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Autophagy

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https://www.readbyqxmd.com/read/28822991/aquatide-activation-of-sirt1-reduces-cellular-senescence-through-a-sirt1-foxo1-autophagy-axis
#1
Chae Jin Lim, Yong-Moon Lee, Seung Goo Kang, Hyung W Lim, Kyong-Oh Shin, Se Kyoo Jeong, Yang Hoon Huh, Suin Choi, Myungho Kor, Ho Seong Seo, Byeong Deog Park, Keedon Park, Jeong Keun Ahn, Yoshikazu Uchida, Kyungho Park
Ultraviolet (UV) irradiation is a relevant environment factor to induce cellular senescence and photoaging. Both autophagy- and silent information regulator T1 (SIRT1)-dependent pathways are critical cellular processes of not only maintaining normal cellular functions, but also protecting cellular senescence in skin exposed to UV irradiation. In the present studies, we investigated whether modulation of autophagy induction using a novel synthetic SIRT1 activator, heptasodium hexacarboxymethyl dipeptide-12 (named as Aquatide), suppresses the UVB irradiation-induced skin aging...
August 21, 2017: Biomolecules & Therapeutics
https://www.readbyqxmd.com/read/28822990/%C3%AE-%C3%AE-mangostins-induces-autophagy-and-shows-synergistic-effectwith-gemcitabine-in-pancreatic-cancer-cell-lines
#2
Myoungjae Kim, Young-Won Chin, Eun Joo Lee
Pancreatic cancer is one of the most lethal and aggressive cancers in the world. However, no effective treatment is currently available for pancreatic cancer. The objective of this study was to determine the anti-pancreatic cancer effect of α-mangostin (αM) and γ-mangostin (γM) extracted from the pericarp of Garcinia mangostana L.. Both αM and γM reduced the viability of pancreatic cancer cells MIA PaCa-2 and PANC-1 in a dose-dependent manner. These compounds induced apoptosis by increasing c-PARP and c-Caspase 3 levels...
August 21, 2017: Biomolecules & Therapeutics
https://www.readbyqxmd.com/read/28822801/microarray-gene-expression-study-in-fibroblast-and-lymphoblastoid-cell-lines-from-antipsychotic-na%C3%A3-ve-first-episode-schizophrenia-patients
#3
Patricia Gassó, Sergi Mas, Natalia Rodríguez, Daniel Boloc, Susana García-Cerro, Miquel Bernardo, Amalia Lafuente, Eduard Parellada
Schizophrenia (SZ) is a chronic psychiatric disorder whose onset of symptoms occurs in late adolescence and early adulthood. The etiology is complex and involves important gene-environment interactions. Microarray gene-expression studies on SZ have identified alterations in several biological processes. The heterogeneity in the results can be attributed to the use of different sample types and other important confounding factors including age, illness chronicity and antipsychotic exposure. The aim of the present microarray study was to analyze, for the first time to our knowledge, differences in gene expression profiles in 18 fibroblast (FCLs) and 14 lymphoblastoid cell lines (LCLs) from antipsychotic-naïve first-episode schizophrenia (FES) patients and healthy controls...
August 5, 2017: Journal of Psychiatric Research
https://www.readbyqxmd.com/read/28822762/rab11a-is-required-for-porcine-reproductive-and-respiratory-syndrome-virus-induced-autophagy-to-promote-viral-replication
#4
Kai Wang, Shuaifeng Li, Tesfaye Worku, Xingjie Hao, Liaohan Yang, Shujun Zhang
Porcine reproductive and respiratory syndrome virus (PRRSV) is the leading virus known to cause massive economic loss in pig industry worldwide. In our previous study, transcriptional profiling of PRRSV-infected lung tissue of Tongcheng and landrane pigs, which have highly pathogenic PRRSV (HP-PRRSV) susceptibility differences, showed differential expression of Rab11a. The small GTPase Rab11a regulates intracellular membrane trafficking events involved in autophagy. However, the involvement of convergence of endosomal Rab11a and autophagy pathways during PRRSV infection is still unclear...
August 16, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28822614/heterogeneity-in-a-large-pedigree-with-danon-disease-implications-for-pathogenesis-and-management
#5
Jonathan C P Roos, Matthew J Daniels, Elizabeth Morris, Hanna I Hyry, Timothy M Cox
BACKGROUND: Danon disease is an X-linked disturbance of autophagy manifesting with cognitive impairment and disordered heart and skeletal muscle. After a period of relative stability, patients deteriorate rapidly and may quickly become ineligible for elective heart transplantation - the only life-saving therapy. METHODS: We report a large pedigree with diverse manifestations of Danon disease in hemizygotes and female heterozygotes. RESULTS: Malignant cardiac arrhythmias requiring amiodarone treatment induced thyroid disease in two patients; intractable thyrotoxicosis, which enhances autophagy, caused the death of a 21year-old man...
