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endoplasmic reticulum

Xin Zhou, Dewu Han, Ruiling Xu, Huiwen Wu, Chongxiao Qu, Feng Wang, Xiangyu Wang, Yuanchang Zhao
We set out to explore the hypothesis that glycine attenuates non-alcoholic steatohepatitis (NASH) in rats and the possible mechanism by which is it does. Male Sprague-Dawley (SD) rats were fed a diet containing high fat and high sucrose (HSHF) for 24 weeks to induce NASH. Blood and liver tissues were sampled at selected time points throughout the study. Compared with control animals, the content of alanine transaminase (ALT), triglycerides (TGs), and free fatty acids (FFAs) in plasma and the TG and FFA content in the liver was increased from week 4 to 24...
October 23, 2016: Oncotarget
Nuno Miguel Luis, Lifen Wang, Mauricio Ortega, Hansong Deng, Subhash D Katewa, Patrick Wai-Lun Li, Jason Karpac, Heinrich Jasper, Pankaj Kapahi
Dietary restriction (DR) is one of the most robust lifespan-extending interventions in animals. The beneficial effects of DR involve a metabolic adaptation toward increased triglyceride usage. The regulatory mechanism and the tissue specificity of this metabolic switch remain unclear. Here, we show that the IRE1/XBP1 endoplasmic reticulum (ER) stress signaling module mediates metabolic adaptation upon DR in flies by promoting triglyceride synthesis and accumulation in enterocytes (ECs) of the Drosophila midgut...
October 25, 2016: Cell Reports
Douglas Matsunaga, Parameswaran G Sreekumar, Keijiro Ishikawa, Hiroto Terasaki, Ernesto Barron, Pinchas Cohen, Ram Kannan, David R Hinton
Humanin (HN) is a small mitochondrial-encoded peptide with neuroprotective properties. We have recently shown protection of retinal pigmented epithelium (RPE) cells by HN in oxidative stress; however, the effect of HN on endoplasmic reticulum (ER) stress has not been evaluated in any cell type. Our aim here was to study the effect of HN on ER stress-induced apoptosis in RPE cells with a specific focus on ER-mitochondrial cross-talk. Dose dependent effects of ER stressors (tunicamycin (TM), brefeldin A, and thapsigargin) were studied after 12 hr of treatment in confluent primary human RPE cells with or without 12 hr of HN pretreatment (1-20 μg/mL)...
2016: PloS One
Chao Zhang, Chendan Wang, Jianbo Ren, Xiangjie Guo, Keming Yun
Glutamate is not only a neurotransmitter but also an important neurotoxin in central nervous system (CNS). Chronic elevation of glutamate induces both neuronal and glial cell apoptosis. However, its effect on astrocytes is complex and still remains unclear. In this study, we investigated whether morphine, a common opioid ligand, could affect glutamate-induced apoptosis in astrocytes. Primary cultured astrocytes were incubated with glutamate in the presence/absence of morphine. It was found that morphine could reduce glutamate-induced apoptosis of astrocytes...
October 24, 2016: International Journal of Molecular Sciences
Yan Sun, Ping-An Peng, Yue Ma, Xiaoli Liu, Yi Yu, Shuo Jia, Xiaohan Xu, Sijing Wu, Yujie Zhou
Contrast-induced acute kidney injury (CI-AKI) is a serious complication of the administration of iodinated contrast media (CM) for diagnostic and interventional cardiovascular procedures and is associated with substantial morbidity and mortality. While the preventative measures can mitigate the risk of CI-AKI, there remains a need for novel and effective therapeutic approaches. The pathogenesis of CI-AKI is complex and not completely understood. CM-induced renal tubular cell apoptosis caused by the activation of endoplasmic reticulum (ER) stress is involved in CI-AKI...
October 25, 2016: Current Vascular Pharmacology
Giovanni Corsetti, Evasio Pasini, Tiziano M Scarabelli, Claudia Romano, Pratik R Agrawal, Carol Chen-Scarabelli, Richard Knight, Louis Saravolatz, Jagat Narula, Mario Ferrari-Vivaldi, Vincenzo Flati, Deodato Assanelli, Francesco S Dioguardi
BACKGROUND: Klotho proteins (α- and β) are membrane-based circulating proteins that regulate cell metabolism, as well as the lifespan modulating activity of Fibroblast Growth Factors (FGFs). Recent data has shown that higher plasma circulating Klotho levels reduce cardiovascular risk, suggesting Klotho has a protective role in cardiovascular diseases. However, although so far it has been identified in various organs, it is unknown whether cardiomyocytes express Klotho and FGFs, and whether high cardiovascular risk could affect cardiac expression of Klotho, FGFs and other molecules...
