endoplasmic reticulum and autophagy

Junhee Kwon, Yunkyeong Lee, Ji Hye Jeong, Jae-Ha Ryu, Keun Il Kim
Relationship between autophagy and endoplasmic reticulum (ER) stress and their application to treat cancer have been actively studied these days. Recently, a lignan [(-)-(2R, 3R)-1,4-O-diferuloylsecoisolariciresinol, DFS] from Alnus japonica has been found to reduce the viability of colon cancer cells. In this study, we have observed DFS-induced autophagy in a variety of cancer cell lines. In addition, DFS led to ER stress, based on the activation of unfolded protein response (UPR) transducers and an elevated expression of UPR target genes in prostate and colon cancer cells...
March 21, 2020: Biochemical and Biophysical Research Communications
David M Hollenstein, Claudine Kraft
Autophagy is characterized by the formation of double-membrane vesicles called autophagosomes, which deliver bulk cytoplasmic material to the lytic compartment of the cell for degradation. Autophagosome formation is initiated by assembly and recruitment of the core autophagy machinery to distinct cellular sites, referred to as phagophore assembly sites (PAS) in yeast or autophagosome formation sites in other organisms. A large number of autophagy proteins involved in the formation of autophagosomes has been identified; however, how the individual components of the PAS are assembled and how they function to generate autophagosomes remains a fundamental question...
March 20, 2020: Current Opinion in Cell Biology
A Silva-Palacios, C Zazueta, J Pedraza-Chaverri
Cardiovascular system cell biology is tightly regulated and mitochondria play a relevant role in maintaining heart function. In recent decades, associations between such organelles and the sarco/endoplasmic reticulum (SR) have been raised great interest. Formally identified as mitochondria-associated SR membranes (MAMs), these structures regulate different cellular functions, including calcium management, lipid metabolism, autophagy, oxidative stress, and management of unfolded proteins. In this review, we highlight MAMs' alterations mainly in cardiomyocytes, linked with cardiovascular diseases, such as cardiac ischemia-reperfusion, heart failure, and dilated cardiomyopathy...
March 18, 2020: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
Tyler G Lewy, Danielle K Offerdahl, Jeffrey M Grabowski, Eliza Kellman, Luwanika Mlera, Abhilash Chiramel, Marshall E Bloom
The unfolded protein response (UPR) maintains protein-folding homeostasis in the endoplasmic reticulum (ER) and has been implicated as both beneficial and detrimental to flavivirus infection. Protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK), a sensor of the UPR, is commonly associated with antiviral effects during mosquito-borne flavivirus (MBFV) infection, but its relation to tick-borne flavivirus (TBFV) infection remains largely unexplored. In this study, we identified changes in UPR and autophagic activity during Langat virus (LGTV) infection...
March 18, 2020: Viruses
Jian Gu, Tao Zhang, Jianrong Guo, Ke Chen, Huili Li, Jiliang Wang
Hepatic ischemia/reperfusion (I/R) injury is a major concern in liver surgery settings. Mitochondria are critical targets or the origin of tissue injury, particularly I/R injury. Mitophagy, a selective form of autophagy, is a fundamental process that removes damaged or unwanted mitochondria for mitochondrial quality control, but its role in hepatic I/R remains unclear. In the present study, we investigated the role of mitophagy in hepatic I/R by focusing on PTEN-induced putative kinase 1 (PINK1). Livers from 10-week-old mice and primary hepatocytes were subjected to in vivo hepatic I/R and in vitro hypoxia-reoxygenation (H/R), respectively...
March 17, 2020: Shock
Zeping Xu, Yanqing Wu, Fan Wang, Xiaofeng Li, Ping Wang, Yuying Li, Junnan Wu, Yiyang Li, Ting Jiang, Xindian Pan, Xie Zhang, Longteng Xie, Jian Xiao, Yanlong Liu
Background: Type 2 diabetes (T2D) is a metabolic dysfunction disease that causes several complications. Liver injury is one of these that severely affects patients with diabetes. Fibroblast growth factor 1 (FGF1) has glucose-lowering activity and plays a role in modulation of several liver injuries. Nevertheless, the effects and potential mechanisms of FGF1 against diabetes-induced liver injury are unknown. Methods: To further investigate the effect of FGF1 on diabetic liver injury, we divided db/db mice into two groups and intraperitoneally (i...
2020: Frontiers in Pharmacology
Qicheng Zhang, Mengmeng Chen, Limin Cao, Yinghui Ren, Xueru Guo, Xiang Wu, Ke Xu
Isothiocyanates (ITCs) are natural compounds abundant in cruciferous vegetables. Numerous studies have shown that ITCs exhibit anticancer activity by affecting multiple pathways including apoptosis and oxidative stress, and are expected to be developed into novel anticancer drugs. In our previous studies, we demonstrated that ITCs effectively inhibit the proliferation of non-small cell lung cancer (NSCLC) cells, also induce apoptosis and autophagy. In the present study, we found that phenethyl isothiocyanate (PEITC) had significant synergistic effects with epidermal growth factor receptor tyrosine kinase inhibitor Gefitinib in NSCLC cell lines NCI-H1299 and SK-MES-1; and the degradation of antiapoptotic factor myeloid cell leukemia 1 (Mcl-1) caused by PEITC treatment played key roles in the sensitivity of NSCLC cells to Gefitinib...