June 21, 2017: Molecular Genetics and Metabolism
https://www.readbyqxmd.com/read/28821775/atf3-negatively-regulates-cellular-antiviral-signaling-and-autophagy-in-the-absence-of-type-i-interferons
#6
Vikas Sood, Kiran Bala Sharma, Vishal Gupta, Dhurjhoti Saha, Parashar Dhapola, Manish Sharma, Utsav Sen, Shigetaka Kitajima, Shantanu Chowdhury, Manjula Kalia, Sudhanshu Vrati
Stringent regulation of antiviral signaling and cellular autophagy is critical for the host response to virus infection. However, little is known how these cellular processes are regulated in the absence of type I interferon signaling. Here, we show that ATF3 is induced following Japanese encephalitis virus (JEV) infection, and regulates cellular antiviral and autophagy pathways in the absence of type I interferons in mouse neuronal cells. We have identified new targets of ATF3 and show that it binds to the promoter regions of Stat1, Irf9, Isg15 and Atg5 thereby inhibiting cellular antiviral signaling and autophagy...
August 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28821708/a-reversible-phospho-switch-mediated-by-ulk1-regulates-the-activity-of-autophagy-protease-atg4b
#7
N Pengo, A Agrotis, K Prak, J Jones, R Ketteler
Upon induction of autophagy, the ubiquitin-like protein LC3 is conjugated to phosphatidylethanolamine (PE) on the inner and outer membrane of autophagosomes to allow cargo selection and autophagosome formation. LC3 undergoes two processing steps, the proteolytic cleavage of pro-LC3 and the de-lipidation of LC3-PE from autophagosomes, both executed by the same cysteine protease ATG4. How ATG4 activity is regulated to co-ordinate these events is currently unknown. Here we find that ULK1, a protein kinase activated at the autophagosome formation site, phosphorylates human ATG4B on serine 316...
August 18, 2017: Nature Communications
https://www.readbyqxmd.com/read/28821398/urate-promotes-snca-%C3%AE-synuclein-clearance-via-regulating-mtor-dependent-macroautophagy
#8
Yu-Lan Sheng, Xing Chen, Xiao-Ou Hou, Xin-Yuan, Bao-Shi Yuan, Yu-Qing Yuan, Qi-Lin Zhang, Xian Cao, Chun-Feng Liu, Wei-Feng Luo, Li-Fang Hu
Serum urate levels are reported to be significantly lowered in patients with Parkinson's disease (PD) and inversely correlated to the risk and progression of PD. However, the mechanism by which urate affects PD is poorly understood. Here we showed that treatment with uric acid (UA) resulted in an autophagy activity enhancement in PC12 cells in dose- and time-dependent manners, as indicated by LC3-II increase and P62 decrease. Moreover, UA was still able to increase the LC3-II level and the number of LC3 puncta in the presence of Bafilomycin A1, a lysosomal inhibitor...
August 15, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28821011/the-photodynamic-action-of-pheophorbide-a-induces-cell-death-through-oxidative-stress-in-leishmania-amazonensis
#9
Nathielle Miranda, Hélito Volpato, Jean Henrique da Silva Rodrigues, Wilker Caetano, Tânia Ueda-Nakamura, Sueli de Oliveira Silva, Celso Vataru Nakamura
Leishmaniasis is a disease caused by hemoflagellate protozoa, affecting millions of people worldwide. The difficulties of treating patients with this parasitosis include the limited efficacy and many side effects of the currently available drugs. Therefore, the search for new compounds with leishmanicidal action is necessary. Photodynamic therapy has been studied in the medical field because of its selectivity, utilizing a combination of visible light, a photosensitizer compound, and singlet oxygen to reach the area of treatment...
August 11, 2017: Journal of Photochemistry and Photobiology. B, Biology
https://www.readbyqxmd.com/read/28820317/ulk1-ubiquitylation-is-regulated-by-phosphorylation-on-its-carboxy-terminus
#10
Francesca Nazio, Marianna Carinci, Francesco Cecconi
Autophagy is a highly conserved process that acts sequestering cytoplasmic components for their degradation by the lysosomes. It consists of several sequential steps that have to be finely regulated to ensure both its progression and termination. Post-translational modifications (PTMs) play an important role in regulating ATG proteins function in different stages of autophagy. Recently, we demonstrated that, during prolonged starvation, ULK1 protein is specifically ubiquitylated by NEDD4L, and that this regulation is important to protect cells against excessive autophagy...
