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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/29346563/lc3-immunostaining-in-the-inferior-olivary-nuclei-of-cats-with-niemann-pick-disease-type-c1-is-associated-with-patterned-purkinje-cell-loss
#1
Brittney L Gurda, Jessica H Bagel, Samantha J Fisher, Mark L Schultz, Andrew P Lieberman, Peter Hand, Charles H Vite, Gary P Swain
The feline model of Niemann-Pick disease, type C1 (NPC1) recapitulates the clinical, neuropathological, and biochemical abnormalities present in children with NPC1. The hallmarks of disease are the lysosomal storage of unesterified cholesterol and multiple sphingolipids in neurons, and the spatial and temporal distribution of Purkinje cell death. In feline NPC1 brain, microtubule-associated protein 1 light chain 3 (LC3) accumulations, indicating autophagosomes, were found within axons and presynaptic terminals...
January 13, 2018: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/29346421/the-absence-of-specific-yeast-heat-shock-proteins-leads-to-abnormal-aggregation-and-compromised-autophagic-clearance-of-mutant-huntingtin-proteins
#2
Ryan Higgins, Marie-Helene Kabbaj, Alexa Hatcher, Yanchang Wang
The functionality of a protein depends on its correct folding, but newly synthesized proteins are susceptible to aberrant folding and aggregation. Heat shock proteins (HSPs) function as molecular chaperones that aid in protein folding and the degradation of misfolded proteins. Trinucleotide (CAG) repeat expansion in the Huntingtin gene (HTT) results in the expression of misfolded Huntingtin protein (Htt), which contributes to the development of Huntington's disease. We previously found that the degradation of mutated Htt with polyQ expansion (Htt103QP) depends on both ubiquitin proteasome system and autophagy...
2018: PloS One
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/29344913/cardiac-basal-autophagic-activity-and-increased-exercise-capacity
#4
Fang-Hui Li, Tao Li, Ying-Min Su, Jing-Yi Ai, Rui Duan, Timon Cheng-Yi Liu
To investigate whether high-intensity interval training (HIIT) and continuous moderate-intensity training (CMT) have different impacts on exercise performance and cardiac function and to determine the influence of these exercise protocols on modulating basal autophagy in the cardiac muscle of rats. Rats were assigned to three groups: sedentary control (SC), CMT, and HIIT. Total exercise volume and mean intensity were matched between the two protocols. After a 10-week training program, rats were evaluated for exercise performance, including exercise tolerance and grip strength...
January 17, 2018: Journal of Physiological Sciences: JPS
https://www.readbyqxmd.com/read/29344310/drug-repurposing-screening-identifies-tioconazole-as-an-atg4-inhibitor-that-suppresses-autophagy-and-sensitizes-cancer-cells-to-chemotherapy
#5
Pei-Feng Liu, Kun-Lin Tsai, Chien-Jen Hsu, Wei-Lun Tsai, Jin-Shiung Cheng, Hsueh-Wei Chang, Chung-Wai Shiau, Yih-Gang Goan, Ho-Hsing Tseng, Chih-Hsuan Wu, John C Reed, Lee-Wei Yang, Chih-Wen Shu
Background: Tumor cells require proficient autophagy to meet high metabolic demands and resist chemotherapy, which suggests that reducing autophagic flux might be an attractive route for cancer therapy. However, this theory in clinical cancer research remains controversial due to the limited number of drugs that specifically inhibit autophagy-related (ATG) proteins. Methods: We screened FDA-approved drugs using a novel platform that integrates computational docking and simulations as well as biochemical and cellular reporter assays to identify potential drugs that inhibit autophagy-required cysteine proteases of the ATG4 family...
2018: Theranostics
https://www.readbyqxmd.com/read/29344294/cardiomyocyte-restricted-low-density-lipoprotein-receptor-related-protein-6-lrp6-deletion-leads-to-lethal-dilated-cardiomyopathy-partly-through-drp1-signaling
#6
Zhidan Chen, Yang Li, Ying Wang, Juying Qian, Hong Ma, Xiang Wang, Guoliang Jiang, Ming Liu, Yanpeng An, Leilei Ma, Le Kang, Jianguo Jia, Chunjie Yang, Guoping Zhang, Ying Chen, Wei Gao, Mingqiang Fu, Zheyong Huang, Huiru Tang, Yichun Zhu, Junbo Ge, Hui Gong, Yunzeng Zou
Low density lipoprotein receptor-related protein 6 (LRP6), a wnt co-receptor, regulates multiple functions in various organs. However, the roles of LRP6 in the adult heart are not well understood. Methods: We observed LRP6 expression in heart with end-stage dilated cardiomyopathy (DCM) by western blot. Tamoxifen-inducible cardiac-specific LRP6 knockout mouse was constructed. Hemodynamic and echocardiographic analyses were performed to these mice. Results: Cardiac LRP6 expression was dramatically decreased in patients with end-stage dilated cardiomyopathy (DCM) compared to control group...
