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endoplasmic reticulum and autophagy

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https://www.readbyqxmd.com/read/28548902/er-mitochondria-signaling-regulates-autophagy
#1
Patricia Gomez-Suaga, Sebastien Paillusson, Christopher C J Miller
The endoplasmic reticulum (ER) and mitochondria form tight functional contacts that regulate a number of key cellular processes. The formation of these contacts involves "tethering proteins" that function to recruit regions of ER to mitochondria. The integral ER protein VAPB (VAMP associated protein B and C) binds to the outer mitochondrial membrane protein, RMDN3/PTPIP51 (regulator of microtubule dynamics 3) to form one such set of tethers. Recently, we showed that the VAPB-RMDN3 tethers regulate macroautophagy/autophagy...
May 26, 2017: Autophagy
https://www.readbyqxmd.com/read/28548464/control-of-cell-death-and-mitochondrial-fission-by-erk1-2-map-kinase-signalling
#2
REVIEW
Simon J Cook, Kate Stuart, Rebecca Gilley, Matthew J Sale
The ERK1/2 signalling pathway is best known for its role in connecting activated growth factor receptors to changes in gene expression due to activated ERK1/2 entering the nucleus and phosphorylating transcription factors. However, active ERK1/2 also translocate to a variety of other organelles including the endoplasmic reticulum, endosomes, golgi and mitochondria to access specific substrates and influence cell physiology. In this article we review two aspects of ERK1/2 signalling at the mitochondria that are involved in regulating cell fate decisions...
May 26, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28544790/roles-of-autophagy-and-endoplasmic-reticulum-stress-in-intracerebral-hemorrhage-induced-secondary-brain-injury-in%C3%A2-rats
#3
Xiao-Chun Duan, Wei Wang, Dong-Xia Feng, Jia Yin, Gang Zuo, Dong-Dong Chen, Zhou-Qing Chen, Hai-Ying Li, Zhong Wang, Gang Chen
OBJECTIVES: This study aimed to evaluate the roles of autophagy and endoplasmic reticulum (ER) stress in intracerebral hemorrhage (ICH)-induced secondary brain injury (SBI) in rats. METHODS: Autophagy inducer (rapamycin) and inhibitor (3-methyladenine), as well as ER stress activator (tunicamycin, TM) and inhibitor (tauroursodeoxycholic acid, TUDCA), were used. Bafilomycin A1, an inhibitor of autophagosome-lysosome fusion, was used to assess autophagic flux. RESULTS: Autophagy and ER stress were enhanced in the week after ICH...
May 19, 2017: CNS Neuroscience & Therapeutics
https://www.readbyqxmd.com/read/28540288/recent-insights-into-the-role-of-unfolded-protein-response-in-er-stress-in-health-and-disease
#4
REVIEW
Dan Lindholm, Laura Korhonen, Ove Eriksson, Sulev Kõks
Unfolded stress response (UPR) is a conserved cellular pathway involved in protein quality control to maintain homeostasis under different conditions and disease states characterized by cell stress. Although three general schemes of and genes induced by UPR are rather well-established, open questions remain including the precise role of UPR in human diseases and the interactions between different sensor systems during cell stress signaling. Particularly, the issue how the normally adaptive and pro-survival UPR pathway turns into a deleterious process causing sustained endoplasmic reticulum (ER) stress and cell death requires more studies...
