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Autophage and 继发性甲状旁腺功能亢进

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https://www.readbyqxmd.com/read/28749469/zinc-oxide-nanoparticles-harness-autophagy-to-induce-cell-death-in-lung-epithelial-cells
#1
Jun Zhang, Xia Qin, Bin Wang, Ge Xu, Zhexue Qin, Jian Wang, Lanxiang Wu, Xiangwu Ju, Diptiman D Bose, Feng Qiu, Honghao Zhou, Zhen Zou
Although zinc oxide nanoparticles (ZnONPs) are widely used, they have raised concerns of toxicity in humans. Previous studies have indicated that reactive oxygen species (ROS) and autophagy are involved in the cytotoxicity of ZnONPs, but the regulatory mechanisms between autophagy and ROS remain to be elucidated. Herein, we comprehensively investigated the regulatory mechanism of autophagy and the link between autophagy and ROS in ZnONPs-treated lung epithelial cells. We demonstrated that ZnONPs could induce autophagy, and this process could enhance the dissolution of ZnONPs in lysosomes to release zinc ions...
July 27, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28748573/a-novel-humanized-anti-tumor-necrosis-factor-related-apoptosis-inducing-ligand-r2-monoclonal-antibody-induces-apoptotic-and-autophagic-cell-death
#2
Longfei Chen, Yuhe Qiu, Zhenliang Hao, Jiong Cai, Shuyong Zhang, Yanxin Liu, Dexian Zheng
It is well known that the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL/TNFSF10) is specifically expressed in various tumor cells, but less or no expression in most normal tissues and cells. While TRAIL engages with its native death receptors, TRAIL receptor 1 (TRAIL-R1) or 2 (TRAIL-R2), usually elicits the tumor cell death by apoptosis. In this study, we report that a novel humanized monoclonal antibody against TRAIL-R2 (named as zaptuzumab) well remain the biological activity of the parental mouse antibody AD5-10 inducing cell death in various cancer cells, but little effect on normal cells...
July 27, 2017: IUBMB Life
https://www.readbyqxmd.com/read/28743815/galectin-3-inhibits-galectin-8-parkin-mediated-ubiquitination-of-group-a-streptococcus
#3
Yi-Lin Cheng, Yan-Wei Wu, Chih-Feng Kuo, Shiou-Ling Lu, Fu-Tong Liu, Robert Anderson, Chiou-Feng Lin, Yi-Ling Liu, Wan-Yu Wang, Ying-Da Chen, Po-Xing Zheng, Jiunn-Jong Wu, Yee-Shin Lin
Group A streptococcus (GAS) is an important human pathogen that causes a wide variety of cutaneous and systemic infections. Although originally thought to be an extracellular bacterium, numerous studies have demonstrated that GAS can trigger internalization into nonimmune cells to escape from immune surveillance or antibiotic-mediated killing. Epithelial cells possess a defense mechanism involving autophagy-mediated targeting and killing of GAS within lysosome-fused autophagosomes. In endothelial cells, in contrast, we previously showed that autophagy is not sufficient for GAS killing...
July 25, 2017: MBio
https://www.readbyqxmd.com/read/28743755/ubiquitination-of-exposed-glycoproteins-by-scf-fbxo27-directs-damaged-lysosomes-for-autophagy
#4
Yukiko Yoshida, Sayaka Yasuda, Toshiharu Fujita, Maho Hamasaki, Arisa Murakami, Junko Kawawaki, Kazuhiro Iwai, Yasushi Saeki, Tamotsu Yoshimori, Noriyuki Matsuda, Keiji Tanaka
Ubiquitination functions as a signal to recruit autophagic machinery to damaged organelles and induce their clearance. Here, we report the characterization of FBXO27, a glycoprotein-specific F-box protein that is part of the SCF (SKP1/CUL1/F-box protein) ubiquitin ligase complex, and demonstrate that SCF(FBXO27) ubiquitinates glycoproteins in damaged lysosomes to regulate autophagic machinery recruitment. Unlike F-box proteins in other SCF complexes, FBXO27 is subject to N-myristoylation, which localizes it to membranes, allowing it to accumulate rapidly around damaged lysosomes...
July 25, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28741645/inflammasome-and-autophagy-regulation-a-two-way-street
#5
Qian Sun, Jie Fan, Timothy R Billiar, Melanie J Scott
Inflammation plays a significant role in protecting hosts against pathogens. Inflammation induced by non-infectious, endogenous agents can be detrimental, and if excessive can result in organ and tissue damage. The inflammasome is a major innate immune pathway that can be activated via both exogenous pathogen-associated molecular patterns (PAMPs) and endogenous damage-associated molecular patterns (DAMPs). Inflammasome activation involves formation and oligomerization of a protein complex including a NOD-like receptor (NLR), an adaptor protein (ASC) and procaspase-1...
