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https://www.readbyqxmd.com/read/28548902/er-mitochondria-signaling-regulates-autophagy
#1
Patricia Gomez-Suaga, Sebastien Paillusson, Christopher C J Miller
The endoplasmic reticulum (ER) and mitochondria form tight functional contacts that regulate a number of key cellular processes. The formation of these contacts involves "tethering proteins" that function to recruit regions of ER to mitochondria. The integral ER protein VAPB (VAMP associated protein B and C) binds to the outer mitochondrial membrane protein, RMDN3/PTPIP51 (regulator of microtubule dynamics 3) to form one such set of tethers. Recently, we showed that the VAPB-RMDN3 tethers regulate macroautophagy/autophagy...
May 26, 2017: Autophagy
https://www.readbyqxmd.com/read/28548877/role-of-osgin1-in-mediating-smoking-induced-autophagy-in-the-human-airway-epithelium
#2
Guoqing Wang, Haixia Zhou, Yael Strulovici-Barel, Mohammed Al-Hijji, Xuemei Ou, Jacqueline Salit, Matthew S Walters, Michelle R Staudt, Robert J Kaner, Ronald G Crystal
Enhanced macroautophagy/autophagy is recognized as a component of the pathogenesis of smoking-induced airway disease. Based on the knowledge that enhanced autophagy is linked to oxidative stress and the DNA damage response, both of which are linked to smoking, we used microarray analysis of the airway epithelium to identify smoking upregulated genes known to respond to oxidative stress and the DNA damage response. This analysis identified OSGIN1 (oxidative stress induced growth inhibitor 1) as significantly upregulated by smoking, in both the large and small airway epithelium, an observation confirmed by an independent small airway microarray cohort, TaqMan PCR of large and small airway samples and RNA-Seq of small airway samples...
May 26, 2017: Autophagy
https://www.readbyqxmd.com/read/28545464/c10orf10-depp-mediated-ros-accumulation-is-a-critical-modulator-of-foxo3-induced-autophagy
#3
S Salcher, M Hermann, U Kiechl-Kohlendorfer, M J Ausserlechner, P Obexer
BACKGROUND: Neuroblastoma is the most common solid tumor in childhood and develops from undifferentiated progenitor cells of the sympathetic nervous system. In neuronal tumor cells DNA-damaging chemotherapeutic agents activate the transcription factor FOXO3 which regulates the formation of reactive oxygen species (ROS) and cell death as well as a longevity program associated with therapy resistance. We demonstrated before that C10ORF10/DEPP, a transcriptional target of FOXO3, localizes to peroxisomes and mitochondria and impairs cellular ROS detoxification...
May 25, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/28544790/roles-of-autophagy-and-endoplasmic-reticulum-stress-in-intracerebral-hemorrhage-induced-secondary-brain-injury-in%C3%A2-rats
#4
Xiao-Chun Duan, Wei Wang, Dong-Xia Feng, Jia Yin, Gang Zuo, Dong-Dong Chen, Zhou-Qing Chen, Hai-Ying Li, Zhong Wang, Gang Chen
OBJECTIVES: This study aimed to evaluate the roles of autophagy and endoplasmic reticulum (ER) stress in intracerebral hemorrhage (ICH)-induced secondary brain injury (SBI) in rats. METHODS: Autophagy inducer (rapamycin) and inhibitor (3-methyladenine), as well as ER stress activator (tunicamycin, TM) and inhibitor (tauroursodeoxycholic acid, TUDCA), were used. Bafilomycin A1, an inhibitor of autophagosome-lysosome fusion, was used to assess autophagic flux. RESULTS: Autophagy and ER stress were enhanced in the week after ICH...
May 19, 2017: CNS Neuroscience & Therapeutics
https://www.readbyqxmd.com/read/28544137/phenotypic-identification-of-a-novel-autophagy-inhibitor-chemotype-targeting-lipid-kinase-vps34
#5
Herbert Waldmann, Lucas Robke, Luca Laraia, Marjorie A Carnero Corrales, Georgios Konstantinidis, Makoto Muroi, André Richters, Michael Winzker, Tobias Engbring, Stefano Tomassi, Nobumoto Watanabe, Hiroyuki Osada, Daniel Rauh, Yaowen Wu, Julian Engel
Autophagy is a critical regulator of cellular homeostasis and metabolism. Interference with this process is considered a new approach for the treatment of disease, in particular cancer and neurological disorders. Therefore, novel small molecule autophagy modulators are in high demand. We describe the discovery of autophinib, a potent autophagy inhibitor with a novel chemotype. Autophinib was identified by means of a phenotypic assay monitoring formation of autophagy-induced puncta indicating accumulation of lipidated cytosolic protein LC3 on the autophagosomal membrane...
