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endoplasmic reticulum and autophagy

Maioli E, Daveri E, Maellaro E, Ietta F, Cresti L, Valacchi G
In the past few years, we focused the interest on rottlerin, an old/new natural substance that, over the time, has revealed a number of cellular and molecular targets, all potentially implicated in the fight against cancer. Past and recent literature well demonstrated that rottlerin is an inhibitor of enzymes, transcription factors and signaling molecules that control cancer cell life and death. Although the rottlerin anticancer activity has been mainly ascribed to apoptosis and/or autophagy induction, recent findings unveiled the existence of additional mechanisms of toxicity...
March 12, 2018: Archives of Biochemistry and Biophysics
Jianrong Li, Qilin Yu, Bing Zhang, Chenpeng Xiao, Tianyu Ma, Xiao Yi, Chao Liang, Mingchun Li
Cellular stresses could activate several response processes, such as the unfolded protein response (UPR), autophagy and oxidative stress response to restore cellular homeostasis or render cell death. Herein, we identified the Candida albicans stress-associated endoplasmic reticulum protein 1 (SERP1), also known as Ysy6, which was involved in endoplasmic reticulum (ER) stress response. We found that deletion of both SERP1/YSY6 and ATG8 led to hypersensitivity to tunicamycin (TN), and resulted in severe mitochondrial dysfunction under this stress...
March 6, 2018: International Journal of Medical Microbiology: IJMM
Joy Ogbechi, Belinda S Hall, Thomas Sbarrato, Jack Taunton, Anne E Willis, Ronald C Wek, Rachel E Simmonds
Mycolactone is the exotoxin virulence factor of Mycobacterium ulcerans that causes the neglected tropical disease Buruli ulcer. We recently showed it to be a broad spectrum inhibitor of Sec61-dependent co-translational translocation of proteins into the endoplasmic reticulum (ER). An outstanding question is the molecular pathway linking this to its known cytotoxicity. We have now used translational profiling to better understand the reprogramming that occurs in cells exposed to mycolactone. Gene ontology identified enrichment in genes involved in cellular response to stress, and apoptosis signalling among those showing enhanced translation...
March 14, 2018: Cell Death & Disease
Yumao Jiang, Yue Jiao, Yang Liu, Meiyu Zhang, Zhiguo Wang, Yujuan Li, Tao Li, Xiaoliang Zhao, Danqiao Wang
As shown in our previous study, sinomenine hydrochloride (SH), the major bioactive alkaloid isolated from Sinomenium acutum Rehd. et Wils. (Fam. Menispermaceae ), initiates the autophagy-mediated death of human glioblastoma cells by generating reactive oxygen species and activating the autophagy-lysosome pathway. However, its effects on the migration and invasion of human glioblastoma cells have not yet been elucidated. Therefore, human glioblastoma U87 and SF767 cells were treated with SH (0.125 and 0.25 mM) for 24 h, and cell migration and invasion were assessed using scratch wound healing, migration and invasion assays...
March 14, 2018: International Journal of Molecular Sciences
Wen-Jun Yan, Ruo-Bin Liu, Ling-Kai Wang, Ya-Bing Ma, Shao-Li Ding, Fei Deng, Zhong-Yuan Hu, Da-Bin Wang
Endoplasmic reticulum (ER) stress occurring in stringent conditions is critically involved in neuronal survival and death. Resveratrol is a non-flavonoid polyphenol that has neuroprotective effects against many neurological disorders. Here, we investigated the potential protective effects of resveratrol in an in vitro ER stress model mimicked by tunicamycin (TM) treatment in neuronal HT22 cells. We found that TM dose-dependently decreased cell viability and increased apoptosis, which were both significantly attenuated by resveratrol treatment...