August 2016: Journal of Geriatric Cardiology: JGC
Jeong Su Park, Sue Young Oh, Da Hyun Lee, Yu Seol Lee, Su Haeng Sung, Hye Won Ji, Moon Joo Lee, Yong-Ho Lee, Sue Goo Rhee, Soo Han Bae
Endoplasmic reticulum (ER) stress is triggered by various cellular stresses that disturb protein folding or calcium homeostasis in the ER. To cope with these stresses, ER stress activates the unfolded protein response (UPR) pathway, but unresolved ER stress induces reactive oxygen species (ROS) accumulation leading to apoptotic cell death. However, the mechanisms that underlie protection from ER stress-induced cell death are not clearly defined. The nuclear factor erythroid 2-related factor 2 (Nrf2)-Kelch-like ECH-associated protein 1 (Keap1) pathway plays a crucial role in the protection of cells against ROS-mediated oxidative damage...
October 26, 2016: Free Radical Research
Catherine L Jackson, Laurence Walch, Jean-Marc Verbavatz
An evolutionarily conserved feature of cellular organelles is the distinct phospholipid composition of their bounding membranes, which is essential to their identity and function. Within eukaryotic cells, two major lipid territories can be discerned, one centered on the endoplasmic reticulum and characterized by membranes with lipid packing defects, the other comprising plasma-membrane-derived organelles and characterized by membrane charge. We discuss how this cellular lipid organization is maintained, how lipid flux is regulated, and how perturbations in cellular lipid homeostasis can lead to disease...
October 24, 2016: Developmental Cell
Wenjie Li, Fei Cao, Juan Li, Zhixin Wang, Yu Ren, Zheyong Liang, Peijun Liu
Simvastatin (SIM), a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, has been reported to inhibit the activity of hepatitis B virus (HBV), however, the mechanism underlying its antiviral function remains unknown. Minichromosome maintenance (MCM) 7, a component of the MCM complex, has been reported to act as an important host factor aiding virus genome replication in host cells. The present study demonstrated that downregulation of MCM7 inhibited the expression of proteins transferred by adenoviral vectors...
October 20, 2016: Molecular Medicine Reports
H Viisanen, H Chapman, H Wei, M Lasierra Losada, A Koivisto, K E Akerman, A Pertovaara
Methylglyoxal (MG) is a reactive carbonyl compound generated in diabetes mellitus. MG is an established transient receptor potential ankyrin 1 (TRPA1) channel agonist that contributes to TRPA1-mediated diabetic pain hypersensitivity. Here we studied whether exposure to diabetes and thereby to elevated endogenous MG modulates hypersensitivity induced by intradermal MG. Moreover, since diabetes induces endoplasmic reticulum (ER) stress, we compared the role of TRPA1 in diabetes and ER stress by assessing whether tunicamycin-induced ER stress, without diabetes, produces TRPA1-mediated pain hypersensitivity and by assessing whether ER stress and diabetes have similar modulatory effects on MG-induced hypersensitivity...
August 2016: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
Arshag D Mooradian
The availability of effective drugs targeting the major risk factors of cardiovascular disease (CVD) has reduced morbidity and mortality. Cumulative relative risk of CVD events can be reduced by 75 % with a combination of aspirin, a β-adrenoceptor antagonist (β-blocker), an HMG-CoA reductase inhibitor (statin), and an angiotensin-converting enzyme inhibitor. The principal pharmacodynamics of these drugs cannot explain the entirety of their cardioprotective action, as other drugs with similar pharmacologic targets have not been associated with favorable clinical effects...
October 24, 2016: American Journal of Cardiovascular Drugs: Drugs, Devices, and Other Interventions
Bose Karthikeyan, Lakshminarasimhan Harini, Vaithilingam Krishnakumar, Velu Rajesh Kannan, Krishnan Sundar, Thandavarayan Kathiresan
Endoplasmic reticulum (ER) stress-mediated apoptosis is a well-known factor in the pathogenesis of age-related macular degeneration (AMD). ER stress leads to accumulation of misfolded proteins, which in turn activates unfolded protein response (UPR) of the cell for its survival. The prolonged UPR of ER stress promotes cell death; however, the transition between adaptation and ER stress-induced apoptosis has not been clearly understood. Hence, the present study investigates the regulatory effect of (-)-epigallocatechin gallate (EGCG) on ER stress-induced by hydrogen peroxide (H2O2) and disturbance of calcium homeostasis by thapsigargin (TG) in mouse retinal pigment epithelial (MRPE) cells...
October 24, 2016: Apoptosis: An International Journal on Programmed Cell Death
Chen-Bin Yu, Guo-Long Zhao, Li-Ming Yu, Shi-Qiang Yu, Wei-Xun Duan, Hai-Feng Zhang
The present study was aimed to investigate the underlying mechanisms of the protective effect of proanthocyanidin (Pro) against hypoxia/reoxygenation (H/R) injury in H9C2 cells with a focus on Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway. H9C2 cells were randomly assigned to 5 groups, including the control group (Con), the H/R-injured group (H/R), the Pro-treated group (H/R+Pro), the JAK2 siRNA-treated group (H/R+Pro+JAK2 siRNA) and the JAK2 siRNA control group (H/R+JAK2 siRNA)...