July 24, 2017: Molecular Medicine
https://www.readbyqxmd.com/read/28741157/eicosapentaenoic-acid-protects-cardiomyoblasts-from-lipotoxicity-in-an-autophagy-dependent-manner
#6
Hsiu-Ching Hsu, Sin-Jin Li, Ching-Yi Chen, Ming-Fong Chen
BACKGROUND AND AIMS: The cardiovascular health benefits of eicosapentaenoic acid (EPA) have been demonstrated previously; however, the exact mechanism underlying them remains unclear. Our previous study found that lipotoxicity induced cardiomyocyte apoptosis via the inhibition of autophagy. Accordingly, in this study, we investigated whether EPA attenuated lipotoxicity-induced cardiomyocyte apoptosis through autophagy regulation. The role of EPA in mitochondrial dynamics was analyzed as well...
July 24, 2017: Cell Biology and Toxicology
https://www.readbyqxmd.com/read/28740552/npm1-mutant-mediated-pml-delocalization-and-stabilization-enhances-autophagy-and-cell-survival-in-leukemic-cells
#7
Qin Zou, Shi Tan, Zailin Yang, Qian Zhan, Hongjun Jin, Jingrong Xian, Shuaishuai Zhang, Liyuan Yang, Lu Wang, Ling Zhang
Accumulating evidence has defined nucleophosmin 1 (NPM1) mutation as a driver genetic event in acute myeloid leukemia (AML), whereas the pathogenesis of NPM1-mutated AML remains to be fully elucidated. In this study, we showed that mutant NPM1 elevated autophagic activity and autophagic activation contributed to leukemic cell survival in vitro. Meanwhile, we also found high expression of promyelocytic leukemia gene (PML) and its cytoplasmic dislocation in primary NPM1-mutated AML blasts and NPM1-mA positive OCI-AML3 cells...
2017: Theranostics
https://www.readbyqxmd.com/read/28740220/the-tnfaip8-pe-complex-is-a-novel-upstream-effector-in-the-anti-autophagic-action-of-insulin
#8
Ji-Soo Kim, Jimin Park, Mi-Sun Kim, Ji-Young Ha, Ye-Won Jang, Dong Hae Shin, Jin H Son
Defective hepatic autophagy is observed in obesity and diabetes, whereas autophagy is inhibited by insulin in hepatocytes. Insulin-induced anti-autophagy is mediated by non-canonical Gαi3 signaling via an unknown mechanism. Previously, we identified the anti-autophagic activity of Tnfaip8 via activation of mammalian target of rapamycin (mTOR) in the nervous system. Here, we demonstrate that insulin temporally induces Tnfaip8, which mediates the anti-autophagic action of insulin through formation of a novel ternary complex including Tnfaip8, phosphatidylethanolamine (PE) and Gαi3...
July 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28737825/combination-of-rapamycin-and-garlic-derived-s-allylmercaptocysteine-induces-colon-cancer-cell-apoptosis-and-suppresses-tumor-growth-in-xenograft-nude-mice-through-autophagy-p62-nrf2-pathway
#9
Siying Li, Guang Yang, Xiaosong Zhu, Lin Cheng, Yueyue Sun, Zhongxi Zhao
The natural plant-derived product S-allylmercapto-cysteine (SAMC) has been studied in cancer therapy as a single and combination chemotherapeutic agent. The present study was employed to verify the combination use of SAMC and rapamycin that is the mTOR inhibitor with anticancer ability but has limited efficacy due to drug resistance, and to explore the underlying mechanisms. We combined rapamycin and SAMC for colorectal cancer treatment in the HCT‑116 cancer cells and a xenograft murine model. The in vivo study was established by xenografting HCT‑116 cells in BALB/c nude mice...
July 24, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28737703/autophagy-and-human-neurodegenerative-diseases-a-fly-s-perspective
#10
REVIEW
Myungjin Kim, Allison Ho, Jun Hee Lee
Neurodegenerative diseases in humans are frequently associated with prominent accumulation of toxic protein inclusions and defective organelles. Autophagy is a process of bulk lysosomal degradation that eliminates these harmful substances and maintains the subcellular environmental quality. In support of autophagy's importance in neuronal homeostasis, several genetic mutations that interfere with autophagic processes were found to be associated with familial neurodegenerative disorders. In addition, genetic mutations in autophagy-regulating genes provoked neurodegenerative phenotypes in animal models...