2018: Frontiers in Neuroscience
Antonello Storniolo, Vincenzo Alfano, Sabino Carbotta, Elisabetta Ferretti, Livia Di Renzo
Sensors of endoplasmic reticulum (ER) stress function in a co-ordinated manner. In the present study we investigated the relationship between IRE1α and PERK pathways and survival of ER stressed U937 cells and BC3 cells. To this end, we investigated the effects of a subcytotoxic concentration of Tunicamycin in IRE1α-proficient and in IRE1α-deficient cells, by pharmacological inhibition with 4μ8 C or down-regulation by specific siRNA. We show that either type of IRE1α deficiency affects eIF2α expression and causes cell death increase...
December 2018: Cell Death Discovery
Hongyan Wu, Qing Chang
Valvular diseases are common health problems that are strongly related to high morbidity and mortality; aortic valve allograft transplantation may be a promising way to improve survival and relieve symptoms. However, ideal tissue viability has not been observed with common valve cryopreservation methods, which could lead to apoptosis and necrosis in cryopreserved tissue. It has been observed that trehalose plays a positive role by acting to maintain cell structures and protect cells from stress responses. In this study, we studied the effects of trehalose in protecting rat valve tissue from the cooling process...
2018: PloS One
Ji Tu, Wentian Li, Shuai Li, Wei Liu, Yukun Zhang, Xinghuo Wu, Rongjin Luo, Wenbin Hua, Kun Wang, Yu Song, Liang Kang, Wen Yang, Shuhua Yang, Cao Yang
BACKGROUND/AIMS: Intervertebral disc degeneration (IDD) is a pathological process that is the primary cause of low back pain and is potentially mediated by compromised stress defense. Sestrins (Sesn) promote cell survival under stress conditions and regulate AMP-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR) signaling. Here, we investigated the expression of Sesn in normal and degraded nucleus pulposus (NP) cells and its potential roles during IDD pathogenesis...
March 2, 2018: Cellular Physiology and Biochemistry
Miriam Buttacavoli, Nadia Ninfa Albanese, Gianluca Di Cara, Rosa Alduina, Claudia Faleri, Michele Gallo, Giuseppe Pizzolanti, Giuseppe Gallo, Salvatore Feo, Franco Baldi, Patrizia Cancemi
Silver nanoparticles (AgNPs), embedded into a specific polysaccharide (EPS), were biogenerated by Klebsiella oxytoca DSM 29614 under aerobic (AgNPs-EPSaer ) and anaerobic conditions (AgNPs-EPSanaer ). Both AgNPs-EPS matrices were tested by MTT assay for cytotoxic activity against human breast (SKBR3 and 8701-BC) and colon (HT-29, HCT 116 and Caco-2) cancer cell lines, revealing AgNPs-EPSaer as the most active, in terms of IC50, with a more pronounced efficacy against breast cancer cell lines. Therefore, colony forming capability, morphological changes, generation of reactive oxygen species (ROS), induction of apoptosis and autophagy, inhibition of migratory and invasive capabilities and proteomic changes were investigated using SKBR3 breast cancer cells with the aim to elucidate AgNPs-EPSaer mode of action...
February 9, 2018: Oncotarget
Leonardo Iula, Irene A Keitelman, Florencia Sabbione, Federico Fuentes, Mauricio Guzman, Jeremías Gastón Galletti, Pehuén Pereyra Gerber, Matías Ostrowski, Jorge R Geffner, Carolina C Jancic, Analía S Trevani
Interleukin-1β (IL-1β), a major pro-inflammatory cytokine, is a leaderless cytosolic protein whose secretion does not follow the classical endoplasmic reticulum-to-Golgi pathway, and for which a canonical mechanism of secretion remains to be established. Neutrophils are essential players against bacterial and fungi infections. These cells are rapidly and massively recruited from the circulation into infected tissues and, beyond of displaying an impressive arsenal of toxic weapons effective to kill pathogens, are also an important source of IL-1β in infectious conditions...