March 18, 2020: Molecular Carcinogenesis
Dong-Jae Jun, Marc M Schumacher, Seonghwan Hwang, Lisa N Kinch, Nick V Grishen, Russell A DeBose-Boyd
Mutations in UbiA prenyltransferase domain-containing protein-1 (UBIAD1), a prenyltransferase that uses geranylgeranyl pyrophosphate (GGpp) to synthesize the vitamin K2 subtype menaquinone-4 (MK-4), cause Schnyder corneal dystrophy (SCD).  This autosomal-dominant disorder is characterized by opacification of the cornea that results from abnormal accumulation of cholesterol in the tissue.  We previously discovered that sterols trigger binding of UBIAD1 to endoplasmic reticulum (ER)-localized HMG CoA reductase, the rate-limiting enzyme in the synthesis of cholesterol and nonsterol isoprenoids, including GGpp...
March 18, 2020: Journal of Lipid Research
Changfeng Li, Ying Zhang, Jiao Liu, Rui Kang, Daniel J Klionsky, Daolin Tang
Pancreatic cancer tends to be highly resistant to current therapy and remains one of the great challenges in biomedicine with very low 5-year survival rates. Here, we report that zalcitabine, an antiviral drug for human immunodeficiency virus infection, can suppress the growth of primary and immortalized human pancreatic cancer cells through the induction of ferroptosis, an iron-dependent form of regulated cell death. Mechanically, this effect relies on zalcitabine-induced mitochondrial DNA stress, which activates the STING1/TMEM173-mediated DNA sensing pathway, leading to macroautophagy/autophagy-dependent ferroptotic cell death via lipid peroxidation, but not a type I interferon response...
March 18, 2020: Autophagy
Ji-Hua Lin, Sheng-Yi Chen, Chi-Cheng Lu, Jer-An Lin, Gow-Chin Yen
Gemcitabine (GEM) resistance in pancreatic adenocarcinoma mediated by the receptor for advanced glycation end products (RAGE) has been demonstrated. Therefore, investigating the safety and the potential of new auxiliary methods for pancreatic cancer treatment is urgent. Ursolic acid (UA), a natural pentacyclic triterpenoid found in apple peels, rosemary, and thyme, has been reported to have anticancer capacity. This study aimed to reveal the underlying mechanisms of UA in cell death and drug enhancement, especially in GEM-resistant pancreatic cancer cells...
March 17, 2020: Phytotherapy Research: PTR
Yongda Liu, Shuang Wang, Zhibin Wang, Mengmeng Ding, Xingyue Li, Jiao Guo, Guang Han, Ping Zhao
Studies demonstrated that spinal autophagy was impaired in spinal nerve ligation (SNL) rats. However, the relationship of endoplasmic reticulum (ER) stress and ER-phagy and whether dexmedetomidine (DEX) modulates ER-phagy remain unclear. In this study, male Sprague-Dawley (SD) rats and the SNL animal model were used. 4-Phenylbutyric acid (4-PBA), tunicamycin (TM), rapamycin (RAP), and 3-methyladenine (3-MA) were intrathecally administered, respectively to demonstrate the relationship of ER stress and ER-phagy...
2020: Frontiers in Neuroscience
Erdi Sozen, Burak Yazgan, Olgu Enis Tok, Tugce Demirel, Feriha Ercan, Jonathan D Proto, Nesrin Kartal Ozer
BACKGROUND: Cardiovascular diseases (CVDs), with highest mortality and morbidity rates, are the major cause of death in the world. Due to the limited information on heart tissue changes, mediated by hypercholesterolemia, we planned to investigate molecular mechanisms of endoplasmic reticulum (ER) stress and related cell death in high cholesterol fed rabbit model and possible beneficial effects of α-tocopherol. METHODS: Molecular changes in rabbit heart tissue and cultured cardiomyocytes (H9c2 cells) were measured by western blotting, qRT-PCR, immunflouresence and flow cytometry experiments...
March 14, 2020: Metabolism: Clinical and Experimental
Jorge Montesinos, Estela Area-Gomez
Organelles within cells are interconnected by physical associations or contact sites. In the last decade, many reports have shown that these interactions are functional domains that maintain cellular homeostasis. One of the best studied interactions is between endoplasmic reticulum (ER) and mitochondria via mitochondria-associated membranes or MAMs. MAMs are lipid rafts in the ER in close apposition to mitochondria, where multiple enzymatic activities converge to coordinately regulate cellular functions such as: the import of phosphatidylserine into mitochondria from the ER for decarboxylation to phosphatidylethanolamine, cholesterol esterification, calcium signaling, mitochondrial shape and motility, autophagy and apoptosis...
