECs is still undetermined. Implicating a cytoprotective role for rTM in persistent serum starvation (SS)-induced autophagy in cultured ECs, we found that treatment of rTM decreased the expression of SS-induced autophagy-related proteins, ATG5 and LC3, and the formation of autophagosomes through activation of AKT/mTOR pathway...
June 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28607148/autophagy-downstream-of-endosomal-toll-like-receptors-signaling-in-macrophages-is-a-key-mechanism-for-resistance-to-leishmania-major-infection
#7
Luis H Franco, Anna K A Fleuri, Nat Aacutelia C Pellison, Gustavo F S Quirino, Catarina V Horta, Renan V H de Carvalho, Sérgio C Oliveira, Dario S Zamboni
Leishmaniasis is caused by protozoan parasites of the genus Leishmania. In mammalians, these parasites survive and replicate in macrophages and parasite elimination by macrophages is critical for host resistance. Endosomal Toll-like receptors (TLRs) have been shown to be crucial for resistance to L. major in vivo. For example, mice in the resistant C57BL/6 genetic background that are triple-deficient for TLR3, -7 and -9 (Tlr3/7/9-/-) are highly susceptible to L. major infection. Tlr3/7/9-/- mice are as susceptible as mice deficient in MyD88 or UNC93B1, a chaperone required for appropriate localization of endosomal TLRs, but the mechanisms are unknown...
June 12, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28603711/autophagy-in-the-vertebrate-inner-ear
#8
REVIEW
Marta Magariños, Sara Pulido, María R Aburto, Rocío de Iriarte Rodríguez, Isabel Varela-Nieto
Autophagy is a conserved catabolic process that results in the lysosomal degradation of cell components. During development, autophagy is associated with tissue and organ remodeling, and under physiological conditions it is tightly regulated as it plays a housekeeping role in removing misfolded proteins and damaged organelles. The vertebrate inner ear is a complex sensory organ responsible for the perception of sound and for balance. Cell survival, death and proliferation, as well as cell fate specification and differentiation, are processes that are strictly coordinated during the development of the inner ear in order to generate the more than a dozen specialized cell types that constitute this structure...
2017: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/28597984/dual-inhibition-of-bdnf-trkb-and-autophagy-a-promising-therapeutic-approach-for-colorectal-cancer
#9
Clément Mazouffre, Sophie Geyl, Aurélie Perraud, Sabrina Blondy, Marie-Odile Jauberteau, Muriel Mathonnet, Mireille Verdier
Colorectal cancer (CRC) is the most common digestive cancer in the Western world. Despite effective therapies, resistance and/or recurrence frequently occur. The present study investigated the impact of two survival pathways-neurotrophic factors (TrkB/BDNF) and autophagy-on cell fate and tumour evolution. In vitro studies were performed on two CRC cell lines, SW480 (primary tumour) and SW620 (lymph node invasion), which were also used for subcutaneous xenografts on a nude mouse model. In addition, the presence of neurotrophic factors (NTs) and autophagy markers were assessed in tissue samples representative of different stages...
June 9, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28594407/egr-1-aspp1-inter-regulatory-loop-promotes-apoptosis-by-inhibiting-cyto-protective-autophagy
#10
Kunming Zhao, Miao Yu, Yifu Zhu, Dong Liu, Qiong Wu, Ying Hu
The decrease of ASPP1 (Apoptosis-Stimulating Protein of p53 1), a known p53 activator, has been linked to carcinogenesis and the cytotoxic resistance in various cancers, yet the underlying mechanisms of ASPP1 expression and its complex functions are not yet clear. Here, we report that ASPP1 forms an inter-regulatory loop with Early Growth Response 1 (EGR-1), and promotes apoptosis via inhibiting cyto-protective autophagy, independent of the well-documented p53-dependent mechanisms. We show that ASPP1 mRNA and protein were remarkably elevated by ectopic EGR-1 expression or endogenous EGR-1 activation, in cells with different tissue origins and p53 status...
June 8, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28594401/upconversion-nanoparticle-mediated-photodynamic-therapy-induces-autophagy-and-cholesterol-efflux-of-macrophage-derived-foam-cells-via-ros-generation
#11
Xiaobo B Han, Hongxia X Li, Yueqing Q Jiang, Hao Wang, Xuesong S Li, Jiayuan Y Kou, Yinghong H Zheng, Zhongni N Liu, Hong Li, Jing Li, Dou Dou, You Wang, Ye Tian, Liming M Yang
Macrophage-derived foam cells are a major component of atherosclerotic plaques and have an important role in the progression of atherosclerotic plaques, thus posing a great threat to human health. Photodynamic therapy (PDT) has emerged as a therapeutic strategy for atherosclerosis. Here, we investigated the effect of PDT mediated by upconversion fluorescent nanoparticles encapsulating chlorin e6 (UCNPs-Ce6) on the cholesterol efflux of THP-1 macrophage-derived foam cells and explored the possible mechanism of this effect...
