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https://www.readbyqxmd.com/read/29453806/cq-sensitizes-human-pancreatic-cancer-cells-to-gemcitabine-through-the-lysosomal-apoptotic-pathway-via-reactive-oxygen-species
#1
Zhiping Fu, Cheng Xi, Jie Kuang, Haoran Feng, Lingxie Chen, Juyong Liang, Xiaonan Shen, Stanley Yuen, Peng Chenghong, Shen Baiyong, Jin Zhijian, Weihua Qiu
As an established anti-cancer drug, gemcitabine (GEM) is an effective systemic treatment for advanced pancreatic cancer (PC). However, little is known about the potential effectors that may modify tumour cell sensitivity towards GEM. Autophagy, as a physiological cellular mechanism, is involved in both cell survival and cell death. In this study, we found that exposure to GEM induced a significant increase in autophagy in a dose-dependent manner in PANC-1 and BxPC-3 cells. Inhibition of autophagy by chloroquine (CQ) and ATG7 siRNA increased GEM-induced cytotoxicity, and CQ was more effective than ATG7 siRNA...
February 17, 2018: Molecular Oncology
https://www.readbyqxmd.com/read/29453569/assessing-autophagy-in-sertoli-cells
#2
Chao Liu, Jehangir Khan, Wei Li
Autophagy is an important cellular homeostatic process, it degrades most long-lived proteins and some organelles by lysosome to provide raw materials for the survival of the cells during nutrient or energy deprivation condition. Autophagy is active in Sertoli cells and involved in many cellular processes. However, the precise role of autophagy in Sertoli cells is still largely unknown. Thus, the assessment of autophagy in Sertoli cells should be helpful for investigating the functional roles of autophagy in Sertoli cells...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29453533/the-role-of-autophagy-in-nanoparticles-induced-toxicity-and-its-related-cellular-and-molecular-mechanisms
#3
Yubin Li, Dianwen Ju
In the past decades, nanoparticles have been widely used in industry and pharmaceutical fields for drug delivery, anti-pathogen, and diagnostic imaging purposes because of their unique physicochemical characteristics such as special ultrastructure, dispersity, and effective cellular uptake properties. But the nanotoxicity has been raised over the extensive applications of nanoparticles. Researchers have elucidated series of mechanisms in nanoparticles-induced toxicity, including apoptosis, necrosis, oxidative stress, and autophagy...
2018: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29453205/co-deficiency-of-lysosomal-mucolipins-3-and-1-in-cochlear-hair-cells-diminishes-outer-hair-cell-longevity-and-accelerates-age-related-hearing-loss
#4
Teerawat Wiwatpanit, Natalie N Remis, Aisha Ahmad, Yingjie Zhou, John C Clancy, Mary Ann Cheatham, Jaime García-Añoveros
Acquired hearing loss is the predominant neurodegenerative condition associated with aging in humans. Although mutations on several genes are known to cause congenital deafness in newborns, few genes have been implicated in age-related hearing loss (ARHL), perhaps because its cause is likely polygenic. Here, we generated mice lacking lysosomal calcium channel mucolipins 3 and 1 and discovered that both male and female mice suffered a polygenic form of hearing loss. While mucolipin 1 is ubiquitously expressed in all cells, mucolipin 3 is expressed in a small subset of cochlear cells -hair cells (HCs) and marginal cells of the stria vascularis- and very few other cell types...
February 16, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29452403/mechanisms-controlling-nucleic-acid-sensing-toll-like-receptors
#5
Kensuke Miyake, Takuma Shibata, Umeharu Ohto, Toshiyuki Shimizu, Shin-Ichiroh Saitoh, Ryutaro Fukui, Yusuke Murakami
Nucleic acid (NA)-sensing Toll-like receptors (TLRs) respond to DNA/RNA derived from pathogens and dead cells. Structural studies have revealed a variety of molecular mechanisms by which TLRs sense NAs. Double-stranded RNA and single-stranded DNA directly bind to TLR3 and TLR9, respectively, whereas TLR7 and 8 bind to nucleosides and oligoribonucleotides derived from RNAs. Activation of ligand-bound TLRs is influenced by the functional status of TLRs. Proteolytic cleavage of NA-sensing TLRs enables ligand-dependent TLR dimerization...
