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Selective autophagy

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https://www.readbyqxmd.com/read/28647372/delta-opioid-receptor-agonist-attenuates-lipopolysaccharide-induced-myocardial-injury-by-regulating-autophagy
#1
Pin Zhao, Jianke Kuai, Jinjian Gao, Li Sun, Yan Wang, Linong Yao
BACKGROUND: Previous studies have described the protective effects of DADLE on myocardial injury in sepsis. Recently, autophagy has been shown to be an innate defense mechanism in sepsis-related myocardial injury. However, whether DADLE has an pro-autophagic effect is yet to be elucidated. The present study aimed to investigate the effect of DADLE on the regulation of autophagy during sepsis. METHODS: Male mice were subjected to LPS or vehicle intraperitoneal injection...
June 21, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28642198/treatment-of-intestinal-fibrosis-in-experimental-inflammatory-bowel-disease-by-the-pleiotropic-actions-of-a-local-rho-kinase-inhibitor
#2
Tom Holvoet, Sarah Devriese, Karolien Castermans, Sandro Boland, Dirk Leysen, Yves-Paul Vandewynckel, Lindsey Devisscher, Lien Van den Bossche, Sophie Van Welden, Melissa Dullaers, Roosmarijn E Vandenbroucke, Riet De Rycke, Karel Geboes, Arnaud Bourin, Olivier Defert, Pieter Hindryckx, Martine De Vos, Debby Laukens
BACKGROUND: Intestinal fibrosis resulting in (sub)obstruction is a common complication of Crohn's disease (CD). Rho kinases (ROCKs) play multiple roles in TGFβ1-induced myofibroblast activation that could be therapeutic targets. Because systemic ROCK inhibition causes cardiovascular side-effects, we evaluated the effects of a locally acting ROCK inhibitor (AMA0825) on intestinal fibrosis. METHODS: Fibrosis was assessed in mouse models using dextran sulfate sodium and adoptive T cell transfer...
June 19, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28642035/improving-the-efficacy-of-hormone-therapy-in-breast-cancer-the-role-ofcholesterol-metabolism-in-serm-mediated-autophagy-cell-differentiation-and-death
#3
REVIEW
Julie Leignadier, Florence Dalenc, Marc Poirot, Sandrine Silvente-Poirot
Breast cancer (BC) is one of the most common female cancers in the world, with estrogen receptor (ER)-positive BC the most frequent subtype. Tamoxifen (Tam) is an effective drug that competitively binds to the ER and is routinely used for the treatment of ER-positive BC. However, a number of ER-positive BC do not respond to Tam treatment and acquired resistance is often observed, constituting a major challenge for extending patient life expectancy. The mechanisms responsible for these treatment failures remain unclear, indicating the requirement for other targets and better predictors for patient response to Tam...
June 19, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28642033/atg4b-inhibitors-with-a-benzotropolone-core-structure-block-autophagy-and-augment-efficiency-of-chemotherapy-in-mice
#4
Ammar Kurdi, Matthias Cleenewerck, Christel Vangestel, Sophie Lyssens, Wim Declercq, Jean-Pierre Timmermans, Sigrid Stroobants, Koen Augustyns, Guido R Y De Meyer, Pieter Van Der Veken, Wim Martinet
Autophagy is a cell survival mechanism hijacked by advanced tumors to endure a rough microenvironment. Late autophagy inhibitors such as (hydroxy)chloroquine have been used clinically to halt tumor progression with modest success. However, given the toxic nature of these compounds and their lack of specificity, novel targets should be considered. We recently identified a benzotropolone derivative that significantly inhibited the essential autophagy protein ATG4B. Therefore, we synthesized and tested additional benzotropolone compounds to identify a promising ATG4B inhibitor that impairs autophagy both in vitro and in vivo...
June 19, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28637020/autophagy-related-genes-are-induced-by-histone-deacetylase-inhibitor-suberoylanilide-hydroxamic-acid-via-the-activation-of-cathepsin-b-in-human-breast-cancer-cells
#5
Han Han, Jing Li, Xiuyan Feng, Hui Zhou, Shanchun Guo, Weiqiang Zhou
Autophagy is involved in modulating tumor cell motility and invasion, resistance to epithelial-to-mesenchymal transition, anoikis, and escape from immune surveillance. We have previous shown that SAHA is capable to induce several apoptosis and autophagy-related gene expression in breast cancers. However, the exact mechanisms of autophagy activation in this context have not been fully identified. Our results showed that the expression and the activity of Cathepsin B (CTSB), one of the major lysosomal cysteine proteases, were significantly increased in MDA-MB- 231 and MCF-7 cells upon SAHA treatment...