2018: Frontiers in Immunology
Patricia Gómez-Suaga, José M Bravo-San Pedro, Rosa A González-Polo, José M Fuentes, Mireia Niso-Santano
Mitochondria form close physical contacts with a specialized domain of the endoplasmic reticulum (ER), known as the mitochondria-associated membrane (MAM). This association constitutes a key signaling hub to regulate several fundamental cellular processes. Alterations in ER-mitochondria signaling have pleiotropic effects on a variety of intracellular events resulting in mitochondrial damage, Ca2+ dyshomeostasis, ER stress and defects in lipid metabolism and autophagy. Intriguingly, many of these cellular processes are perturbed in neurodegenerative diseases...
March 1, 2018: Cell Death & Disease
Priyanka Dutta, Leila Dargahi, Kara E O'Connell, Ashini Bolia, Banu Ozkan, Andreas W Sailer, Kumlesh K Dev
Parkin associated endothelin like receptor (PAELR) is G-protein coupled and ubiquitinated by parkin, promoting its degradation. In autosomal recessive Parkinson's disease, mutations in parkin lead to PAELR aggregation in the endoplasmic reticulum (ER), ER stress, neurotoxicity and cell death. We have identified previously that the protein kinase C interacting protein (PICK1) interacts with and regulates the expression and cell toxicity of PAELR. Here, we experimentally identify and provide in-silico modelling of a novel interaction between PAELR and GABARAPL2 (γ-aminobutyrate type A receptor associated protein like 2), which is an autophagosome-specific Ub-like protein implicated in vesicle trafficking and autophagy...
February 26, 2018: Neuroscience Letters
Yan G Zhao, Hong Zhang
The ER forms contacts with other endomembrane systems to exchange materials (e.g., calcium and lipids) and also to modulate dynamic organelle processes, including fission, cargo sorting and movement. During autophagosome formation, dynamic contacts between the ER and the phagophore membrane are crucial for phagophore expansion and closure. Little is known about the mechanisms underlying the formation and disassembly of the ER contacts. We found that the ER-localized autophagy protein EPG-3/VMP1 plays an essential role in controlling ER-phagophore dissociation and also the disassembly of ER contacts with LDs, mitochondria and endolysosomes...
March 1, 2018: Autophagy
Justyna Janikiewicz, Jędrzej Szymański, Dominika Malinska, Paulina Patalas-Krawczyk, Bernadeta Michalska, Jerzy Duszyński, Carlotta Giorgi, Massimo Bonora, Agnieszka Dobrzyn, Mariusz R Wieckowski
Sites of close contact between mitochondria and the endoplasmic reticulum (ER) are known as mitochondria-associated membranes (MAM) or mitochondria-ER contacts (MERCs), and play an important role in both cell physiology and pathology. A growing body of evidence indicates that changes observed in the molecular composition of MAM and in the number of MERCs predisposes MAM to be considered a dynamic structure. Its involvement in processes such as lipid biosynthesis and trafficking, calcium homeostasis, reactive oxygen species production, and autophagy has been experimentally confirmed...
February 28, 2018: Cell Death & Disease
Nathalie Bernard-Marissal, Roman Chrast, Bernard L Schneider
Recent progress in the understanding of neurodegenerative diseases revealed that multiple molecular mechanisms contribute to pathological changes in neurons. A large fraction of these alterations can be linked to dysfunction in the endoplasmic reticulum (ER) and mitochondria, affecting metabolism and secretion of lipids and proteins, calcium homeostasis, and energy production. Remarkably, these organelles are interacting with each other at specialized domains on the ER called mitochondria-associated membranes (MAMs)...