February 14, 2018: International Immunology
https://www.readbyqxmd.com/read/29452206/snx10-mediates-alcohol-induced-liver-injury-and-steatosis-via-regulating-chaperone-mediated-autophagy-activation
#6
Yan You, Wan-Zhen Li, Sulin Zhang, Bin Hu, Yue-Xuan Li, Hai-Dong Li, Huan-Huan Tang, Qian-Wen Li, Yun-Yun Guan, Li-Xin Liu, Wei-Lian Bao, Xiaoyan Shen
BACKGROUND & AIMS: Alcoholic liver disease is a major cause of morbidity and mortality worldwide. However, the cellular defense mechanisms underlying ALD are not well understood. Recent studies highlight the involvement of chaperone-mediated autophagy (CMA) in regulating hepatic lipid metabolism. Sorting nexin (SNX) 10 has a regulatory function in endo-lysosomal trafficking and stabilization. Here we investigated the roles of SNX10 in CMA activation and the pathogenesis of alcohol-induced liver injury and steatosis...
February 13, 2018: Journal of Hepatology
https://www.readbyqxmd.com/read/29452108/effect-of-brimonidine-an-%C3%AE-2-adrenergic-agonist-on-human-meibomian-gland-epithelial-cells
#7
Xi Han, Yang Liu, Wendy R Kam, David A Sullivan
We recently discovered that the anti-glaucoma pharmaceuticals timolol, a β adrenergic antagonist, and pilocarpine, a cholinergic compound, negatively influence the morphology, proliferative capacity and survival of human meibomian gland epithelial cells (HMGECs). We hypothesize that another class of anti-glaucoma drugs, the α2 adrenergic agonists, also acts directly on HMGECs to affect their structure and function. We tested this hypothesis. Immortalized (i) HMGECs were cultured with brimonidine, as well as clonidine (α2 agonist), phenylephrine (α1 agonist), RX821002 (inverse α2 agonist) and MK912 (neutral α2 agonist) for up to 7 days...
February 13, 2018: Experimental Eye Research
https://www.readbyqxmd.com/read/29451820/the-hcm-linked-w792r-mutation-in-cardiac-myosin-binding-protein-c-reduces-c6-fniii-domain-stability
#8
Dan F Smelter, Willem J De Lange, Wenxuan Cai, Ying Ge, John C Ralphe
Cardiac myosin binding protein-C (cMyBP-C) is a functional sarcomeric protein that regulates contractility in response to contractile demand, and many mutations in cMyBP-C lead to hypertrophic cardiomyopathy (HCM). To gain insight into the effects of disease-causing cMyBP-C missense mutations on contractile function, we expressed the pathogenic W792R mutation in mouse cardiomyocytes lacking endogenous cMyBP-C and studied the functional effects using three-dimensional engineered cardiac tissue (mECT) constructs...
February 16, 2018: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/29451150/identification-of-seven-novel-mutations-in-the-acid-alpha-glucosidase-gene-in-five-chinese-patients-with-late-onset-pompe-disease
#9
Hua-Xu Liu, Chuan-Qiang Pu, Qiang Shi, Yu-Tong Zhang, Rui Ban
Background: Pompe disease is a rare lysosomal glycogen storage disorder linked to the acid alpha-glucosidase gene (GAA). A wide clinical and genetic variability exists between patients from different ethnic populations, and the genotype-phenotype correlations are still not well understood. The aim of this study was to report the clinicopathological and genetic characteristics of five Chinese patients with late-onset Pompe disease (LOPD) who carried novel GAA gene mutations. Methods: Clinical and pathological data of patients diagnosed with glycogen storage disease at our institution from April 1986 to August 2017 were collected, and next-generation sequencing of frozen muscle specimens was conducted...