June 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28633985/autophagy-a-double-edged-sword-to-fight-plant-viruses
#6
Marion Clavel, Simon Michaeli, Pascal Genschik
In metazoans, autophagy is an essential component of host defense against viruses, orchestrating their degradation. Such antiviral functions for autophagy have also been long suspected in the green lineage. Two recent reports provide molecular insights on how plants selectively send viral proteins and even particles to the vacuole.
June 17, 2017: Trends in Plant Science
https://www.readbyqxmd.com/read/28627726/the-arl3-and-arl1-gtpase-cooperates-with-cog8-to-regulate-selective-autophagy-via-atg9-trafficking
#7
I-Hao Wang, Yi-Jie Chen, Jia-Wei Hsu, Fang-Jen S Lee
The Arl3-Arl1 GTPase cascade plays important roles in vesicle trafficking at the late Golgi and endosomes. Subunits of the conserved oligomeric Golgi (COG) complex, a tethering factor, are important for endosome-to-Golgi transport and contribute to the efficient functioning of the cytoplasm-to-vacuole (Cvt) pathway, a well-known selective autophagy pathway. According to our findings, the Arl3-Arl1 GTPase cascade cooperates with Cog8 to regulate the Cvt pathway via Atg9 trafficking. arl3cog8Δ and arl1cog8Δ exhibit profound defects in aminopeptidase I maturation in rich medium...
June 19, 2017: Traffic
https://www.readbyqxmd.com/read/28626500/mitophagy-transcriptome-mechanistic-insights-into-polyphenol-mediated-mitophagy
#8
REVIEW
Sijie Tan, Esther Wong
Mitochondria are important bioenergetic and signalling hubs critical for myriad cellular functions and homeostasis. Dysfunction in mitochondria is a central theme in aging and diseases. Mitophagy, a process whereby damaged mitochondria are selectively removed by autophagy, plays a key homeostatic role in mitochondrial quality control. Upregulation of mitophagy has shown to mitigate superfluous mitochondrial accumulation and toxicity to safeguard mitochondrial fitness. Hence, mitophagy is a viable target to promote longevity and prevent age-related pathologies...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28622300/the-als-linked-e102q-mutation-in-sigma-receptor-1-leads-to-er-stress-mediated-defects-in-protein-homeostasis-and-dysregulation-of-rna-binding-proteins
#9
Alice Dreser, Jan Tilmann Vollrath, Antonio Sechi, Sonja Johann, Andreas Roos, Alfred Yamoah, Istvan Katona, Saeed Bohlega, Dominik Wiemuth, Yuemin Tian, Axel Schmidt, Jörg Vervoorts, Marc Dohmen, Cordian Beyer, Jasper Anink, Eleonora Aronica, Dirk Troost, Joachim Weis, Anand Goswami
Amyotrophic lateral sclerosis (ALS) is characterized by the selective degeneration of motor neurons (MNs) and their target muscles. Misfolded proteins which often form intracellular aggregates are a pathological hallmark of ALS. Disruption of the functional interplay between protein degradation (ubiquitin proteasome system and autophagy) and RNA-binding protein homeostasis has recently been suggested as an integrated model that merges several ALS-associated proteins into a common pathophysiological pathway...
June 16, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28619261/sequestosome-1-sqstm1-p62-maintains-protein-folding-capacity-under-endoplasmic-reticulum-stress-in-mouse-hypothalamic-organotypic-culture
#10
Takashi Tominaga, Motomitsu Goto, Takeshi Onoue, Akira Mizoguchi, Mariko Sugiyama, Taku Tsunekawa, Daisuke Hagiwara, Yoshiaki Morishita, Yoshihiro Ito, Shintaro Iwama, Hidetaka Suga, Ryoichi Banno, Hiroshi Arima
Sequestosome 1 (SQSTM1) also known as ubiquitin-binding protein p62 (p62) is a cargo protein involved in the degradation of misfolded proteins via selective autophagy. Disruption of autophagy and resulting accumulation of misfolded proteins in the endoplasmic reticulum (ER) leads to ER stress. ER stress is implicated in several neurodegenerative diseases and obesity. As knockout of p62 (p62KO) reportedly induces obesity in mice, we examined how p62 contributes to ER stress and the ensuing unfolded protein response (UPR) in hypothalamus using mouse organotypic cultures in the present study...
