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https://www.readbyqxmd.com/read/29036198/the-homeodomain-interacting-protein-kinase-hpk-1-preserves-protein-homeostasis-and-longevity-through-master-regulatory-control-of-the-hsf-1-chaperone-network-and-torc1-restricted-autophagy-in-caenorhabditis-elegans
#1
Ritika Das, Justine A Melo, Manjunatha Thondamal, Elizabeth A Morton, Adam B Cornwell, Beresford Crick, Joung Heon Kim, Elliot W Swartz, Todd Lamitina, Peter M Douglas, Andrew V Samuelson
An extensive proteostatic network comprised of molecular chaperones and protein clearance mechanisms functions collectively to preserve the integrity and resiliency of the proteome. The efficacy of this network deteriorates during aging, coinciding with many clinical manifestations, including protein aggregation diseases of the nervous system. A decline in proteostasis can be delayed through the activation of cytoprotective transcriptional responses, which are sensitive to environmental stress and internal metabolic and physiological cues...
October 16, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/29035377/nme4-nucleoside-diphosphate-kinase-d-in-cardiolipin-signaling-and-mitophagy
#2
Uwe Schlattner, Malgorzata Tokarska-Schlattner, Richard M Epand, Mathieu Boissan, Marie-Lise Lacombe, Valerian E Kagan
Mitophagy is an emerging paradigm for mitochondrial quality control and cell homeostasis. Dysregulation of mitophagy can lead to human pathologies such as neurodegenerative disorders and contributes to the aging process. Complex protein signaling cascades have been described that regulate mitophagy. We have identified a novel lipid signaling pathway that involves the phospholipid cardiolipin (CL). CL is synthesized and normally confined at the inner mitochondrial membrane. However, upon a mitophagic trigger, ie, collapse of the inner membrane potential, CL is rapidly externalized to the mitochondrial surface with the assistance of the hexameric nucleoside diphosphate kinase D (NME4, NDPK-D, or NM23-H4)...
October 16, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/29034767/in-search-of-a-converging-cellular-mechanism-in-nanotoxicology-and-nanomedicine-in-the-treatment-of-cancer
#3
Mary Gulumian, Charlene Andraos
Multiple applications of nanomaterials have raised concern with regard to their toxicity. With increasing research into nanomaterial safety, mechanisms involved in the toxic effects of nanomaterials have begun to emerge. The importance of nanomaterial-induced lysosomal membrane permeabilization through overloading or direct damage of the lysosomal compartment, resulting in the blockade of autophagosome-lysosome fusion and autophagy dysfunction, as well as inflammasome activation were cited as emerging mechanisms of nanomaterial toxicity...
January 1, 2017: Toxicologic Pathology
https://www.readbyqxmd.com/read/29031088/probing-the-correlation-of-neuronal-loss-neurofibrillary-tangles-and-cell-death-markers-across-the-alzheimer-s-disease-braak-stages-a-quantitative-study-in-humans
#4
Panos Theofilas, Alexander J Ehrenberg, Austin Nguy, Julia M Thackrey, Sara Dunlop, Maria B Mejia, Ana T Alho, Renata Elaine Paraizo Leite, Roberta Diehl Rodriguez, Claudia K Suemoto, Camila F Nascimento, Marcus Chin, Daniel Medina-Cleghorn, Ana Maria Cuervo, Michelle Arkin, William W Seeley, Bruce L Miller, Ricardo Nitrini, Carlos Augusto Pasqualucci, Wilson Jacob Filho, Udo Rueb, John Neuhaus, Helmut Heinsen, Lea T Grinberg
Clarifying the mechanisms connecting neurofibrillary tangle (NFT) neurotoxicity to neuronal dysfunction in humans is likely to be pivotal for developing effective treatments for Alzheimer's disease (AD). To model the temporal progression of AD in humans, we used a collection of brains with controls and individuals from each Braak stage to quantitatively investigate the correlation between intraneuronal caspase activation or macroautophagy markers, NFT burden, and neuronal loss, in the dorsal raphe nucleus and locus coeruleus, the earliest vulnerable areas to NFT accumulation...
September 20, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/29030482/membrane-scission-driven-by-the-proppin-atg18
#5
Navin Gopaldass, Bruno Fauvet, Hilal Lashuel, Aurélien Roux, Andreas Mayer
Sorting, transport, and autophagic degradation of proteins in endosomes and lysosomes, as well as the division of these organelles, depend on scission of membrane-bound tubulo-vesicular carriers. How scission occurs is poorly understood, but family proteins bind these membranes. Here, we show that the yeast PROPPIN Atg18 carries membrane scission activity. Purified Atg18 drives tubulation and scission of giant unilamellar vesicles. Upon membrane contact, Atg18 folds its unstructured CD loop into an amphipathic α-helix that inserts into the bilayer...
