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endoplasmic reticulum and autophagy

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https://www.readbyqxmd.com/read/29142990/the-chemical-chaperone-pba-reduces-er-stress-and-autophagy-and-increases-collagen-iv-%C3%AE-5-expression-in-cultured-fibroblasts-from-men-with-x-linked-alport-syndrome-and-missense-mutations
#1
Dongmao Wang, Mardhiah Mohammad, Yanyan Wang, Rachel Tan, Lydia S Murray, Sharon Ricardo, Hayat Dagher, Tom van Agtmael, Judy Savige
Introduction: X-linked Alport syndrome (OMIM 301050) is caused by COL4A5 missense variants in 40% of families. This study examined the effects of chemical chaperone treatment (sodium 4-phenylbutyrate) on fibroblast cell lines derived from men with missense mutations. Methods: Dermal fibroblast cultures were established from 2 affected men and 3 normals. Proliferation rates were examined, the collagen IV α5 chain localized with immunostaining, and levels of the intra- and extracellular chains quantitated with an in-house enzyme-linked immunosorbent assay...
July 2017: KI Reports
https://www.readbyqxmd.com/read/29141573/liver-protective-effects-of-extra-virgin-olive-oil-interaction-between-its-chemical-composition-and-the-cell-signaling-pathways-involved-in-protection
#2
Sandra A Soto-Alarcon, Rodrigo Valenzuela, Alfonso Valenzuela, Luis A Videla
BACKGROUND AND OBJECTIVE: The liver is an organ susceptible to a multitude of injuries that causes liver damage, like steatosis, non-alcoholic steatohepatitis, cirrhosis, hepatocellular carcinoma, and ischemia-reperfusion injury. Extra virgin olive oil (EVOO), presents several protective effects on the liver, reducing hepatic steatosis, hepatocyte ballooning, fibrogenesis, preventing lipid peroxidation, among other effects. Due to its high levels of monounsaturated fatty acids, mainly oleic acid and phenolic compounds, such as hydroxytyrosol and oleuropein, EVOO is able to participate in the activation of different signaling pathways in the hepatocytes involved in the prevention of inflammation, oxidative stress, endoplasmic reticulum stress, mitochondrial dysfunction, and insulin resistance, allowing the prevention or resolution of liver damage...
November 14, 2017: Endocrine, Metabolic & Immune Disorders Drug Targets
https://www.readbyqxmd.com/read/29137257/kaempferol-induces-hepatocellular-carcinoma-cell-death-via-endoplasmic-reticulum-stress-chop-autophagy-signaling-pathway
#3
Haiqing Guo, Wei Lin, Xiangying Zhang, Xiaohui Zhang, Zhongjie Hu, Liying Li, Zhongping Duan, Jing Zhang, Feng Ren
Kaempferol is a flavonoid compound that has gained widespread attention due to its antitumor functions. However, the underlying mechanisms are still not clear. The present study investigated the effect of kaempferol on hepatocellular carcinoma and its underlying mechanisms. Kaempferol induced autophagy in a concentration- and time-dependent manner in HepG2 or Huh7 cells, which was evidenced by the significant increase of autophagy-related genes. Inhibition of autophagy pathway, through 3-methyladenine or Atg7 siRNA, strongly diminished kaempferol-induced apoptosis...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29135079/cigarette-smoke-extract-and-isoprene-resulted-in-the-induction-of-apoptosis-and-autophagy-in-human-placenta-choriocarcinoma-jeg-3-cells
#4
Hae-Miru Lee, Kyung-Chul Choi
In this study, the effects of cigarette smoke (CS) on the induction of apoptosis via reactive oxygen species (ROS) production and endoplasmic reticulum stress (ER stress) of JEG-3 human choriocarcinoma cells were examined to confirm the relationship between CS and placenta development. Upon TUNEL assay, CS extract (3R4F; 0.3 and 2.1 μM) increased JEG-3 apoptosis. Western blot assay revealed that the protein expressions of p53, Bax, and CCAAT-enhancer-binding protein homologous protein (CHOP) increased, while the levels of Bcl-2 were reduced following CS extract treatment...