2018: Theranostics
https://www.readbyqxmd.com/read/29342507/the-role-of-autophagy-in-the-degradation-of-misfolded-hla-b27-heavy-chains
#7
Fatemeh Navid, Gerlinde Layh-Schmitt, Keith A Sikora, Antony Cougnoux, Robert A Colbert
OBJECTIVE: To determine whether autophagy is involved in the degradation of misfolded HLA-B27 in experimental spondyloarthritis. METHODS: Bone marrow derived macrophages from HLA-B27 and human β2 m (hβ2 m) transgenic rats were examined with and without IFNγ and proteasome or autophagy inhibitors. Immunoprecipitation, western blotting, and immunofluorescence were used to measure HLA-B27 heavy chains and autophagy. Autophagy was induced using rapamycin. HLA-B7/hβ2 m transgenic and wild type rat macrophages were used as controls...
January 17, 2018: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/29341130/mitochondrial-function-and-autophagy-integrating-proteotoxic-redox-and-metabolic-stress-in-parkinson-s-disease
#8
REVIEW
Jianhua Zhang, M Lillian Culp, Jason G Craver, Victor Darley-Usmar
Parkinson's disease (PD) is a movement disorder with widespread neurodegeneration in the brain. Significant oxidative, reductive, metabolic, and proteotoxic alterations have been observed in PD postmortem brains. The alterations of mitochondrial function resulting in decreased bioenergetic health is important and needs to be further examined to help develop biomarkers for PD severity and prognosis. It is now becoming clear that multiple hits on metabolic and signaling pathways are likely to exacerbate PD pathogenesis...
January 17, 2018: Journal of Neurochemistry
https://www.readbyqxmd.com/read/29340076/mitochondrial-ros-activates-erk-autophagy-pathway-as-a-protected-mechanism-against-deoxypodophyllotoxin-induced-apoptosis
#9
Sang-Hun Kim, Kwang-Youn Kim, Sul-Gi Park, Sun-Nyoung Yu, Young-Wook Kim, Hyo-Won Nam, Hyun-Hee An, Young-Woo Kim, Soon-Cheol Ahn
Deoxypodophyllotoxin (DPT) is a naturally occurring flavolignan isolated from Anthriscus sylvestris. Recently, it has been reported that DPT inhibits tubulin polymerization and induces G2/M cell cycle arrest followed by apoptosis through multiple cellular processes. Despite these findings, details regarding the cellular and molecular mechanisms underlying the DPT-mediated cell death have been poorly understood. To define a mechanism of DPT-mediated cell death response, we examined whether DPT activates signaling pathways for autophagy and apoptosis...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29339400/intact-glucose-uptake-despite-deteriorating-signaling-in-adipocytes-with-high-fat-feeding
#10
Björn Hansson, Sebastian Wasserstrom, Björn Moren, Vipul Periwal, Petter Vikman, Sam Cushman, Olga Göransson, Petter Storm, Karin Stenkula
To capture immediate cellular changes during diet-induced expansion of adipocyte cell volume and number, we characterized mature adipocytes during a short-term high-fat diet (HFD) intervention. Male C57BL6/J mice were fed chow diet, and then switched to HFD for 2, 4, 6 or 14 days. Systemic glucose clearance was assessed by glucose tolerance test. Adipose tissue was dissected for RNA-seq and cell size distribution analysis using coulter counting. Insulin response in isolated adipocytes was monitored by glucose uptake assay and western blotting, and confocal microscopy was used to assess autophagic activity...