May 22, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28542134/phosphorylated-cav1-activates-autophagy-through-an-interaction-with-becn1-under-oxidative-stress
#6
Jihoon Nah, Seung-Min Yoo, Sunmin Jung, Eun Il Jeong, Moonju Park, Bong-Kiun Kaang, Yong-Keun Jung
CAV1/Caveolin1, an integral membrane protein, is involved in caveolae function and cellular signaling pathways. Here, we report that CAV1 is a positive regulator of autophagy under oxidative stress and cerebral ischemic injury. Treatment with hydrogen peroxide enhanced autophagy flux and caused the localization of BECN1 to the mitochondria, whereas these changes were impaired in the absence of CAV1. Among many autophagy signals, only LC3 foci formation in response to hydrogen peroxide was abolished by CAV1 deficiency...
May 25, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28539405/tumor-susceptibility-gene-101-tsg101-regulates-predisposition-towards-apoptosis-via-escrt-machinery-accessory-proteins
#7
Zenia Kaul, Oishee Chakrabarti
ESCRT proteins are implicated in myriad cellular processes, including endosome formation, fusion of autophagosomes/amphisomes with lysosomes and apoptosis. The role played by these proteins in either facilitating or protecting against apoptosis is still unclear. In this study, while trying to understand how deficiency of Mahogunin RING Finger 1 (MGRN1) affects cell viability, we uncover a novel role for its interactor, the ESCRT-I protein, TSG101 - it directly participates in mitigating ER stress mediated apoptosis...
May 24, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28538438/differential-regulation-of-the-autophagy-and-proteasome-pathways-in-skeletal-muscles-in-sepsis
#8
Flavia Stana, Marija Vujovic, Dominique Mayaki, Jean-Philippe Leduc-Gaudet, Philippe Leblanc, Laurent Huck, Sabah N A Hussain
OBJECTIVES: Skeletal muscle fiber atrophy develops in response to severe sepsis, but it is unclear as to how the proteolytic pathways that are involved in its development are differentially regulated. We investigated the link between sepsis-induced fiber atrophy and activation of the proteasome and autophagy pathways and whether the degree of activation is more severe and sustained in limb muscles than it is in the diaphragm. DESIGN: Randomized controlled experiment...
May 22, 2017: Critical Care Medicine
https://www.readbyqxmd.com/read/28537930/3-decylcatechol-induces-autophagy-mediated-cell-death-through-the-ire1%C3%AE-jnk-p62-in-hepatocellular-carcinoma-cells
#9
Da-Hye Go, Yu Geon Lee, Da-Hye Lee, Jin-A Kim, In-Hwa Jo, Yeon Soo Han, Yong Hun Jo, Kwang-Youn Kim, Young-Kyo Seo, Jae-Hak Moon, Chang Hwa Jung, Tae-Il Jeon
The natural, phenolic lipid urushiol exhibits both antioxidant and anticancer activities; however, its biological activity on hepatocellular carcinoma (HCC) has not been previously investigated. Here, we demonstrate that an urushiol derivative, 3-decylcatechol (DC), induces human HCC Huh7 cell death by induction of autophagy. DC initiates the autophagic process by activation of the mammalian target of rapamycin signaling pathway via Unc-51-like autophagy activating kinase 1, leading to autophagosome formation...
May 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28537890/protective-effect-of-madecassoside-on-h2o2-induced-oxidative-stress-and-autophagy-activation-in-human-melanocytes
#10
Yuting Ling, Qingli Gong, Xixi Xiong, Li Sun, Wene Zhao, Wenyuan Zhu, Yan Lu
BACKGROUND: Centella asiatica (L.) Urb. is a traditional Chinese medicine that has many medical applications, including wound healing and anti-oxidation. Some traditional Chinese Medicine doctors have found that it has therapeutic effects for external use in the repigmentation of vitiligo and post-inflammatory hypopigmentation. This study was designed to evaluate the effects of madecassoside, a major bioactive component of C. asiatica, on oxidative stress in human melanocytes and its possible mechanism of action...