October 13, 2017: EMBO Journal
https://www.readbyqxmd.com/read/29029506/bitter-melon-extract-inhibits-breast-cancer-growth-in-preclinical-model-by-inducing-autophagic-cell-death
#6
Naoshad Muhammad, Robert Steele, T Scott Isbell, Nancy Philips, Ratna B Ray
Breast cancer is a major public health problem worldwide in women and current therapeutic strategies are not adequately effective for this deadly disease. We have previously shown the anti-proliferative activity of bitter melon extract (BME) in breast cancer cells. In this study, we observed that BME treatment induces autophagosome-bound Long chain 3 (LC3)-B and accumulates protein p62/SQSTM1 (p62) in breast cancer cells. Additionally, we observed that BME treatment in breast cancer cells increases phospho-AMPK expression and inhibits the mTOR/Akt signaling pathway...
September 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29028815/striatal-astrocytes-engulf-dopaminergic-debris-in-parkinson-s-disease-a-study-in-an-animal-model
#7
Ingrid Morales, Alberto Sanchez, Clara Rodriguez-Sabate, Manuel Rodriguez
The role of astrocytes in Parkinson's disease is still not well understood. This work studied the astrocytic response to the dopaminergic denervation. Rats were injected in the lateral ventricles with 6-hydroxydopamine (25μg), inducing a dopaminergic denervation of the striatum not accompanied by non-selective tissue damage. The dopaminergic debris were found within spheroids (free-spheroids) which retained some proteins of dopaminergic neurons (e.g., tyrosine hydroxylase, the dopamine transporter protein, and APP) but not others (e...
2017: PloS One
https://www.readbyqxmd.com/read/29027991/n6-isopentenyladenosine-dual-targeting-of-ampk-and-rab7-prenylation-inhibits-melanoma-growth-through-the-impairment-of-autophagic-flux
#8
Roberta Ranieri, Elena Ciaglia, Giuseppina Amodio, Paola Picardi, Maria Chiara Proto, Patrizia Gazzerro, Chiara Laezza, Paolo Remondelli, Maurizio Bifulco, Simona Pisanti
Targeting the autophagic process is considered a promising therapeutic strategy in cancer since a great number of tumors, including melanoma, show high basal levels of protective autophagy that contributes to tumor progression and chemoresistance. Here, exploiting both in vitro and in vivo approaches, we identified N6-isopentenyladenosine (iPA), an end product of the mevalonate pathway, as a novel autophagy inhibitor with an interesting anti-melanoma activity. iPA, after being phosphorylated by adenosine kinase into 5'-iPA-monophosphate, induces autophagosome accumulation through AMPK activation, measured by increased fluorescent GFP-LC3 puncta and enhanced conversion into the lipidated autophagosome-associated LC3-II...
October 13, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29025974/lipid-based-dna-sirna-transfection-agents-disrupt-neuronal-bioenergetics-and-mitophagy
#9
Eleonora Napoli, Siming Liu, Ilaria Marsilio, Konstantinos Zarbalis, Cecilia Giulivi
A multitude of natural and artificial compounds have been recognized to modulate autophagy, providing direct or, through associated pathways, indirect entry points to activation and inhibition. While these pharmacological tools are extremely useful in the study of autophagy, their abundance also suggests the potential presence of unidentified autophagic modulators that may interfere with experimental designs if applied unknowingly. Here, we report unanticipated effects on autophagy and bioenergetics in neuronal progenitor cells (NPC) incubated with widely used lipid-based-transfection reagent lipofectamine (LF), which induced mitochondria depolarization followed by disruption of electron transport...
October 12, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/29024815/identification-of-a-novel-autophagic-inhibitor-cepharanthine-to-enhance-the-anti-cancer-property-of-dacomitinib-in-non-small-cell-lung-cancer
#10
Zheng-Hai Tang, Wen-Xiang Cao, Xia Guo, Xiao-Yang Dai, Jia-Hong Lu, Xiuping Chen, Hong Zhu, Jin-Jian Lu
Inhibition of autophagy is a promising strategy for non-small cell lung cancer (NSCLC) treatment, which is in the clinical trials. However, only chloroquine is used in clinic as an autophagic inhibitor and the inhibitory effect of chloroquine on autophagy is finite. Therefore, the development of an alternative autophagic inhibitor for NSCLC therapy becomes necessary. In the present study, cepharanthine (CEP), an alkaloid extracted from Stephania cepharantha Hayata, was identified as a novel autophagic inhibitor in NSCLC cells...