February 28, 2018: Cell Death & Disease
Yeong-Min Yoo, Yung Chul Park
Streptozotocin (STZ), a glucose analog, induces diabetes in experimental animals by inducing preferential cytotoxicity in pancreatic beta cells. We investigated whether STZ reduced the production of intracellular insulin through autophagy in insulinoma INS-1E cells. Typically, 2 mM STZ treatment for 24 h significantly decreased cell survival. STZ treatment led to significant decrease in phospho-AMP-activated protein kinase (p-AMPK) level; reduction in levels of phospho-protein kinase R-like endoplasmic reticulum kinase (PERK) and inositol-requiring enzyme 1α (IRE1α); significant reduction in levels of p85α, p110, phospho-serine and threonine kinase/protein kinase B (p-Akt/PKB) (Ser473), phospho-extracellular-regulated kinase (p-ERK), and phospho-mammalian target of rapamycin (p-mTOR); increase in levels of Cu/Zn-superoxide dismutase (SOD), Mn-SOD, and catalase; decrease in B-cell lymphoma 2 (Bcl-2) expression; increase in Bcl-2-associated X protein (Bax) expression; increase in levels of microtubule-associated protein 1 light chain 3 (LC3) and Beclin 1; and reduction in production of intracellular insulin...
February 27, 2018: DNA and Cell Biology
Anna Negroni, Maria Pierdomenico, Salvatore Cucchiara, Laura Stronati
The nucleotide-binding oligomerization domain (NOD) protein, NOD2, belonging to the intracellular NOD-like receptor family, detects conserved motifs in bacterial peptidoglycan and promotes their clearance through activation of a proinflammatory transcriptional program and other innate immune pathways, including autophagy and endoplasmic reticulum stress. An inactive form due to mutations or a constitutive high expression of NOD2 is associated with several inflammatory diseases, suggesting that balanced NOD2 signaling is critical for the maintenance of immune homeostasis...
2018: Journal of Inflammation Research
Wanglong Zheng, Bingjie Wang, Mengxue Si, Hui Zou, Ruilong Song, Jianhong Gu, Yan Yuan, Xuezhong Liu, Guoqiang Zhu, Jianfa Bai, Jianchun Bian, ZongPing Liu
The aim of this study was to investigate the molecular mechanisms of the destruction of cytoskeletal structure by Zearalenone (ZEA) in mouse-derived TM4 cells. In order to investigate the role of autophagy, oxidative stress and endoplasmic reticulum(ER) stress in the process of destruction of cytoskeletal structure, the effects of ZEA on the cell viability, cytoskeletal structure, autophagy, oxidative stress, ER stress, MAPK and PI3K- AKT- mTOR signaling pathways were studied. The data demonstrated that ZEA damaged the cytoskeletal structure through the induction of autophagy that leads to the alteration of cytoskeletal structure via elevated oxidative stress...
February 20, 2018: Scientific Reports
Shariq S Ansari, Ashwini K Sharma, Himanshu Soni, Doaa M Ali, Björn Tews, Rainer König, Hansjörg Eibl, Martin R Berger
Endoplasmic reticulum (ER) plays an essential role in cell function and survival. Accumulation of unfolded or misfolded proteins in the lumen of the ER activates the unfolded protein response (UPR), resulting in ER stress and subsequent apoptosis. The alkylphosphocholine erufosine is a known Akt-mTOR inhibitor in oral squamous cell carcinoma (OSCC). In the present study, we evaluate erufosine's role to induce ER and mitochondrial stress leading to autophagy, apoptosis, and ROS induction. The cellular toxicity of erufosine was determined in two OSCC cell lines and gene expression and enrichment analyses were performed...
February 20, 2018: Cell Death & Disease
Ying-Lan Li, Wen-Feng Cai, Lei Wang, Guan-Sheng Liu, Christian Paul, Lin Jiang, Boyu Wang, Xiang Gao, Yigang Wang, Shi-Zheng Wu
HCLS1 Associated Protein X-1 (HAX1) promotes cell survival through attenuation of the damaged signals from endoplasmic reticulum and mitochondria, which are known as prominent intracellular compartments for the autophagic process under stress conditions. This study investigates whether autophagy can be upregulated in response to HAX1 overexpression and identifies the functional motif in HAX1 responsible for the autophagic induction. Autophagosome accumulation, mitochondrial membrane potential (Δψm), and apoptosis were assessed in HEK293 cells post transduction with full-length or truncated HAX1-encoding genes, while empty vector-transduced cells served as control...
February 20, 2018: DNA and Cell Biology
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