January 16, 2018: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/29339380/negative-regulation-of-the-keap1-nrf2-pathway-by-a-p62-sqstm1-splicing-variant
#11
Shun Kageyama, Tetsuya Saito, Miki Obata, Ryo-Hei Koide, Yoshinobu Ichimura, Masaaki Komatsu
A key anti-oxidant pathway, the Keap1-Nrf2 system, is regulated by p62/Sqstm1 via multiple mechanisms, including gene expression, post-translational modifications such as ubiquitination and phosphorylation, and autophagic degradation of p62/Sqstm1 and Keap1. Herein, we demonstrate a novel mode of regulation of the Keap1-Nrf2 system, mediated by a splicing variant of p62/Sqstm1 pre-mRNA. Ensembl database search and subsequent biochemical analyses in mice revealed the presence of an mRNA that encodes p62/Sqstm1 protein lacking the Keap1-interacting region (KIR), which is essential for the interaction with Keap1...
January 16, 2018: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/29339250/discovery-of-novel-hsp90-inhibitors-that-induced-apoptosis-and-impaired-autophagic-flux-in-a549-lung-cancer-cells
#12
Qun Wei, Jun-Ya Ning, Xi Dai, Yuan-Di Gao, Le Su, Bao-Xiang Zhao, Jun-Ying Miao
Heat shock protein 90 (HSP90) inhibition has aroused increasing enthusiasm in antitumor strategies in recent years. According to our previous studies, we synthesized a series of coumarin pyrazoline compounds HCP1-HCP6 that might be HSP90 inhibitors. Interactions between HCP1-HCP6 and HSP90 were examined and antitumor activities of them were investigated in A549 lung cancer cells. Results showed that all the six derivatives could interact with HSP90, in which HCP1 exhibited the best binding ability and inhibited the activity of HSP90...
January 10, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29337250/the-stim1-inhibitor-ml9-disrupts-basal-autophagy-in-cardiomyocytes-by-decreasing-lysosome-content
#13
S Shaikh, R Troncoso, D Mondaca-Ruff, V Parra, L Garcia, M Chiong, S Lavandero
Stromal-interaction molecule 1 (STIM1)-mediated store-operated Ca2+ entry (SOCE) plays a key role in mediating cardiomyocyte hypertrophy, both in vitro and in vivo. Moreover, there is growing support for the contribution of SOCE to the Ca2+ overload associated with ischemia/reperfusion injury. Therefore, STIM1 inhibition is proposed as a novel target for controlling both hypertrophy and ischemia/reperfusion-induced Ca2+ overload. Our aim was to evaluate the effect of ML9, a STIM1 inhibitor, on cardiomyocyte viability...
January 11, 2018: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/29337114/pathological-endogenous-%C3%AE-synuclein-accumulation-in-oligodendrocyte-precursor-cells-potentially-induces-inclusions-in-multiple-system-atrophy
#14
Seiji Kaji, Takakuni Maki, Hisanori Kinoshita, Norihito Uemura, Takashi Ayaki, Yasuhiro Kawamoto, Takahiro Furuta, Makoto Urushitani, Masato Hasegawa, Yusuke Kinoshita, Yuichi Ono, Xiaobo Mao, Tran H Quach, Kazuhiro Iwai, Valina L Dawson, Ted M Dawson, Ryosuke Takahashi
Glial cytoplasmic inclusions (GCIs), commonly observed as α-synuclein (α-syn)-positive aggregates within oligodendrocytes, are the pathological hallmark of multiple system atrophy. The origin of α-syn in GCIs is uncertain; there is little evidence of endogenous α-syn expression in oligodendrocyte lineage cells, oligodendrocyte precursor cells (OPCs), and mature oligodendrocytes (OLGs). Here, based on in vitro analysis using primary rat cell cultures, we elucidated that preformed fibrils (PFFs) generated from recombinant human α-syn trigger multimerization and an upsurge of endogenous α-syn in OPCs, which is attributable to insufficient autophagic proteolysis...
December 27, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/29337057/heterogeneity-of-autophagic-status-in-pancreatic-%C3%AE-cells-under-metabolic-stress
#15
Mai Kamitani, Takeshi Miyatsuka, Masaki Miura, Kosuke Azuma, Luka Suzuki, Miwa Himuro, Takehiro Katahira, Yuya Nishida, Yoshio Fujitani, Hirotaka Watada
Autophagy in β cells has been demonstrated to play a pivotal role in cellular homeostasis and the progression of glucose intolerance. Although autophagic activity is affected by metabolic stress both in vivo and in vitro, it remains unclear as to what extent the autophagic status in each β cell is different from its neighboring cells. To address this question, GFP-LC3 reporter mice, which can visualize the autophagic status of each β cell as green-fluorescent puncta, were crossed with obese diabetic db/db mice...