October 25, 2016: Sheng Li Xue Bao: [Acta Physiologica Sinica]
Dilip Sharma, Jitendra Narain Singh, Shyam S Sharma
Mechanisms and pathways involving in diabetic neuropathy are still not fully understood but can be unified by the process of overproduction of reactive oxygen species (ROS) such as superoxide, endoplasmic reticulum (ER) stress, downstream intracellular signaling pathways and their modulation. Susceptibility of dorsal root ganglion (DRG) to internal/external hyperglycemic environment stress contributes to the pathogenesis and progression of diabetic neuropathy. ER stress leads to abnormal ion channel function, gene expression, transcriptional regulation, metabolism and protein folding...
October 21, 2016: Neuroscience Letters
John D Hulleman, Joseph C Genereux, Annie Nguyen
Fibulin-3 (F3) is an important, disulfide-rich, extracellular matrix glycoprotein that has been associated with a number of diseases ranging from cancer to retinal degeneration. An Arg345Trp (R345W) mutation in F3 causes the rare, autosomal dominant macular dystrophy, Malattia Leventinese. The purpose of this study was to identify and validate novel intracellular interacting partners of wild-type (WT) and R345W F3 in retinal pigment epithelium cells. We used stable isotope labeling by amino acids in cell culture (SILAC) to generate 'heavy' and 'light' isotopically labeled ARPE-19 cell populations which were subsequently infected with adenovirus encoding for FLAG-tagged (FT) WT or R345W F3...
October 21, 2016: Experimental Eye Research
Russell Dahl
Endoplasmic reticulum (ER) stress is intimately linked to Parkinson's disease (PD) pathophysiology. Disrupted intracellular calcium homeostasis is a major cause of the ER stress seen in dopaminergic neurons, leading to the cell death and subsequent loss of movement and coordination in patients. Dysfunctional calcium handling proteins play a major role in the promulgation of ER stress in PD. Specifically, compromised sarco/endoplasmic reticulum Ca(2+)-ATPase (SERCA) has been identified as a major cause of ER stress and neuron loss in PD...
October 12, 2016: Bioorganic & Medicinal Chemistry
Anna Hojka-Osinska, Lucyna Budzko, Agnieszka Zmienko, Agnieszka Rybarczyk, Patrick Maillard, Agata Budkowska, Marek Figlerowicz, Paulina Jackowiak
Hepatitis C virus (HCV) infection is one of the major causes of chronic liver diseases. Unfortunately, the mechanisms of HCV infection-induced liver injury and host-virus interactions are still not well recognized. To better understand these processes we determined the changes in the host gene expression that occur during HCV infection of Huh-7.5 cells. As a result, we identified genes that may contribute to the immune and metabolic cellular responses to infection. Pathway enrichment analysis indicated that HCV induced an increased expression of genes involved in mitogen-activated protein kinases signaling, adipocytokine signaling, cell cycle and nitrogen metabolism...
October 25, 2016: Acta Biochimica Polonica
Toshiyuki Yamaji, Aya Horie, Yuriko Tachida, Chisato Sakuma, Yusuke Suzuki, Yasunori Kushi, Kentaro Hanada
Ceramide is a common precursor of sphingomyelin (SM) and glycosphingolipids (GSLs) in mammalian cells. Ceramide synthase 2 (CERS2), one of the six ceramide synthase isoforms, is responsible for the synthesis of very long chain fatty acid (C20-26 fatty acids) (VLC)-containing ceramides (VLC-Cer). It is known that the proportion of VLC species in GSLs is higher than that in SM. To address the mechanism of the VLC-preference of GSLs, we used genome editing to establish three HeLa cell mutants that expressed different amounts of CERS2 and compared the acyl chain lengths of SM and GSLs by metabolic labeling experiments...
October 21, 2016: International Journal of Molecular Sciences
Miao Long, Yi Liu, Yu Cao, Nan Wang, Meng Dang, Jianbin He
Lead is harmful for human health and animals. Proanthocyanidins (PCs), a natural antioxidant, possess a broad spectrum of pharmacological and medicinal properties. However, its protective effects against lead-induced liver damage have not been clarified. This study was aimed to evaluate the protective effect of PCs on the hepatotoxicity of male Kunming mice induced by chronic lead exposure. A total of 70 healthy male Kunming mice were averagely divided into four groups: control group, i.e., the group exposed to lead, the group treated with PCs, and the group co-treated with lead and PCs...
October 21, 2016: Nutrients
Harun-Or Rashid, Hyun-Kyoung Kim, Raghupatil Junjappa, Hyung-Ryong Kim, Han-Jung Chae
Compromised protein folding capacity in the endoplasmic reticulum (ER) leads to a protein traffic jam that produces a toxic environment called ER stress. However, the ER smartly handles such a critical situation by activating a cascade of proteins responsible for sensing and responding to the noxious stimuli of accumulated proteins. The ER protein load is higher in secretory cells, such as liver hepatocytes, which are thus prone to stress-mediated toxicity and various diseases, including alcohol-induced liver injury, fatty liver disease, and viral hepatitis...
October 23, 2016: Journal of Gastroenterology and Hepatology
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