June 12, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28618992/modulating-mitophagy-in-mitochondrial-disease
#11
Eszter Dombi, Heather Mortiboys, Joanna Poulton
Mitochondrial diseases may result from mutations in the maternally-inherited mitochondrial DNA (mtDNA) or from mutations in nuclear genes encoding mitochondrial proteins. Their bi-genomic nature makes mitochondrial diseases a very heterogeneous group of disorders that can present at any age and can affect any type of tissue. The autophagic-lysosomal degradation pathway plays an important role in clearing dysfunctional and redundant mitochondria through a specific quality control mechanism termed mitophagy. Mitochondria could be targeted for autophagic degradation for a variety of reasons including basal turnover for recycling, starvation induced degradation, and degradation due to damage...
June 16, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28617998/schwann-cell-specific-deletion-of-the-endosomal-pi-3-kinase-vps34-leads-to-delayed-radial-sorting-of-axons-arrested-myelination-and-abnormal-erbb2-erbb3-tyrosine-kinase-signaling
#12
Anne M Logan, Anna E Mammel, Danielle C Robinson, Andrea L Chin, Alec F Condon, Fred L Robinson
The PI 3-kinase Vps34 (Pik3c3) synthesizes phosphatidylinositol 3-phosphate (PI3P), a lipid critical for both endosomal membrane traffic and macroautophagy. Human genetics have implicated PI3P dysregulation, and endosomal trafficking in general, as a recurring cause of demyelinating Charcot-Marie-Tooth (CMT) peripheral neuropathy. Here, we investigated the role of Vps34, and PI3P, in mouse Schwann cells by selectively deleting Vps34 in this cell type. Vps34-Schwann cell knockout (Vps34(SCKO) ) mice show severe hypomyelination in peripheral nerves...
June 15, 2017: Glia
https://www.readbyqxmd.com/read/28617241/full-length-rtn3-regulates-turnover-of-tubular-endoplasmic-reticulum-via-selective-autophagy
#13
Paolo Grumati, Giulio Morozzi, Soraya Hölper, Muriel Mari, Marie-Lena Ie Harwardt, Riqiang Yan, Stefan Müller, Fulvio Reggiori, Mike Heilemann, Ivan Dikic
The turnover of endoplasmic reticulum (ER) ensures the correct biological activity of its distinct domains. In mammalian cells the ER is degraded via a selective autophagy pathway (ER-phagy), mediated by two specific receptors: FAM134B, responsible for the turnover of ER sheets and SEC62 that regulates ER recovery following stress. Here we identified reticulon 3 (RTN3) as a specific receptor for the degradation of ER tubules. Oligomerization of the long isoform of RTN3 is sufficient to trigger fragmentation of ER tubules...
June 15, 2017: ELife
https://www.readbyqxmd.com/read/28615727/oestrogen-inhibits-arterial-calcification-by-promoting-autophagy
#14
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/28614778/the-human-immunodeficiency-virus-hiv1-protease-inhibitor-sanquinavir-activates-autophagy-and-removes-lipids-deposited-in-lipid-droplets
#15
A Polus, M Bociaga-Jasik, U Czech, J Goralska, U Cialowicz, M Chojnacka, M Polus, K Jurowski, A Dembinska-Kiec
Reduction in mortality and increased average life span of the human immunodeficiency virus (HIV)-infected patients treated with antiretroviral therapy (ART) are associated with the risk of unwanted effects, such as insulin resistance and dyslipidemia with cardiovascular complications. Antiretroviral therapy may also be associated with lipodystrophy characterized as peripheral lipoatrophy with central fat accumulation. Understanding the molecular mechanisms of lipodystrophy caused by ART is important for therapeutic strategy and the prediction of side-effects...