May 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28537760/caveolin-1-autophagy-pathway-mediated-cardiomyocyte-hypertrophy-induced-by-apelin-13
#11
Di Wu, Feng Xie, Ling Xiao, Fen Feng, Shifang Huang, Lu He, Meiqing Liu, Qun Zhou, Lanfang Li, Linxi Chen
Apelin, an endogenous ligand for apelin receptor (APJ), is reported to be involved in cardiomyocyte hypertrophy. In this study, we explored the mechanism of cardiomyocyte hypertrophy induced by apelin-13/APJ system. Left ventricular hypertrophy (LVH) rat model was established by constricting the abdominal aorta. Western blots were used for protein expression in LVH rats and cultured H9c2 cardiomyocytes. Transmission electron microscopy (TEM) was used to monitor morphological features of cells. In addition, the diameter and volume of H9c2 cells were detected by Scepter™ Handheld Automated Cell Counter...
May 24, 2017: DNA and Cell Biology
https://www.readbyqxmd.com/read/28537658/research-on-the-relationship-between-artesunate-and-raji-cell-autophagy-and-apoptosis-of-burkitt-s-lymphoma-and-its-mechanism
#12
Z-C Wang, Y Liu, H Wang, Q-K Han, C Lu
OBJECTIVE: To investigate the effects of Artesunate (ART) on the Raji cell proliferation, apoptosis and autophagy with Raji cells of Burkitt's lymphoma as the objects of study, and to investigate the anti-tumor mechanism of ART. MATERIALS AND METHODS: Morphological examinations of apoptotic and autophagy were performed. MTT assay was used to detect the cell proliferation after ART treatment. The changes in cell apoptosis and cell cycle were detected by flow cytometer...
May 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28537477/atg-conjugation-dependent-degradation-of-the-inner-autophagosomal-membrane-is-a-key-step-for-autophagosome-maturation
#13
Ikuko Koyama-Honda, Kotaro Tsuboyama, Noboru Mizushima
Although the autophagy-related (ATG) conjugation systems are thought to be important for a late step of autophagosome formation, their precise function has been poorly understood because they are also required for localization of the most important autophagosomal marker LC3. In our recent study we found that, using the autophagosomal SNARE STX17 (syntaxin 17) as an alternative marker, autophagosome-like structures were generated in ATG conjugation system-deficient cells. Those structures could fuse with lysosomes but the degradation of the inner autophagosomal membrane was significantly delayed...
May 24, 2017: Autophagy
https://www.readbyqxmd.com/read/28536471/caffeic-acid-attenuates-diabetic-kidney-disease-via-modulation-of-autophagy-in-a-high-fat-diet-streptozotocin-induced-diabetic-rat
#14
Marwa Matboli, Sanaa Eissa, Doaa Ibrahim, Marwa G A Hegazy, Shalabia S Imam, Eman K Habib
The aim of this study is to evaluate the anti-diabetic nephropathy effect of Caffeic acid and to prove our hypothesis for its mechanism of action that it may occur by reactivation of autophagy pathway via suppression of autophagy regulatory miRNAs. In vivo, high-fat diet and streptozotocin-induced (HFD-STZ) diabetic rats were treated with Caffeic acid once per day for 12 weeks before and after development of diabetic nephropathy. Blood and urine biochemical parameters, autophagy transcripts and their epigenetic regulators together with renal tissue morphology were investigated...
May 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28534814/autophagy-regulates-proteasome-inhibitor-induced-pigmentation-in-human-embryonic-stem-cell-derived-retinal-pigment-epithelial-cells
#15
Kati Juuti-Uusitalo, Ali Koskela, Niko Kivinen, Johanna Viiri, Juha M T Hyttinen, Mika Reinisalo, Arto Koistinen, Hannu Uusitalo, Debasish Sinha, Heli Skottman, Kai Kaarniranta
The impairment of autophagic and proteasomal cleansing together with changes in pigmentation has been documented in retinal pigment epithelial (RPE) cell degeneration. However, the function and co-operation of these mechanisms in melanosome-containing RPE cells is still unclear. We show that inhibition of proteasomal degradation with MG-132 or autophagy with bafilomycin A1 increased the accumulation of premelanosomes and autophagic structures in human embryonic stem cell (hESC)-derived RPE cells. Consequently, upregulation of the autophagy marker p62 (also known as sequestosome-1, SQSTM1) was confirmed in Western blot and perinuclear staining...