November 14, 2017: Environmental Toxicology
https://www.readbyqxmd.com/read/29130967/endoplasmic-reticulum-stress-promotes-autophagy-and-apoptosis-and-reduces-chemotherapy-resistance-in-mutant-p53-lung-cancer-cells
#5
Ping-Ping Gan, Yang-Ying Zhou, Mei-Zuo Zhong, Yun Peng, Li Li, Jian-Huang Li
BACKGROUND/AIMS: Lung cancer (LC) continues to be one of the most prevalent cancers around the world. During this study we aimed to investigate the involvement of endoplasmic reticulum stress (ERS) in autophagy, apoptosis, and chemotherapy resistance of mutant p53 LC cells. METHODS: Immunohistochemistry was employed to help determine the p53 mutation status of cancer cells from 92 primary LC patients, who were subsequently assigned to either the mutant p53 (n = 39) or wild-type p53 group (n = 53)...
November 6, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29130486/rtp801-is-a-critical-factor-in-the-neurodegeneration-process-of-a53t-alpha-synuclein-in-a-mouse-model-of-parkinson-s-disease-under-chronic-restraint-stress
#6
Zhao Zhang, Shi-Feng Chu, Sha-Sha Wang, Yi-Na Jiang, Yan Gao, Peng-Fei Yang, Qi-Di Ai, Nai-Hong Chen
BACKGROUND AND PURPOSE: The incidence of Parkinson's disease exhibited a younger tendency in recent years with the constantly increased stressors of modern society, but this relationship remains obscured. We performed this study to investigate whether stress contributes to this tendency and identify the executor during this process. EXPERIMENTAL APPROACH: Ten-month-old α-synuclein A53T mice, a PD mice model, were treated with chronic restraint stress (CRS) to simulate a PD-sensitive person with constant stress stimulation...
November 11, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29129702/fkbp8-protects-the-heart-from-hemodynamic-stress-by-preventing-the-accumulation-of-misfolded-proteins-and-endoplasmic-reticulum-associated-apoptosis-in-mice
#7
Tomofumi Misaka, Tomokazu Murakawa, Kazuhiko Nishida, Yosuke Omori, Manabu Taneike, Shigemiki Omiya, Chris Molenaar, Yoshihiro Uno, Osamu Yamaguchi, Junji Takeda, Ajay M Shah, Kinya Otsu
Protein quality control in cardiomyocytes is crucial to maintain cellular homeostasis. The accumulation of damaged organelles, such as mitochondria and misfolded proteins in the heart is associated with heart failure. During the process to identify novel mitochondria-specific autophagy (mitophagy) receptors, we found FK506-binding protein 8 (FKBP8), also known as FKBP38, shares similar structural characteristics with a yeast mitophagy receptor, autophagy-related 32 protein. However, knockdown of FKBP8 had no effect on mitophagy in HEK293 cells or H9c2 myocytes...
November 9, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/29127204/mutations-in-the-x-linked-atp6ap2-cause-a-glycosylation-disorder-with-autophagic-defects
#8
Maria A Rujano, Magda Cannata Serio, Ganna Panasyuk, Romain Péanne, Janine Reunert, Daisy Rymen, Virginie Hauser, Julien H Park, Peter Freisinger, Erika Souche, Maria Clara Guida, Esther M Maier, Yoshinao Wada, Stefanie Jäger, Nevan J Krogan, Oliver Kretz, Susana Nobre, Paula Garcia, Dulce Quelhas, Thomas D Bird, Wendy H Raskind, Michael Schwake, Sandrine Duvet, Francois Foulquier, Gert Matthijs, Thorsten Marquardt, Matias Simons
The biogenesis of the multi-subunit vacuolar-type H(+)-ATPase (V-ATPase) is initiated in the endoplasmic reticulum with the assembly of the proton pore V0, which is controlled by a group of assembly factors. Here, we identify two hemizygous missense mutations in the extracellular domain of the accessory V-ATPase subunit ATP6AP2 (also known as the [pro]renin receptor) responsible for a glycosylation disorder with liver disease, immunodeficiency, cutis laxa, and psychomotor impairment. We show that ATP6AP2 deficiency in the mouse liver caused hypoglycosylation of serum proteins and autophagy defects...