June 8, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28593135/evaluation-of-cell-death-pathways-initiated-by-antitumor-drugs-melatonin-and-valproic-acid-in-bladder-cancer-cells
#12
Siwei Liu, Bilin Liang, Huiting Jia, Yuhan Jiao, Zhongqiu Pang, Yongye Huang
Effective drug combinations have the potential to strengthen therapeutic efficacy and combat drug resistance. Both melatonin and valproic acid (VPA) exhibit antitumor activities in various cancer cells. The aim of this study was to evaluate the cell death pathways initiated by anticancer combinatorial effects of melatonin and VPA in bladder cancer cells. The results demonstrated that the combination of melatonin and VPA leads to significant synergistic growth inhibition of UC3 bladder cancer cells. Gene expression studies revealed that cotreatment with melatonin and VPA triggered the up-regulation of certain genes related to apoptosis (TNFRSF10A and TNFRSF10B), autophagy (BECN, ATG3 and ATG5) and necrosis (MLKL, PARP-1 and RIPK1)...
June 2017: FEBS Open Bio
https://www.readbyqxmd.com/read/28578340/microrna-30b-regulates-high-phosphorus-level-induced-autophagy-in-vascular-smooth-muscle-cells-by-targeting-becn1
#13
Jian Wang, Yi-Ting Sun, Tian-Hua Xu, Wei Sun, Bin-Yao Tian, Zi-Tong Sheng, Li Sun, Lin-Lin Liu, Jian-Fei Ma, Li-Ning Wang, Li Yao
BACKGROUND/AIMS: Autophagy is an evolutionarily conserved mechanism that affects the survival and functions of vascular smooth muscle cells (VSMCs). We explored the role of microRNAs (miRNAs) in regulating autophagy in VSMCs exposed to high phosphorus (Pi) levels. METHODS: VSMCs were isolated from the thoracic aorta of rats and were cultured primarily. Real-time PCR was used to measure the mRNA expression of indicated genes. Western blotting was performed to detect the protein expression of autophagy-related markers...
June 5, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28577568/pirfenidone-inhibits-myofibroblast-differentiation-and-lung-fibrosis-development-during-insufficient-mitophagy
#14
Yusuke Kurita, Jun Araya, Shunsuke Minagawa, Hiromichi Hara, Akihiro Ichikawa, Nayuta Saito, Tsukasa Kadota, Kazuya Tsubouchi, Nahoko Sato, Masahiro Yoshida, Kenji Kobayashi, Saburo Ito, Yu Fujita, Hirofumi Utsumi, Haruhiko Yanagisawa, Mitsuo Hashimoto, Hiroshi Wakui, Yutaka Yoshii, Takeo Ishikawa, Takanori Numata, Yumi Kaneko, Hisatoshi Asano, Makoto Yamashita, Makoto Odaka, Toshiaki Morikawa, Katsutoshi Nakayama, Kazuyoshi Kuwano
BACKGROUND: Pirfenidone (PFD) is an anti-fibrotic agent used to treat idiopathic pulmonary fibrosis (IPF), but its precise mechanism of action remains elusive. Accumulation of profibrotic myofibroblasts is a crucial process for fibrotic remodeling in IPF. Recent findings show participation of autophagy/mitophagy, part of the lysosomal degradation machinery, in IPF pathogenesis. Mitophagy has been implicated in myofibroblast differentiation through regulating mitochondrial reactive oxygen species (ROS)-mediated platelet-derived growth factor receptor (PDGFR) activation...
June 2, 2017: Respiratory Research
https://www.readbyqxmd.com/read/28574506/role-of-atg5-dependent-cell-death-in-the-embryonic-development-of-bax-bak-double-knockout-mice
#15
Satoko Arakawa, Masatsune Tsujioka, Tatsushi Yoshida, Hajime Tajima-Sakurai, Yuya Nishida, Yosuke Matsuoka, Ikuyo Yoshino, Yoshihide Tsujimoto, Shigeomi Shimizu
Programmed cell death, which is required for the development and homeostasis of metazoans, includes mechanisms such as apoptosis, autophagic cell death, and necrotic (or type III) death. Members of the Bcl2 family regulate apoptosis, among which Bax and Bak act as a mitochondrial gateway. Although embryonic fibroblasts from Bax/Bak double-knockout (DKO) mice are resistant to apoptosis, we previously demonstrated that these cells die through an autophagy-dependent mechanism in response to various types of cellular stressors...