October 9, 2017: Cancer Letters
https://www.readbyqxmd.com/read/29023824/cholangiocyte-autophagy-contributes-to-hepatic-cystogenesis-in-polycystic-liver-disease-and-represents-a-potential-therapeutic-target
#11
Anatoliy I Masyuk, Tatyana V Masyuk, Maria J Lorenzo Pisarello, Jingyi Francess Ding, Lorena Loarca, Bing Q Huang, Nicholas F LaRusso
Polycystic liver disease (PLD) is a group of genetic disorders with limited treatment and significant morbidity. Hepatic cysts arise from cholangiocytes exhibiting a hyperproliferative phenotype. Considering that hyperproliferation of many cell types is associated with alterations in autophagy, we hypothesized that autophagy is altered in PLD cholangiocytes, contributes to hepatic cystogenesis, and might represent a potential therapeutic target. We employed Functional Pathway Cluster Analysis (FPCA) and NextGen Sequencing (NGS), transmission electron microscopy, immunofluorescence confocal microscopy, and western blotting to assess autophagy in human and rodent PLD cholangiocytes...
October 10, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29022917/trehalose-protects-against-cadmium-induced-cytotoxicity-in-primary-rat-proximal-tubular-cells-via-inhibiting-apoptosis-and-restoring-autophagic-flux
#12
Xin-Yu Wang, Heng Yang, Min-Ge Wang, Du-Bao Yang, Zhen-Yong Wang, Lin Wang
Autophagy has an important renoprotective function and we recently found that autophagy inhibition is involved in cadmium (Cd)-induced nephrotoxicity. Here, we aimed to investigate the protective effect of trehalose (Tre), a novel autophagy activator, against Cd-induced cytotoxicity in primary rat proximal tubular (rPT) cells. First, data showed that Tre treatment significantly decreased Cd-induced apoptotic cell death of rPT cells via inhibiting caspase-dependent apoptotic pathway, evidenced by morphological analysis, flow cytometric and immunoblot assays...
October 12, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/29022891/escin-induces-caspase-dependent-apoptosis-and-autophagy-through-the-ros-p38-mapk-signalling-pathway-in-human-osteosarcoma-cells-in-vitro-and-in-vivo
#13
Jian Zhu, Wei Yu, Bing Liu, Yitian Wang, Jianlin Shao, Junjie Wang, Kaishun Xia, Chengzhen Liang, Weijing Fang, Chenhe Zhou, Huimin Tao
Osteosarcoma is one of the most malignant neoplasms in adolescents, and it generally develops multidrug resistance. Escin, a natural mixture of triterpene saponins isolated from Aesculus hippocastanum (horse chestnut), has demonstrated potent anti-tumour potential in vitro and in vivo. In the present study, we found that escin inhibited osteosarcoma proliferation in a dose- and time-dependent manner. Additionally, escin-induced apoptosis was evidenced by the increased expression of caspase-related proteins and the formation of apoptotic bodies...
October 12, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/29021346/the-hect-e3-ubiquitin-ligase-nedd4-interacts-with-and-ubiquitinates-sqstm1-for-inclusion-body-autophagy
#14
Qiong Lin, Qian Dai, Hongxia Meng, Aiqin Sun, Jing Wei, Ke Peng, Chandra Childress, Miao Chen, Genbao Shao, Wannian Yang
Our previous studies have shown that the HECT E3 ubiquitin ligase NEDD4 interacts with LC3 and is required for starvation and rapamycin-induced activation of autophagy. Here we report that NEDD4 directly binds to SQSTM1 via its HECT domain and poly-ubiquitinates SQSTM1. This ubiquitination is through K63 conjugation and not involved in proteasomal degradation. Mutational analysis indicates that NEDD4 interacts with and ubiquitinates the PB1 domain of SQSTM1. Depletion of NEDD4 or overexpression of the ligase defective mutant of NEDD4 induced accumulation of aberrant enlarged SQSTM1-positive inclusion bodies that are co-localized with the endoplasmic reticulum (ER) marker CANX, suggesting that the ubiquitination functions in the SQSTM1-mediated biogenic process of inclusion body autophagosomes...