November 10, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29117944/small-molecule-sigma1-modulator-induces-autophagic-degradation-of-pd-l1
#9
Christina M Maher, Jeffrey D Thomas, Derick A Haas, Charles G Longen, Halley M Oyer, Jane Y Tong, Felix J Kim
Emerging evidence suggests that Sigma1 (SIGMAR1, also known as sigma-1 receptor) is a unique ligand-regulated integral membrane scaffolding protein that contributes to cellular protein and lipid homeostasis. Previously, we demonstrated that some small molecule modulators of Sigma1 alter endoplasmic reticulum (ER) associated protein homeostasis pathways in cancer cells, including the unfolded protein response and autophagy. Programmed death-ligand 1 (PD-L1) is a type 1 integral membrane glycoprotein that is co-translationally inserted into the ER and is processed and transported through the secretory pathway...
November 8, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29111403/the-critical-role-of-autophagy-in-cadmium-induced-immunosuppression-regulated-by-endoplasmic-reticulum-stress-mediated-calpain-activation-in-raw264-7-mouse-monocytes
#10
Keum-Young So, Byung-Hoon Lee, Seon-Hee Oh
Cadmium (Cd) has toxic and suppressive effects on the immune system, but the underlying mechanisms remain poorly understood. Here, we show that autophagy plays a critical role in regulation of Cd-induced immunosuppression in RAW264.7 cells. Cd decreased cell viability in a dose-dependent manner; cleaved caspase-8, caspase-3, and poly (ADP-ribose) polymerase (PARP)-1; increased DNA laddering; induced CCAAT-enhancer-binding protein homologous protein (CHOP); and reduced tumor necrosis factor (TNF)-α expression; indicating that caspase-dependent and endoplasmic reticulum (ER)-mediated apoptosis are involved in Cd-induced immunotoxicity...
October 27, 2017: Toxicology
https://www.readbyqxmd.com/read/29111283/pancreatic-islet-autonomous-effect-of-arsenic-on-insulin-secretion-through-endoplasmic-reticulum-stress-autophagy-pathway
#11
Wei Wu, Xiaofeng Yao, Liping Jiang, Qiaoting Zhang, Jie Bai, Tianming Qiu, Lei Yang, Ni Gao, Guang Yang, Xiaofang Liu, Min Chen, Xiance Sun
Inorganic arsenic is a worldwide environmental pollutant. Arsenic's relationship with the incidence of diabetes arouses concerns on its etiological mechanism. In this study, the glucose-stimulated insulin secretion (GSIS) from isolated pancreatic islets of As2O3-treated mice was significantly lower than that of control mice. It indicated that the effect of As2O3-inhibited GSIS was pancreatic islet-autonomous. The level of phospho-PERK (p-PERK), a biomarker of endoplasmic reticulum (ER) stress, in pancreas of As2O3-treated mice was increased significantly...
October 27, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/29107114/cancer-chemoprevention-via-activation-of-proteostatic-modules
#12
Aimilia Sklirou, Eleni-Dimitra Papanagnou, Nikolas Fokialakis, Ioannis P Trougakos
Proteins carry out the majority of cellular functions and maintain cellular homeodynamics mostly by participating in multimeric assemblies that operate as protein machines. Proteome quality control is thus critical for cellular functionality, and it is carried out through the curating activity of the proteostasis network (PN). Key components of the PN are the protein synthesis and trafficking modules, the endoplasmic reticulum unfolded protein response, molecular chaperones, and the two main degradation machineries, namely the ubiquitin proteasome and autophagy lysosome pathways...