July 23, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28733250/sphingosine-kinase-1-protects-renal-tubular-epithelial-cells-from-renal-fibrosis-via-induction-of-autophagy
#11
Chunyang Du, Yunzhuo Ren, Fang Yao, Jialiang Duan, Hui'er Zhao, Yunxia Du, Xia Xiao, Huijun Duan, Yonghong Shi
Autophagy is an important homoeostatic mechanism for the lysosomal degradation of protein aggregates and damaged cytoplasmic components. Recent studies suggest that autophagy which is induced by TGF-β1 suppresses kidney fibrosis in renal tubular epithelial cells (RTECs) of obstructed kidneys. Sphingosine kinase 1(SK1), converting sphingosine into endogenous sphingosine-1-phosphate (S1P), was shown to modulate autophagy and involved in the processes of fibrotic diseases. Since SK1 activity is also up-regulated by TGF-β1, we explored its effect on the induction of autophagy and development of renal fibrosis in this study...
July 18, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/28733114/targeting-heat-shock-factor-1-as-an-antiviral-strategy-against-dengue-virus-replication-in%C3%A2-vitro-and-in%C3%A2-vivo
#12
Tsung-Ting Tsai, Chia-Ling Chen, Cheng-Chieh Tsai, Chiou-Feng Lin
Fever onset is correlated with viremia in dengue virus (DENV) patients. Heat shock factor 1 (HSF1), a heat stress response host transcription factor, plays a crucial role in regulating multiple cellular functions, as well as the onset of infectious diseases. This study evaluated the role of HSF1 in DENV replication as a means of regulating DENV infection in vitro and in vivo. DENV infection activated HSF1 in both Ca(2+) and protein kinase A-dependent manners. Inhibiting HSF1 effectively reduced DENV replication, not only in THP-1 cells but also in primary human monocytes...
July 18, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28730238/altered-expression-of-mtor-and-autophagy-in-term-normal-human-placentas
#13
Qiu Xia Zhang, Quan Na, Weiwei Song
Mammalian target of rapamycin (mTOR) and autophagy have been implied in trophoblast cells proliferation and invasion. This study investigated whether mTOR and autophagy were involved in placental development and fetal programming. A total of 90 term normal placentas (37-42 gestational weeks) were collected from women who underwent elective cesarean section, with large for gestational age (LGA), fetal growth restriction (FGR), and appropriate for gestational age (AGA) infants (n=30, respectively). Capillary volume density within peripheral villi significantly decreased in the FGR placentas compared with the AGA group (p<0...
2017: Romanian Journal of Morphology and Embryology, Revue Roumaine de Morphologie et Embryologie
https://www.readbyqxmd.com/read/28729825/dexmedetomidine-protects-mouse-brain-from-ischemia-reperfusion-injury-via-inhibiting-neuronal-autophagy-through-up-regulating-hif-1%C3%AE
#14
Cong Luo, Ming-Wen Ouyang, Ying-Ying Fang, Shu-Ji Li, Quan Zhou, Jun Fan, Zai-Sheng Qin, Tao Tao
Stroke is the leading cause of death in China and produces a heavy socio-economic burden in the past decades. Previous studies have shown that dexmedetomidine (DEX) is neuroprotective after cerebral ischemia. However, the role of autophagy during DEX-mediated neuroprotection after cerebral ischemia is still unknown. In this study, we found that post-conditioning with DEX and DEX+3-methyladenine (3-MA) (autophagy inhibitor) reduced brain infarct size and improved neurological deficits compared with DEX+RAPA (autophagy inducer) 24 h after transient middle cerebral artery artery occlusion (tMCAO) model in mice...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28729463/dietary-pufas-attenuate-nlrp3-inflammasome-activation-via-enhancing-macrophage-autophagy
#15
Lulu Shen, Yan Yang, Tiantong Ou, Chia-Chi C Key, Sarah H Tong, Russel C Sequeira, Jonathan M Nelson, Yan Nie, Zhan Wang, Elena Boudyguina, Swapnil V Shewale, Xuewei Zhu
Dietary PUFAs reduce atherosclerosis and macrophage inflammation, but how NLRP3 inflammasome activation and autophagy influence PUFA-mediated atheroprotection is poorly understood. We fed Ldlr-/- mice diets containing 10% (calories) palm oil (PO) and 0.2% cholesterol, supplemented with an additional 10% of calories as PO, fish oil (FO), echium oil (EO, containing 18:4 n-3), or borage oil (BO, containing 18:3 n-6). Inflammasome activation, autophagic flux, and mitochondrial function were measured in peritoneal macrophages, blood monocytes, or liver from diet-fed mice...