August 18, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28820312/architecture-of-the-atg2b-wdr45-complex-and-an-aromatic-y-hf-motif-crucial-for-complex-formation
#11
Jing-Xiang Zheng, Yan Li, Yue-He Ding, Jun-Jie Liu, Mei-Jun Zhang, Meng-Qiu Dong, Hong-Wei Wang, Li Yu
PtdIns3P signaling is critical for dynamic membrane remodeling during autophagosome formation. Proteins in the Atg18/WIPI family are PtdIns3P-binding effectors which can form complexes with proteins in the Atg2 family, and both families are essential for macroautophagy/autophagy. However, little is known about the biophysical properties and biological functions of the Atg2-Atg18/WIPI complex as a whole. Here, we demonstrate that an ortholog of yeast Atg18, mammalian WDR45/WIPI4 has a stronger binding capacity for mammalian ATG2A or ATG2B than the other 3 WIPIs...
August 18, 2017: Autophagy
https://www.readbyqxmd.com/read/28820297/the-formation-of-autophagosomes-during-lysosomal-defect-a-new-source-of-cytotoxicity
#12
Robert W Button, Shouqing Luo
Macroautophagy/autophagy comprises autophagosome synthesis and lysosomal degradation. It is well known that lysosomal defects cause toxicity to cells. However, it has not been investigated previously if cytotoxicity is conferred by autophagosome formation during lysosomal defect. Recently, we found that the formation of autophagosomes in such conditions also causes cytotoxicity, in addition to lysosomal defect insults. We revealed that a partial reduction in autophagosome synthesis was beneficial for cell survival in cells bearing the autophagosome formation-based toxicity...
August 18, 2017: Autophagy
https://www.readbyqxmd.com/read/28820290/local-histone-acetylation-by-acss2-promotes-gene-transcription-for-lysosomal-biogenesis-and-autophagy
#13
Xinjian Li, Xu Qian, Zhimin Lu
Overcoming metabolic stress is a critical step in tumorigenesis. Acetyl coenzyme A (acetyl-CoA) converted from glucose or acetate is a substrate used for histone acetylation to regulate gene expression. However, how acetyl-CoA is produced under nutritional stress conditions is unclear. Herein we report that nutritional stress induces nuclear translocation of ACSS2 (acyl-CoA synthetase short-chain family member 2). This translocation is mediated by AMP-activated protein kinase (AMPK)-dependent ACSS2 Ser659 phosphorylation and subsequent exposure of the nuclear localization signal of ACSS2 to KPNA1/importin α5 for binding...
August 18, 2017: Autophagy
https://www.readbyqxmd.com/read/28820289/recent-advances-in-quantitative-and-chemical-proteomics-for-autophagy-studies
#14
Yin-Kwan Wong, Jianbin Zhang, Zi-Chun Hua, Qingsong Lin, Han-Ming Shen, Jigang Wang
Macroautophagy/autophagy is an evolutionarily well-conserved cellular degradative process with important biological functions that is closely implicated in health and disease. In recent years, quantitative mass spectrometry-based proteomics and chemical proteomics have emerged as important tools for the study of autophagy, through large-scale unbiased analysis of the proteome or through highly specific and accurate analysis of individual proteins of interest. At present, a variety of approaches have been successfully applied, including (i) expression and interaction proteomics for the study of protein post-translational modifications, (ii) investigating spatio-temporal dynamics of protein synthesis and degradation, and (iii) direct determination of protein activity and profiling molecular targets in the autophagic process...
August 18, 2017: Autophagy
https://www.readbyqxmd.com/read/28820286/autophagy-monitoring-and-autophagy-deficient-mice
#15
Akiko Kuma, Masaaki Komatsu, Noboru Mizushima
Discovery of yeast autophagy-related (ATG) genes and subsequent identification of their homologs in other organisms have enabled researchers to investigate physiological functions of macroautophagy/autophagy using genetic techniques. Specific identification of autophagy-related structures is important to evaluate autophagic activity, and specific ablation of autophagy-related genes is a critical means to determine the requirements of autophagy. Here, we review currently available mouse models, particularly focusing on autophagy (and mitophagy) indicator models and systemic autophagy-related gene-knockout mouse models...
August 18, 2017: Autophagy
https://www.readbyqxmd.com/read/28820283/n-3-pufas-induce-inflammatory-tolerance-by-formation-of-keap1-containing-sqstm1-p62-bodies-and-activation-of-nfe2l2
#16
Jennifer Mildenberger, Ida Johansson, Ismail Sergin, Eli Kjøbli, Jan Kristian Damås, Babak Razani, Trude Helen Flo, Geir Bjørkøy
Inflammation is crucial in the defense against infections but must be tightly controlled to limit detrimental hyperactivation. Our diet influences inflammatory processes and omega-3 polyunsaturated fatty acids (n-3 PUFAs) have known anti-inflammatory effects. The balance of pro- and anti-inflammatory processes is coordinated by macrophages and macroautophagy/autophagy has recently emerged as a cellular process that dampens inflammation. Here we report that the n-3 PUFA docosahexaenoic acid (DHA) transiently induces cytosolic speckles of the autophagic receptor SQSTM1/p62 (sequestosome 1) (described as SQSTM1/p62-bodies) in macrophages...