October 11, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/29019932/asic1a-promotes-acid-induced-autophagy-in-rat-articular-chondrocytes-through-the-ampk-foxo3a-pathway
#15
Beibei Dai, Fei Zhu, Yong Chen, Renpeng Zhou, Zhisen Wang, Yaya Xie, Xiaoshan Wu, Shengqin Zu, Ge Li, Jinfang Ge, Feihu Chen
Acid-sensing ion channel 1a (ASIC1a) is a member of the extracellular H⁺-activated cation channels family. Our previous studies suggested that ASIC1a contributed to acid-induced rat articular chondrocytes autophagy. However, its potential mechanisms remain unclear. The present study demonstrated the effect of ASIC1a on rat articular chondrocytes autophagy and explored the underlying molecular mechanisms. The results demonstrated that ASIC1a contributed to acid-induced autophagy in rat articular chondrocytes, and which was associated with an increase in (Ca(2+))i, as indicated that acid-induced increases in mRNA and protein expression of LC3B-II and other autophagy-related markers were inhibited by ASIC1a-specific blocker, PcTx1 and calcium chelating agent, BAPTA-AM...
October 11, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29018434/commentary-toxoplasma-depends-on-lysosomal-consumption-of-autophagosomes-for-persistent-infection
#16
COMMENT
Giovanni Di Guardo
No abstract text is available yet for this article.
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29018327/maternal-cigarette-smoke-exposure-worsens-neurological-outcomes-in-adolescent-offspring-with-hypoxic-ischemic-injury
#17
Yik L Chan, Sonia Saad, Rita Machaalani, Brian G Oliver, Bryce Vissel, Carol Pollock, Nicole M Jones, Hui Chen
Hypoxic-ischemic (HI) encephalopathy occurs in approximately 6 per 1000 term newborns leading to devastating neurological consequences, such as cerebral palsy and seizures. Maternal smoking is one of the prominent risk factors contributing to HI injury. Mitochondrial integrity plays a critical role in neural injury and repair during HI. We previously showed that maternal cigarette smoke exposure (SE) can reduce brain mitochondrial fission and autophagosome markers in male offspring. This was accompanied by increased brain cell apoptosis (active caspase-3) and DNA fragmentation (TUNEL staining)...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28994404/identification-biochemical-characterization-and-crystallization-of-the-central-region-of-human-atg16l1
#18
Archna Archna, Andrea Scrima
ATG16L1 plays a major role in autophagy. It acts as a molecular scaffold which mediates protein-protein interactions essential for autophagosome formation. The ATG12~ATG5-ATG16L1 complex is one of the key complexes involved in autophagosome formation. Human ATG16L1 comprises 607 amino acids with three functional domains named ATG5BD, CCD and WD40, where the C-terminal WD40 domain represents approximately 50% of the full-length protein. Previously, structures of the C-terminal WD40 domain of human ATG16L1 as well as of human ATG12~ATG5 in complex with the ATG5BD of ATG16L1 have been reported...
October 1, 2017: Acta Crystallographica. Section F, Structural Biology Communications
https://www.readbyqxmd.com/read/28994193/interplay-between-fgfr2b-induced-autophagy-and-phagocytosis-role-of-plc%C3%AE-mediated-signalling
#19
Monica Nanni, Danilo Ranieri, Salvatore Raffa, Maria Rosaria Torrisi, Francesca Belleudi
Signalling of the epithelial splicing variant of the fibroblast growth factor receptor 2 (FGFR2b) induces both autophagy and phagocytosis in human keratinocytes. Here, we investigated, in the cell model of HaCaT keratinocytes, whether the two processes might be related and the possible involvement of PLCγ signalling. Using fluorescence and electron microscopy, we demonstrated that the FGFR2b-induced phagocytosis and autophagy involve converging autophagosomal and phagosomal compartments. Moreover, the forced expression of FGFR2b signalling mutants and the use of specific inhibitors of FGFR2b substrates showed that the receptor-triggered autophagy requires PLCγ signalling, which in turn activates JNK1 via PKCδ...
October 10, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28993455/ehrlichia-activation-of-wnt-pi3k-mtor-signaling-inhibits-autolysosome-generation-and-autophagic-destruction-by-the-mononuclear-phagocyte
#20
Taslima T Lina, Tian Luo, Thangam-Sudha Velayutham, Seema Das, Jere W McBride
In multicellular organisms, autophagy is induced as an innate defense mechanism. Notably, the obligate intracellular bacterium, Ehrlichia chaffeensis, resides in early endosome-like vacuoles and circumvents lysosomal fusion through an unknown mechanism, thereby avoiding destruction in the autophagolysosome. In this study, we reveal that Wnt signaling plays a crucial role in inhibition of lysosomal fusion and autolysosomal destruction of ehrlichiae. During early infection, autophagosomes fuse with ehrlichial vacuoles to form an amphisome indicated by presence of autophagy markers such as LC3, Beclin-1 and p62...
October 9, 2017: Infection and Immunity
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