February 20, 2018: Chinese Medical Journal
https://www.readbyqxmd.com/read/29449811/hdac6-inhibition-promotes-transcription-factor-eb-activation-and-is-protective-in-experimental-kidney-disease
#10
Angela S Brijmohan, Sri N Batchu, Syamantak Majumder, Tamadher A Alghamdi, Karina Thieme, Sarah McGaugh, Youan Liu, Suzanne L Advani, Bridgit B Bowskill, M Golam Kabir, Laurette Geldenhuys, Ferhan S Siddiqi, Andrew Advani
To contend with the deleterious effects of accumulating misfolded protein aggregates or damaged organelles cells rely on a system of quality control processes, among them the autophagy-lysosome pathway. This pathway is itself controlled by a master regulator transcription factor termed transcription factor EB (TFEB). When TFEB localizes to the cell nucleus it promotes the expression of a number of genes involved in protein clearance. Here, we set out to determine (1) whether TFEB expression is altered in chronic kidney disease (CKD); (2) whether inhibition of the cytosolic deacetylase histone deacetylase 6 (HDAC6) affects TFEB acetylation and nuclear localization; and (3) whether HDAC6 inhibition, in turn, alters the natural history of experimental CKD...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29449653/cftr-mutation-enhances-dishevelled-degradation-and-results-in-impairment-of-wnt-dependent-hematopoiesis
#11
Huaqin Sun, Yan Wang, Jieting Zhang, Yan Chen, Yanyan Liu, Ziyuan Lin, Mingfeng Liu, Kai Sheng, Huijuan Liao, Kam Sze Tsang, Xiaohu Zhang, Xiaohua Jiang, Wenming Xu, Meng Mao, Hsiao Chang Chan
Mutations of cystic fibrosis transmembrane conductance regulator (CFTR) cause cystic fibrosis (CF) with a multitude of clinical manifestations. Some CF patients develop clinically significant anemia, suggesting that CFTR may regulate hematopoiesis. Here, we report that cftr mutant zebrafish model exhibits primitive and definitive hematopoietic defects with impaired Wnt signaling. Cftr is found to interact, via its PDZ-binding domain (PDZBD), with Dishevelled (Dvl), a key component of Wnt signaling required for hematopoietic progenitor specification, thus protecting Dvl from Dapper1 (Dpr1)-induced lysosomal degradation...
February 15, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29449316/snareing-an-arp-requires-a-lir
#12
Sharon A Tooze
The fusion of autophagosomes with lysosomes is an obligatory step in the self-eating process of autophagy. In this issue, Kumar et al. (2018. J. Cell Biol. https://doi.org/10.1083/jcb.201708039) identify a protein complex, the autophagosome recognition particle (ARP), that chaperones a key SNARE, syntaxin 17, to the autophagosome membrane. Intriguingly, this protein complex coordinates both delivery and membrane insertion as a prelude to fusion.
February 15, 2018: Journal of Cell Biology
https://www.readbyqxmd.com/read/29448933/the-curious-case-of-vacuolar-atpase-regulation-of-signaling-pathways
#13
REVIEW
Sahithi Pamarthy, Arpita Kulshrestha, Gajendra K Katara, Kenneth D Beaman
The Vacuolar ATPase (V-ATPase) is a proton pump responsible for controlling the intracellular and extracellular pH of cells. The structure of V-ATPase has been highly conserved among all eukaryotic cells and is involved in diverse functions across species. V-ATPase is best known for its acidification of endosomes and lysosomes and is also important for luminal acidification of specialized cells. Several reports have suggested the involvement of V-ATPase in maintaining an alkaline intracellular and acidic extracellular pH thereby aiding in proliferation and metastasis of cancer cells respectively...
February 15, 2018: Molecular Cancer
https://www.readbyqxmd.com/read/29447902/the-erythrocyte-osmotic-resistance-test-as-screening-tool-for-cholesterol-related-lysosomal-storage-diseases
#14
Laura López de Frutos, Jorge J Cebolla, Pilar Irún, Ralf Köhler, Pilar Giraldo
BACKGROUND: Erythrocyte volume regulation and membrane elasticity are essential for adaptation to osmotic and mechanical stress, and life span. Here, we evaluated whether defective cholesterol trafficking caused by the rare lysosomal storages diseases (LSDs), Niemann-Pick type C (NPC) and Lysosomal acid lipase (LAL) deficiency (LALD) impairs these properties. Moreover, we tested whether measurements of cholesterol membrane content and osmotic resistance serve as a screening test for these LSDs...
February 12, 2018: Clinica Chimica Acta; International Journal of Clinical Chemistry
https://www.readbyqxmd.com/read/29446751/molecular-mechanism-to-target-the-endosomal-mon1-ccz1-gef-complex-to-the-pre-autophagosomal-structure
#15
Jieqiong Gao, Lars Langemeyer, Daniel Kuemmel, Fulvio Reggiori, Christian Ungermann
During autophagy, a newly formed double membrane surrounds its cargo to generate the so-called autophagosome, which then fuses with a lysosome after closure. Previous work implicated that endosomal Rab7/Ypt7 associates to autophagosomes prior to their fusion with lysosomes. Here, we unravel how the Mon1-Ccz1 guanosine exchange factor (GEF) acting upstream of Ypt7 is specifically recruited to the pre-autophagosomal structure under starvation conditions. We find that Mon1-Ccz1 directly binds to Atg8, the yeast homolog of the members of the mammalian LC3 protein family...