2020: Methods in Cell Biology
Neha Shrestha, Tongyu Liu, Yewei Ji, Rachel Reinert, Mauricio Torres, Xin Li, Maria Zhang, Chih-Hang Anthony Tang, Chih-Chi Andrew Hu, Chengyang Liu, Ali Naji, Ming Liu, Jiandie D Lin, Sander Kersten, Peter Arvan, Ling Qi
β-cell apoptosis and dedifferentiation are two hotly-debated mechanisms underlying β-cell loss in type 2 diabetes; however, the molecular drivers underlying such events remain largely unclear. Here, we performed a side-by-side comparison of mice carrying β-cell-specific deletion of endoplasmic reticulum (ER)-associated degradation (ERAD) and autophagy. We reported that while autophagy was necessary for β-cell survival, the highly conserved Sel1L-Hrd1 ERAD protein complex was required for the maintenance of β-cell maturation and identity...
March 17, 2020: Journal of Clinical Investigation
Norah M Alzamil, Faten A Alradini, Bahjat Al-Ani, Sheren Younes, Maha Fahad Saja, Samaa S Kamar, Amal F Dawood
We sought to determine whether TDZD-8, the inhibitor of the glycogen synthase kinase-3β (GSK3β) can protect the synovial membrane of the knee joint against injuries induced by collagen type II immunization (CIA) possibly via the downregulation of synovial leukocyte infiltration, endoplasmic reticulum stress (ERS), and autophagy. The model group of rats (CIA) were immunized over a period of three weeks with collagen type II, whereas the treated group of rats (CIA+TDZD-8) were treated with TDZD-8 (1 mg/kg) for 21 days after the completion of the immunization regimen...
March 17, 2020: Clinical and Experimental Pharmacology & Physiology
Zhenyu Wang, Shengxiong Zheng, Yang Gu, Linquan Zhou, Bin Lin, Wenge Liu
OBJECTIVE: To investigate mechanism of endoplasmic reticulum (ER) stress-mediated autophagy in spinal cord injury (SCI). METHODS: An in vitro model of spinal cord injury(SCI)was established by recombinant human beta nerve growth factor (NGF)-induced PC12 cells. Immunofluorescence was used to detect properties of PC12 cells induced by NGF. Western blot assay was used to detect expressions of the autophagy-related protein microtubule-associated protein 1 light chain 3 (LC3)I/II, the ER stress-related protein (HSPA5/GRP78) as well as the PI3K/AKT/mTOR signaling pathway-related proteins after mechanical injury at different time points...
March 13, 2020: World Neurosurgery
Hyun-Kyoung Kim, Geum-Hwa Lee, Kashi Raj Bhattarai, Myung-Shik Lee, Sung Hoon Back, Hyung-Ryong Kim, Han-Jung Chae
Lysosomal Ca2+ contributes to macroautophagy/autophagy, an intracellular process for the degradation of cytoplasmic material and organelles in the lysosomes to protect cells against stress responses. TMBIM6 (transmembrane BAX inhibitor motif containing 6) is a Ca2+ channel-like protein known to regulate ER stress response and apoptosis. In this study, we examined the as yet unknown role of TMBIM6 in regulating lysosomal Ca2+ levels. The Ca2+ efflux from the ER through TMBIM6 was found to increase the resting lysosomal Ca2+ level, in which ITPR-independent regulation of Ca2+ status was observed...
March 13, 2020: Autophagy
Jiao Liu, Feimei Kuang, Guido Kroemer, Daniel J Klionsky, Rui Kang, Daolin Tang
Macroautophagy (hereafter referred to as autophagy) is an evolutionarily conserved cellular process capable of degrading various biological molecules (e.g., protein, glycogen, lipids, DNA, and RNA) and organelles (e.g., mitochondria, endoplasmic reticulum [ER] ribosomes, lysosomes, and micronuclei) via the lysosomal pathway. Ferroptosis is a type of oxidative stress-dependent regulated cell death associated with iron accumulation and lipid peroxidation. The recently discovered role of autophagy, especially selective types of autophagy (e...
March 3, 2020: Cell Chemical Biology
N S Farag, U Breitinger, H G Breitinger, M A El Azizi
Viroporins are virus encoded proteins that alter membrane permeability and can trigger subsequent cellular signals. Oligomerization of viroporin subunits results in formation of a hydrophilic pore which facilitates ion transport across host cell membranes. These viral channel proteins may be involved in different stages of the virus infection cycle. Inflammasomes are large multimolecular complexes best recognized for their ability to control activation of caspase-1, which in turn regulates the maturation of interleukin-1 β (IL-1β) and interleukin 18 (IL-18)...
March 7, 2020: International Journal of Biochemistry & Cell Biology
Kai Yin, Yuan Cui, Yingying Qu, Jinxi Zhang, Hongfu Zhang, Hongjin Lin
Hydrogen sulfide (H2 S) is a toxic air pollutant that causes immune damage. Recent studies have found that neutrophil extracellular trap (NET) formation is one way in which neutrophils exert immune functions. In addition, the formation of NETs is also related to thrombosis and autoimmune diseases. Recent studies have shown that miRNAs are involved in the regulation of a variety of pathophysiological processes. Here, we investigated the role of H2 S in regulating the formation of NETs by affecting miR-16-5p...
March 7, 2020: Ecotoxicology and Environmental Safety
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