October 26, 2017: Cancer Letters
https://www.readbyqxmd.com/read/29107113/mir-346-functions-as-a-pro-survival-factor-under-er-stress-by-activating-mitophagy
#13
Junfei Guo, Zhen Yang, Xi Yang, Tong Li, Min Liu, Hua Tang
Stress in the endoplasmic reticulum (ER) triggers the unfolded protein response (UPR), which attempts to restore normal function of the ER. Both autophagy and miRNAs have been reported to participate in the process of ER stress, but the relationship between these two factors is still obscure. In this study, we demonstrated that miR-346, which was induced under ER stress, modulated autophagic flux in HeLa cells. By regulating the process of autophagy, miR-346 reduced the ROS level in the cells, thus protecting them from death following ER stress...
October 26, 2017: Cancer Letters
https://www.readbyqxmd.com/read/29105510/microrna-29a-mitigation-of-endoplasmic-reticulum-and-autophagy-aberrance-counteracts-in-obstructive-jaundice-induced-fibrosis-in-mice
#14
Ying-Hsien Huang, Ya-Ling Yang, Fu-Chen Huang, Mao-Meng Tiao, Yen-Cheng Lin, Ming-Horng Tsai, Feng-Sheng Wang
Hepatic fibrosis was caused by a number of signaling pathways that damage liver integrity. We have previously shown that microRNA-29a (miR-29a) protects against liver fibrosis. Aberrant endoplasmic reticulum (ER) and autophagy function reportedly exaggerate hepatic disorders. The aim of this study was to characterize the biological influence of miR-29a on ER function in injured livers with bile duct ligation (BDL). We performed BDL on miR-29a transgenic mice (miR-29aTg) and wild-type mice to induce cholestatic liver injury...
January 1, 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/29100748/excessive-er-stress-and-the-resulting-autophagic-flux-dysfunction-contribute-to-fluoride-induced-neurotoxicity
#15
Qiang Niu, Jingwen Chen, Tao Xia, Pei Li, Guoyu Zhou, Chunyan Xu, Qian Zhao, Lixin Dong, Shun Zhang, Aiguo Wang
Fluoride is capable of inducing neurotoxicity, but its mechanisms remain elusive. This study aimed to explore the roles of endoplasmic reticulum (ER) stress and autophagy in sodium fluoride (NaF)-induced neurotoxicity, focusing on the regulating role of ER stress in autophagy. The in vivo results demonstrated that NaF exposure impaired the learning and memory capabilities of rats, and resulted in histological and ultrastructural abnormalities in rat hippocampus. Moreover, NaF exposure induced excessive ER stress and associated apoptosis, as manifested by elevated IRE1α, GRP78, cleaved caspase-12 and cleaved-caspase-3, as well as defective autophagy, as shown by increased Beclin1, LC3-II and p62 expression in hippocampus...
October 31, 2017: Environmental Pollution
https://www.readbyqxmd.com/read/29097114/endoplasmic-reticulum-stress-mediated-autophagy-activation-attenuates-fumonisin-b1-induced-hepatotoxicity-in-vitro-and-in-vivo
#16
Mahendra Pal Singh, Sun Chul Kang
Although pathological characteristics of fumonisin B1 are known to induce hepatic injury over prolonged periods, the cellular defense mechanisms against the detrimental effects of FB1 are still unknown. The underlying mechanisms of FB1 toxicity are thought to be related with the inhibition of ceramide synthase, causing an accumulation of sphingoid bases, which in turn cause development of oxidative stress. Herein, we investigated whether autophagy, a cellular defense mechanism, protects liver cells from FB1 exposure...