February 15, 2018: ELife
https://www.readbyqxmd.com/read/29446631/mechanistic-investigation-and-multiplexing-of-liposome-assisted-metabolic-glycan-labeling
#16
Yuting Sun, Senlian Hong, Ran Xie, Rongbing Huang, Ruoxing Lei, Bo Cheng, Deen Sun, Yifei Du, Corwin M Nycholat, James C Paulson, Xing Chen
Metabolic labeling of glycans with bioorthogonal reporters has been widely used for glycan imaging and glycoproteomic profiling. One of the intrinsic limitations of metabolic glycan labeling is the lack of cell-type selectivity. The recently developed liposome-assisted bioorthogonal reporter (LABOR) strategy provides a promising means to overcome this limitation, but the mechanism of LABOR has not been investigated in detail. In this work, we performed a mechanistic study on LABOR and explored its multiplexing capability...
February 15, 2018: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/29446145/neuronal-ceroid-lipofuscinosis-in-salukis-is-caused-by-a-single-base-pair-insertion-in-cln8
#17
F Lingaas, O-A Guttersrud, E Arnet, A Espenes
Neuronal ceroid lipofuscinoses (NCLs) are heterogenic inherited lysosomal storage diseases that have been described in a number of species including humans, sheep, cattle, cats and a number of different dog breeds, including Salukis. Here we present a novel genetic variant associated with the disease in this particular breed of dog. In a clinical case, a Saluki developed progressive neurological signs, including disorientation, anxiety, difficulties in eating, seizures and loss of vision, and for welfare reasons, was euthanized at 22 months of age...
February 2018: Animal Genetics
https://www.readbyqxmd.com/read/29446030/slow-progression-of-renal-failure-in-a-child-with-infantile-cystinosis
#18
Maria Bitsori, Eleni Vergadi, Emmanouil Galanakis
Cystinosis is a rare autosomal recessive lysosomal transport disorder, characterized by the accumulation of the aminoacid cystine and progressive dysfunction of several organs. Kidneys are severely affected, and the most frequent form, infantile nephropathic cystinosis, presents with growth failure in infancy, renal Fanconi syndrome and end-stage renal disease by the first decade of life. We report of a girl with infantile nephropathic cystinosis that has reached adolescence without the need of renal replacement therapy and without extrarenal manifestations despite her delayed diagnosis and treatment initiation...
February 14, 2018: CEN Case Reports
https://www.readbyqxmd.com/read/29445291/raptor-mediates-the-antiproliferation-of-cardamonin-by-mtorc1-inhibition-in-skov3-cells
#19
Daohua Shi, Yanting Zhu, Peiguang Niu, Jintuo Zhou, Huajiao Chen
Purpose: Cardamonin inhibits the proliferation of SKOV3 cells by suppressing the mammalian target of rapamycin complex 1 (mTORC1). However, the mechanism of cardamonin on mTORC1 inhibition has not been well demonstrated. The regulatory-associated protein of TOR (Raptor) is an essential component of mTORC1. Here, we investigated the role of Raptor in the mTORC1 inhibition effect of cardamonin in SKOV3 cells. Methods: The expression of Raptor was knockdown by small interfering RNA (siRNA)...
2018: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29445175/a-novel-autophagy-inhibitor-berbamine-blocks-snare-mediated-autophagosome-lysosome-fusion-through-upregulation-of-bnip3
#20
Ruoqiu Fu, Qin Deng, Hongwei Zhang, Xiaoye Hu, Yunong Li, Yanxia Liu, Jinjiao Hu, Qingsong Luo, Yanhao Zhang, Xiuxing Jiang, Lirong Li, Chong Yang, Ning Gao
Increasing evidences reveal that autophagy inhibitor could enhance the effect of chemotherapy to cancer. However, few autophagy inhibitors are currently approved for clinical application in humans. Berbamine (BBM) is a natural compound extracted from traditional Chinese medicine that is widely used for treatment of a variety of diseases without any obvious side effects. Here we found that BBM is a novel auophagy inhibitor, which potently induced the accumulation of autophagosomes by inhibiting autophagosome-lysosome fusion in human breast cancer cells...
February 14, 2018: Cell Death & Disease
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