January 11, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29336468/increased-expression-of-sterol-regulatory-element-binding-protein%C3%A2-2-alleviates-autophagic-dysfunction-in-nafld
#16
Chunwei Cheng, Xiaoling Deng, Keshu Xu
Sterol regulatory element binding protein‑2 (SREBP‑2) is an important transcription factor in lipid homeostasis. A previous study showed that SREBP‑2 also activated autophagic genes during cell‑sterol depletion. Alterations in autophagy are reported to be involved in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). However, whether the regulation of SREBP‑2 restores dysfunctional autophagy in hepatocytes during NAFLD remains to be elucidated. In the present study, a steatosis model was established with palmitic acid (PA) treatment at the indicated times and concentrations...
January 16, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29336118/resveratrol-potently-counteracts-quercetin-starvation-induced-autophagy-and-sensitizes-hepg2-cancer-cells-to-apoptosis
#17
Sarah Tomas-Hernández, Jordi Blanco, Cristina Rojas, Joel Roca-Martínez, María José Ojeda-Montes, Raúl Beltrán-Debón, Santiago Garcia-Vallve, Gerard Pujadas, Lluís Arola, Miquel Mulero
SCOPE: Resveratrol (RSV) has been described as a potent antioxidant, anti-steatotic, and antitumor compound, and it has also been identified as a potent autophagy inducer. On the other hand, quercetin (QCT) is a dietary flavonoid with known antitumor, anti-inflammatory and antidiabetic effects. Additionally, QCT increases autophagy. To study the hypothetical synergistic effect of both compounds, we tested the combined effect of QCT and RSV on the autophagy process in HepG2 cells METHODS AND RESULTS: Autophagy was studied by western blotting, real-time RT-PCR, and cellular staining...
January 16, 2018: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/29333049/marine-derived-fungi-extracts-enhance-the-cytotoxic-activity-of-doxorubicin-in-nonsmall-cell-lung-cancer-cells-a459
#18
Bruno Castro-Carvalho, Alice A Ramos, Maria Prata-Sena, Fernanda Malhão, Márcia Moreira, Daniela Gargiulo, Tida Dethoup, Suradet Buttachon, Anake Kijjoa, Eduardo Rocha
Background: Drug resistance is a major concern in the current chemotherapeutic approaches and the combination with natural compounds may enhance the cytotoxic effects of the anticancer drugs. Therefore, this study evaluated the cytotoxicity of crude ethyl extracts of six marine-derived fungi - Neosartorya tsunodae KUFC 9213 (E1), Neosartorya laciniosa KUFC 7896 (E2), Neosartorya fischeri KUFC 6344 (E3), Aspergillus similanensis KUFA 0013 (E4), Neosartorya paulistensis KUFC 7894 (E5), and Talaromyces trachyspermum KUFC 0021 (E6) - when combined with doxorubicin (Dox), in seven human cancer cell lines...
December 2017: Pharmacognosy Research
https://www.readbyqxmd.com/read/29332356/%C3%AE-aescin-shows-potent-antiproliferative-activity-in-osteosarcoma-cells-by-inducing-autophagy-ros-generation-and-mitochondrial-membrane-potential-loss
#19
Zhao-Rui Liu, Li-Zhi Sun, Tang-Hong Jia, Dao-Fu Jia
PURPOSE: Osteosarcoma is one of the frequent bone tumor affecting mainly children and is associated with considerable mortality. The limited availability of anticancer drugs and less efficacious treatment options have led to poor survival rates of patients with osteosarcoma. Therefore, there is need to look for more viable treatment options and against this backdrop, natural products may prove handy. Therefore the aim of the present study was to evaluate the anticancer activity of a natural product of plant origin, β-aescin, against U2OS human osteosarcoma cells...
November 2017: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
https://www.readbyqxmd.com/read/29332352/puerarin-leads-to-k562-cell-apoptosis-of-chronic-myelogenous-leukemia-via-induction-of-autophagy
#20
Da Gao, Zhen Xiao, Hui-Ping Li
PURPOSE: To study the effects of puerarin on the viability, apoptosis and autophagy of K562 cells of chronic myelogenous leukemia (CML), and to provide a basis for the study on antitumor mechanism of puerarin. METHODS: K562 cells of human CML were taken as the study material and puerarin was applied in different concentrations. The effect of puerarin on cell viability was detected via cholecystokinin-8 (CCK8) and lactate dehydrogenase (LDH). Flow cytometry and western blot (WB) were used to detect cell apoptosis, while Cyto-ID and WB were used to detect the cell autophagy level...
November 2017: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
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