May 19, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28534010/autophagy-in-the-placenta
#16
REVIEW
Soo-Young Oh, Cheong-Rae Roh
Autophagy is an evolutionarily conserved catalytic process by which cytoplasmic components including damaged macromolecules and organelles are degraded. The role of autophagy includes adaptive responses to nutrition deprivation or intracellular stimuli. Although autophagosomes were first observed in early 1960s, it was 1990s that autophagy-related genes in yeast were identified and studied. Nowadays, the molecular machinery of autophagy and signaling pathway to various stimuli are almost outlined. Dysregulation of autophagic activity has been implicated in many human diseases including neurodegenerative diseases, infection and inflammation, and malignancies...
May 2017: Obstetrics & Gynecology Science
https://www.readbyqxmd.com/read/28533369/phosphorylated-presenilin-1-decreases-%C3%AE-amyloid-by-facilitating-autophagosome-lysosome-fusion
#17
Victor Bustos, Maria V Pulina, Ashley Bispo, Alison Lam, Marc Flajolet, Fred S Gorelick, Paul Greengard
Presenilin 1 (PS1), the catalytic subunit of the γ-secretase complex, cleaves βCTF to produce Aβ. We have shown that PS1 regulates Aβ levels by a unique bifunctional mechanism. In addition to its known role as the catalytic subunit of the γ-secretase complex, selective phosphorylation of PS1 on Ser367 decreases Aβ levels by increasing βCTF degradation through autophagy. Here, we report the molecular mechanism by which PS1 modulates βCTF degradation. We show that PS1 phosphorylated at Ser367, but not nonphosphorylated PS1, interacts with Annexin A2, which, in turn, interacts with the lysosomal N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) Vamp8...
May 22, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28532681/resveratrol-protects-neuronal-like-cells-expressing-mutant-huntingtin-from-dopamine-toxicity-by-rescuing-atg4-mediated-autophagosome-formation
#18
Chiara Vidoni, Eleonora Secomandi, Andrea Castiglioni, Mariarosa A B Melone, Ciro Isidoro
Parkinsonian-like motor deficits in Huntington's Disease (HD) patients are associated with abnormal dopamine neurotransmission in the striatum. Dopamine metabolism leads to the formation of oxidized dopamine quinones that exacerbates mitochondrial dysfunction with production of reactive oxygen species (ROS) that eventually lead to neuronal cell death. We have previously shown that dopamine-induced oxidative stress triggers apoptotic cell death in dopaminergic neuroblastoma SH-SY5Y cells hyper-expressing the mutant polyQ Huntingtin (polyQ-Htt) protein...
May 19, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28531150/distinct-contributions-of-autophagy-receptors-in-measles-virus-replication
#19
Denitsa S Petkova, Pauline Verlhac, Aurore Rozières, Joël Baguet, Mathieu Claviere, Carole Kretz-Remy, Renaud Mahieux, Christophe Viret, Mathias Faure
Autophagy is a potent cell autonomous defense mechanism that engages the lysosomal pathway to fight intracellular pathogens. Several autophagy receptors can recognize invading pathogens in order to target them towards autophagy for their degradation after the fusion of pathogen-containing autophagosomes with lysosomes. However, numerous intracellular pathogens can avoid or exploit autophagy, among which is measles virus (MeV). This virus induces a complete autophagy flux, which is required to improve viral replication...
May 22, 2017: Viruses
https://www.readbyqxmd.com/read/28529589/tetrandrine-triggers-an-alternative-autophagy-in-du145-cells
#20
Wei Qiu, Ai-Li Zhang, Ye Tian
Tetrandrine (Tet), a potent lysosomal inhibitor, blocks autophagic flux and induces cancer cell death. Previously, the present authors identified the prostate cancer cell line DU145 to exhibit high sensitivity towards Tet in 11 cancer cell lines. In the present study, autophagy in Tet-treated DU145 cells was investigated. Similar to other cell lines, such as PC-3 and 786-O cells, Tet neutralized the acidity of lysosome and blocked autophagy in DU145 cells. However, Tet failed to induce microtubule-associated protein 1 light chain 3 (LC3) conversion in DU145 cells...
May 2017: Oncology Letters
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