June 2, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28573684/lc3-association-with-the-parasitophorous-vacuole-membrane-of-plasmodium-berghei-liver-stages-follows-a-non-canonical-autophagy-pathway
#16
Rahel Wacker, Nina Eickel, Jacqueline Schmuckli-Maurer, Takeshi Annoura, Livia Niklaus, Shahid M Khan, Jun-Lin Guan, Volker T Heussler
Eukaryotic cells can employ autophagy to defend themselves against invading pathogens. Upon infection by Plasmodium berghei sporozoites, the host hepatocyte targets the invader by labelling the parasitophorous vacuole membrane (PVM) with the autophagy marker protein LC3. Until now it has not been clear whether LC3 recruitment to the PVM is mediated by fusion of autophagosomes or by direct incorporation. To distinguish between these possibilities, we knocked out genes that are essential for autophagosome formation and for direct LC3 incorporation into membranes...
June 1, 2017: Cellular Microbiology
https://www.readbyqxmd.com/read/28569199/shikonin-induced-necroptosis-is-enhanced-by-the-inhibition-of-autophagy-in-non-small-cell-lung-cancer-cells
#17
Hyo-Jin Kim, Ki-Eun Hwang, Do-Sim Park, Seon-Hee Oh, Hong Young Jun, Kwon-Ha Yoon, Eun-Taik Jeong, Hak-Ryul Kim, Young-Suk Kim
BACKGROUND: Shikonin, a natural naphthoquinone pigment purified from Lithospermum erythrorhizon, induces necroptosis in various cancer types, but the mechanisms underlying the anticancer activity of shikonin in lung cancer are not fully understood. This study was designed to clarify whether shikonin causes necroptosis in non-small cell lung cancer (NSCLC) cells and to investigate the mechanism of action. METHODS: Multiplex and caspase 8 assays were used to analyze effect of shikonin on A549 cells...
May 31, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28562483/investigation-of-the-expression-of-apoptosis-inducing-factor-mediated-apoptosis-in-hirschsprung-s-disease
#18
Xin Ge, Chunyan Hu, Qingqing Guo, Wei Li, Yuying Zhao, Weili Yang, Yudu Wang, Peng Li, Ya Gao, Qiang Huang
One of the widely accepted hypotheses of Hirschsprung's disease (HD) is that the absence of ganglion cells in the distal part of the intestine is caused by the death of enteric neural crest-derived cells following migration. Although a caspase-dependent pathway has not yet been detected in the HD bowel, it is unclear whether a caspase-independent pathway contributes toward aganglionosis. In the current study, we observed highly condensed marginal heterochromatin in nuclei only in the transitional segment using electron microscopy and a high proportion of TUNEL-positive cells were observed in the transitional segment...
July 5, 2017: Neuroreport
https://www.readbyqxmd.com/read/28560460/synthetic-lethal-interaction-of-cdk-inhibition-and-autophagy-inhibition-in-human-solid-cancer-cell-lines
#19
Yoshinari Okada, Shunsuke Kato, Yasuhiro Sakamoto, Takayuki Oishi, Chikashi Ishioka
Cell cycle control is a promising target in cancer treatments, and some small-molecule cyclin-dependent kinase (CDK) inhibitors have exhibited clinical effectiveness. However, no biomarkers predictive of efficacy have been developed. Recent studies have revealed that CDK inhibitor (CKI) proteins, such as p27 and p16, also induced cytoprotective autophagy in cancer cells. However, it is unclear whether small-molecule CKIs also induce autophagy in solid tumors, as induced autophagy promotes cancer cell survival...
May 30, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28559895/autophagy-plays-an-important-role-in-anti-inflammatory-mechanisms-stimulated-by-alpha7-nicotinic-acetylcholine-receptor
#20
Bo-Zong Shao, Ping Ke, Zhe-Qi Xu, Wei Wei, Ming-He Cheng, Bin-Ze Han, Xiong-Wen Chen, Ding-Feng Su, Chong Liu
Alpha7 nicotinic acetylcholine receptor (α7nAChR) has been reported to alleviate neuroinflammation. Here, we aimed to determine the role of autophagy in α7nAChR-mediated inhibition of neuroinflammation and its underlying mechanism. Experimental autoimmune encephalomyelitis (EAE) mice and lipopolysaccharide-stimulated BV2 microglia were used as in vivo and in vitro models of neuroinflammation, respectively. The severity of EAE was evaluated with neurological scoring. Autophagy-related proteins (Beclin 1, LC3-II/I, p62/SQSTM1) were detected by immunoblot...
2017: Frontiers in Immunology
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