July 20, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28729213/physical-exercise-increases-sestrin-2-protein-levels-and-induces-autophagy-in-the-skeletal-muscle-of-old-mice
#16
Luciene Lenhare, Barbara M Crisol, Vagner R R Silva, Carlos K Katashima, André V Cordeiro, Karina D Pereira, Augusto D Luchessi, Adelino S R da Silva, Dennys E Cintra, Leandro P Moura, José R Pauli, Eduardo R Ropelle
Sestrins and autophagy deficiencies are associated with several aging-related organic dysfunctions and metabolic disorders. Here we evaluate the effects of acute exercise on Sestrin 2 (Sesn2) protein content and autophagy markers in the skeletal muscle of experimental models of aging. Twenty-four months-old C57BL/6J male mice were submitted to a single bout of swimming exercise and the gastrocnemius muscle was evaluated by Western blot. Transcriptomic and phenotypic analysis were also performed by using strains of genetically-diverse BXD mice...
July 17, 2017: Experimental Gerontology
https://www.readbyqxmd.com/read/28728544/cladosporol-a-triggers-apoptosis-sensitivity-by-ros-mediated-autophagic-flux-in-human-breast-cancer-cells
#17
Mytre Koul, Ashok Kumar, Ramesh Deshidi, Vishal Sharma, Rachna D Singh, Jasvinder Singh, Parduman Raj Sharma, Bhawal Ali Shah, Sundeep Jaglan, Shashank Singh
BACKGROUND: Endophytes have proven to be an invaluable resource of chemically diverse secondary metabolites that act as excellent lead compounds for anticancer drug discovery. Here we report the promising cytotoxic effects of Cladosporol A (HPLC purified >98%) isolated from endophytic fungus Cladosporium cladosporioides collected from Datura innoxia. Cladosporol A was subjected to in vitro cytotoxicity assay against NCI60 panel of human cancer cells using MTT assay. We further investigated the molecular mechanism(s) of Cladosporol A induced cell death in human breast (MCF-7) cancer cells...
July 20, 2017: BMC Cell Biology
https://www.readbyqxmd.com/read/28726781/autophagy-inhibition-reduces-chemoresistance-and-tumorigenic-potential-of-human-ovarian-cancer-stem-cells
#18
Anna Pagotto, Giorgia Pilotto, Elena Laura Mazzoldi, Maria Ornella Nicoletto, Simona Frezzini, Anna Pastò, Alberto Amadori
Epithelial ovarian cancer (EOC) is one of the most malignant gynecological tumors with a high mortality rate owing to tumor relapse after anticancer therapies. It is widely accepted that a rare tumor cell population, known as cancer stem cells (CSC), is responsible for tumor progression and relapse; intriguingly, these cells are able to survive nutrient starvation (such as in vitro culture in the absence of glucose) and chemotherapy treatment. Recent data also indicated that chemotherapy resistance is associated with autophagy activation...
July 20, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28726776/autophagosome-maturation-mediated-by-rab7-contributes-to-neuroprotection-of-hypoxic-preconditioning-against-global-cerebral-ischemia-in-rats
#19
Lixuan Zhan, Siyuan Chen, Kongping Li, Donghai Liang, Xinyong Zhu, Liu Liu, Zhiwei Lu, Weiwen Sun, En Xu
Autophagy disruption leads to neuronal damage in hypoxic-ischemic brain injury. Rab7, a member of the Rab GTPase superfamily, has a unique role in the regulation of autophagy. Hypoxic preconditioning (HPC) provides neuroprotection against transient global cerebral ischemia (tGCI). However, the underlying mechanisms remain poorly understood. Thus, the current study explored the potential molecular mechanism of the neuroprotective effect of HPC by investigating how Rab7 mediates autophagosome (AP) maturation after tGCI in adult rats...
July 20, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28725634/ip3-receptor-mediated-calcium-signaling-and-its-role-in-autophagy-in-cancer
#20
REVIEW
Elzbieta Kania, Gemma Roest, Tim Vervliet, Jan B Parys, Geert Bultynck
Calcium ions (Ca(2+)) play a complex role in orchestrating diverse cellular processes, including cell death and survival. To trigger signaling cascades, intracellular Ca(2+) is shuffled between the cytoplasm and the major Ca(2+) stores, the endoplasmic reticulum (ER), the mitochondria, and the lysosomes. A key role in the control of Ca(2+) signals is attributed to the inositol 1,4,5-trisphosphate (IP3) receptors (IP3Rs), the main Ca(2+)-release channels in the ER. IP3Rs can transfer Ca(2+) to the mitochondria, thereby not only stimulating core metabolic pathways but also increasing apoptosis sensitivity and inhibiting basal autophagy...
2017: Frontiers in Oncology
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