October 31, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/29076434/cjk-7-a-novel-flavonoid-from-paulownia-tomentosa-triggers-cell-death-cascades-in-hct-116-human-colon-carcinoma-cells-via-redox-signaling
#17
Mahendra Pal Singh, Ki Hun Park, Sun Chul Kang
BACKGROUND: Colon cancer is the second most common cancer to cause death worldwide. About half of colon cancer patients require adjuvant therapy to control relapse following surgical resection. Therefore, abolition of tumor cell progression using an effective chemotherapeutic agent holds a feasible approach to treat patients suffering from colon cancer. In the present study, we evaluated the effects of geranylated flavonoid CJK-7, isolated from Paulownia tomentosa on HCT-116 human colon carcinoma cells...
October 26, 2017: Anti-cancer Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/29074879/the-role-of-autophagy-in-critical-illness-induced-liver-damage
#18
Steven E Thiessen, Inge Derese, Sarah Derde, Thomas Dufour, Lies Pauwels, Youri Bekhuis, Isabel Pintelon, Wim Martinet, Greet Van den Berghe, Ilse Vanhorebeek
Mitochondrial dysfunction and endoplasmic reticulum (ER) stress, which activates the unfolded protein response (UPR), mediate critical illness-induced organ failure, often affecting the liver. Autophagy is known to alleviate both and suppressed or insufficiently activated autophagy in prolonged illness has shown to associate with organ failure. Whether insufficient autophagy contributes to organ failure during critical illness by affecting these underlying mechanisms is incompletely understood. In this study, we investigated whether the inability to acutely activate hepatic autophagy during critical illness aggravates liver damage by increasing hepatic mitochondrial dysfunction and affecting the UPR...
October 26, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29074451/mitochondrial-dysfunction-through-impaired-autophagy-leads-to-endoplasmic-reticulum-stress-deregulated-lipid-metabolism-and-pancreatitis-in-animal-models
#19
Gyorgy Biczo, Eszter T Vegh, Natalia Shalbueva, Olga A Mareninova, Jason Elperin, Ethan Lotshaw, Sophie Gretler, Aurelia Lugea, Sudarshan R Malla, David Dawson, Piotr Ruchala, Julian Whitelegge, Samuel W French, Li Wen, Sohail Z Husain, Fred S Gorelick, Peter Hegyi, Zoltan Rakonczay, Ilya Gukovsky, Anna S Gukovskaya
BACKGROUND & AIMS: Little is known about the signaling pathways that initiate and promote acute pancreatitis (AP). The pathogenesis of AP has been associated with abnormal increases in cytosolic Ca(2+), mitochondrial dysfunction, impaired autophagy, and endoplasmic reticulum (ER) stress. We analyzed the mechanisms of these dysfunctions and their relationships, and how these contribute to development of AP in mice and rats. METHODS: Pancreatitis was induced in C57BL/6J mice (control) and mice deficient in peptidylprolyl isomerase D (cyclophilin D, encoded by Ppid) by administration of L-arginine (also in rats), caerulein, bile acid, or an AP-inducing diet...
October 23, 2017: Gastroenterology
https://www.readbyqxmd.com/read/29074393/dcf1-subcellular-localization-and-its-function-in-mitochondria
#20
Yanlu Chen, Ruili Feng, Guanghong Luo, Jianjian Guo, Yajiang Wang, Yangyang Sun, Lili Zheng, Tieqiao Wen
Dendritic cell factor 1 (DCF1) is a transmembrane protein that plays important roles in regulating neural stem cell differentiation and dendritic spine formation. Apart from its cytoplasmic functions, DCF1 plays a role in autophagy during the regulation of amyloid precursor proteins. However, the subcellular localization of DCF1 remains unknown. Therefore, in this study, DCF1 tagged with green fluorescent protein was transiently expression in HelaS3 and HEK293T cells. The results showed that DCF1 was widely expressed in different organelles, including the mitochondria, Golgi apparatus, endoplasmic reticulum, endosomes and lysosomes...
October 23, 2017: Biochimie
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