August 18, 2017: Autophagy
https://www.readbyqxmd.com/read/28820282/mir505-3p-regulates-axonal-development-via-inhibiting-the-autophagy-pathway-by-targeting-atg12
#17
Kan Yang, Bin Yu, Cheng Cheng, Tianlin Cheng, Bo Yuan, Kai Li, Junhua Xiao, Zilong Qiu, Yuxun Zhou
In addition to the canonical role in protein homeostasis, autophagy has recently been found to be involved in axonal dystrophy and neurodegeneration. Whether autophagy may also be involved in neural development remains largely unclear. Here we report that Mir505-3p is a crucial regulator for axonal elongation and branching in vitro and in vivo, through modulating autophagy in neurons. We identify that the key target gene of Mir505-3p in neurons is Atg12, encoding ATG12 (autophagy related 12) which is an essential component of the autophagy machinery during the initiation and expansion steps of autophagosome formation...
August 18, 2017: Autophagy
https://www.readbyqxmd.com/read/28819333/expression-of-autophagy-related-proteins-in-h%C3%A3-rthle-cell-neoplasm-is-different-from-that-in-follicular-neoplasm
#18
Yoon Jin Cha, Hye Min Kim, Ja Seung Koo
PURPOSE: We aimed to evaluate expression of autophagy-related proteins in Hürthle cell neoplasm (HCN) and follicular neoplasm (FN) and assess the clinical implications. METHODS: 265 FNs (112 follicular carcinomas and 153 follicular adenomas) and 108 HCNs (27 Hürthle cell carcinomas and 81 Hürthle cell adenomas) were made into a tissue microarray. Immunohistochemical staining and Western blot for autophagy-related proteins (beclin-1, light chain (LC) 3A, LC3B, p62, and BNIP3) were performed, and the results were statistically analyzed...
2017: Disease Markers
https://www.readbyqxmd.com/read/28819266/amalaki-rasayana-a-traditional-indian-drug-enhances-cardiac-mitochondrial-and-contractile-functions-and-improves-cardiac-function-in-rats-with-hypertrophy
#19
Vikas Kumar, Kumar A Aneesh, K Kshemada, Kumar G S Ajith, Raj S S Binil, Neha Deora, G Sanjay, A Jaleel, T S Muraleedharan, E M Anandan, R S Mony, M S Valiathan, Kumar T R Santhosh, C C Kartha
We evaluated the cardioprotective effect of Amalaki Rasayana (AR), a rejuvenating Ayurvedic drug prepared from Phyllanthus emblica fruits in the reversal of remodeling changes in pressure overload left ventricular cardiac hypertrophy (LVH) and age-associated cardiac dysfunction in male Wistar rats. Six groups (aging groups) of 3 months old animals were given either AR or ghee and honey (GH) orally; seventh group was untreated. Ascending aorta was constricted using titanium clips in 3 months old rats (N = 24; AC groups) and after 6 months, AR or GH was given for further 12 months to two groups; one group was untreated...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28819237/disruption-of-the-plant-specific-cfs1-gene-impairs-autophagosome-turnover-and-triggers-eds1-dependent-cell-death
#20
Arpaporn Sutipatanasomboon, Stefanie Herberth, Ellen G Alwood, Heidrun Häweker, Britta Müller, Mojgan Shahriari, Anke Y Zienert, Birger Marin, Silke Robatzek, Gerrit J K Praefcke, Kathryn R Ayscough, Martin Hülskamp, Swen Schellmann
Cell death, autophagy and endosomal sorting contribute to many physiological, developmental and immunological processes in plants. They are mechanistically interconnected and interdependent, but the molecular basis of their mutual regulation has only begun to emerge in plants. Here, we describe the identification and molecular characterization of CELL DEATH RELATED ENDOSOMAL FYVE/SYLF PROTEIN 1 (CFS1). The CFS1 protein interacts with the ENDOSOMAL SORTING COMPLEX REQUIRED FOR TRANSPORT I (ESCRT-I) component ELCH (ELC) and is localized at ESCRT-I-positive late endosomes likely through its PI3P and actin binding SH3YL1 Ysc84/Lsb4p Lsb3p plant FYVE (SYLF) domain...
August 17, 2017: Scientific Reports
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