April 2017: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
https://www.readbyqxmd.com/read/28614042/bnip3l-nix-dependent-mitophagy-regulates-cell-differentiation-via-metabolic-reprogramming
#16
Lorena Esteban-Martínez, Patricia Boya
Macroautophagy/autophagy is the process by which cellular components are degraded and recycled within the lysosome. These components include mitochondria, the selective degradation of which is known as mitophagy. Mitochondria are dynamic organelles that constantly adapt their morphology, function, and number to accommodate the metabolic needs of the cell. Extensive metabolic reconfiguration occurs during cell differentiation, when mitochondrial activity increases in most cell types. However, our data demonstrate that during physiological retinal ganglion cell (RGC) development, mitophagy-dependent metabolic reprogramming towards glycolysis regulates numbers of RGCs, which are the first neurons to differentiate in the retina and whose axons form the optic nerve...
June 14, 2017: Autophagy
https://www.readbyqxmd.com/read/28614034/sqstm1-p62-sequestosome-1-senses-cellular-ubiquitin-stress-through-e2-mediated-ubiquitination
#17
Jiao Yang, Hong Peng, Xiaoduo Xie, Ronggui Hu
The alterations in cellular ubiquitin (Ub) homeostasis, known as Ub stress, feature and affect cellular responses in multiple conditions, yet the underlying mechanisms are incompletely understood. We recently report that the macroautophagy/autophagy receptor SQSTM1/p62, functions as a novel Ub sensor to activate autophagy upon Ub(+) stress (upregulation of the Ub level). First, SQSTM1 was found to undergo extensive ubiquitination and activate autophagy under Ub(+) stress induced by prolonged Bortezomib (BTZ) treatment, Ub overexpression or by heat shock...
June 14, 2017: Autophagy
https://www.readbyqxmd.com/read/28610619/amyotrophic-lateral-sclerosis-patient-ipsc-derived-astrocytes-impair-autophagy-via-non-cell-autonomous-mechanisms
#18
Martin Madill, Katya McDonagh, Jun Ma, Alice Vajda, Paul McLoughlin, Timothy O'Brien, Orla Hardiman, Sanbing Shen
Amyotrophic lateral sclerosis, a devastating neurodegenerative disease, is characterized by the progressive loss of motor neurons and the accumulation of misfolded protein aggregates. The latter suggests impaired proteostasis may be a key factor in disease pathogenesis, though the underlying mechanisms leading to the accumulation of aggregates is unclear. Further, recent studies have indicated that motor neuron cell death may be mediated by astrocytes. Herein we demonstrate that ALS patient iPSC-derived astrocytes modulate the autophagy pathway in a non-cell autonomous manner...
June 13, 2017: Molecular Brain
https://www.readbyqxmd.com/read/28606244/-mitophagy-and-nervous-system-disease
#19
Ming-Xi Li, De-Zhi Mu
Mitophagy is a process during which the cell selectively removes the mitochondria via the mechanism of autophagy. It is crucial to the functional completeness of the whole mitochondrial network and determines cell survival and death. On the one hand, the damaged mitochondria releases pro-apoptotic factors which induce cell apoptosis; on the other hand, the damaged mitochondria eliminates itself via autophagy, which helps to maintain cell viability. Mitophagy is of vital importance for the development and function of the nervous system...
June 2017: Zhongguo Dang Dai Er Ke za Zhi, Chinese Journal of Contemporary Pediatrics
https://www.readbyqxmd.com/read/28598976/the-dynamic-role-of-autophagy-and-mapk-signaling-in-determining-cell-fate-under-cisplatin-stress-in-osteosarcoma-cells
#20
Sudeshna Mukherjee, Subhra Dash, K Lohitesh, Rajdeep Chowdhury
Osteosarcoma (OS) is an aggressive bone malignancy commonly observed in children and adolescents. Sub-optimal therapy for years has irretrievably compromised the chances of OS patient survival; also, lack of extensive research on this rare disease has hindered therapeutic development. Cisplatin, a common anti-tumor drug, is currently an integral part of treatment regime for OS along with methotrexate and doxorubicin. However, toxicity issues associated with combination module impede OS therapy. Also, despite the proven benefits of cisplatin, acquisition of resistance remains a concern with cisplatin-based therapy...
2017: PloS One
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