2017: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/28539871/protein-quality-control-and-the-amyotrophic-lateral-sclerosis-frontotemporal-dementia-continuum
#5
Hamideh Shahheydari, Audrey Ragagnin, Adam K Walker, Reka P Toth, Marta Vidal, Cyril J Jagaraj, Emma R Perri, Anna Konopka, Jessica M Sultana, Julie D Atkin
Protein homeostasis, or proteostasis, has an important regulatory role in cellular function. Protein quality control mechanisms, including protein folding and protein degradation processes, have a crucial function in post-mitotic neurons. Cellular protein quality control relies on multiple strategies, including molecular chaperones, autophagy, the ubiquitin proteasome system, endoplasmic reticulum (ER)-associated degradation (ERAD) and the formation of stress granules (SGs), to regulate proteostasis. Neurodegenerative diseases are characterized by the presence of misfolded protein aggregates, implying that protein quality control mechanisms are dysfunctional in these conditions...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28537930/3-decylcatechol-induces-autophagy-mediated-cell-death-through-the-ire1%C3%AE-jnk-p62-in-hepatocellular-carcinoma-cells
#6
Da-Hye Go, Yu Geon Lee, Da-Hye Lee, Jin-A Kim, In-Hwa Jo, Yeon Soo Han, Yong Hun Jo, Kwang-Youn Kim, Young-Kyo Seo, Jae-Hak Moon, Chang Hwa Jung, Tae-Il Jeon
The natural, phenolic lipid urushiol exhibits both antioxidant and anticancer activities; however, its biological activity on hepatocellular carcinoma (HCC) has not been previously investigated. Here, we demonstrate that an urushiol derivative, 3-decylcatechol (DC), induces human HCC Huh7 cell death by induction of autophagy. DC initiates the autophagic process by activation of the mammalian target of rapamycin signaling pathway via Unc-51-like autophagy activating kinase 1, leading to autophagosome formation...
May 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28537902/endoplasmic-reticulum-stress-promotes-autophagy-and-apoptosis-and-reverses-chemoresistance-in-human-ovarian-cancer-cells
#7
Jin-Long Hu, Xin-Long Hu, Ai-Ye Guo, Chao-Jie Wang, Yi-Yang Wen, Shun-Dong Cang
Ovarian cancer presents the highest mortality rate among gynecological tumors. Here, we measured cell viability, proliferation, apoptosis, autophagy, and expression of endoplasmic reticulum stress (ERS)-related proteins, PI3K/AKT/mTOR pathway-related proteins, and apoptosis- and autophagy-related proteins in SKOV3 and SKOV3/CDDP cells treated with combinations of CDDP, tunicamycin, and BEZ235 (blank control, CDDP, CDDP + tunicamycin, CDDP + BEZ235, and CDDP + tunicamycin + BEZ235). Increasing concentrations of tunicamycin and CDDP activated ERS in SKOV3 cells, reduced cell viability and proliferation, increased apoptosis and autophagy, enhanced expression of ERS-related proteins, and inhibited expression of PI3K/AKT/mTOR pathway-related proteins...
May 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28535855/japanese-encephalitis-virus-activates-autophagy-through-xbp1-and-atf6-er-stress-sensors-in-neuronal-cells
#8
Manish Sharma, Sankar Bhattacharyya, Kiran Bala Sharma, Shailendra Chauhan, Suramya Asthana, Malik Zainul Abdin, Sudhanshu Vrati, Manjula Kalia
Endoplasmic reticulum (ER) stress and autophagy are key cellular responses to RNA virus infection. Recent studies have shown that Japanese encephalitis virus (JEV)-induced autophagy negatively influences virus replication in mouse neuronal cells and embryonic fibroblasts, and delays virus-induced cell death. Here, we evaluated the role of ER stress pathways in inducing autophagy during JEV infection. We observed that JEV infection of neuronal cells led to activation of all three sensors of ER stress mediated by eIF2α/PERK, IRE1/XBP1 and ATF6...
May 23, 2017: Journal of General Virology
https://www.readbyqxmd.com/read/28534368/study-on-the-molecular-mechanism-of-rac3-on-regulating-autophagy-in-human-lung-cancer-cells
#9
Xuyang Xiao, Gebang Wang, Hongxu Liu
PURPOSE: Rac3 plays an important role in regulating tumorigenesis. Autophagy plays a vital role in tumorigenesis and tumor progression. The relationship between the two remains unclear. The objective of the present study was to determine the specific molecular mechanism of intracellular Rac3 in regulating autophagy and reveal the relationship between tumor cell autophagy and apoptosis. METHODS: A laser confocal microscope was used to photograph the accumulated EGFP-MAP1LC3 spots for investigating the relationship between Rac3 and autophagy at the cellular level...
March 2017: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
https://www.readbyqxmd.com/read/28522593/small-gtpase-rab1b-is-associated-with-atg9a-vesicles-and-regulates-autophagosome-formation
#10
Soichiro Kakuta, Junji Yamaguchi, Chigure Suzuki, Mitsuho Sasaki, Saiko Kazuno, Yasuo Uchiyama
ATG9 is a membrane protein that is essential for autophagy and is considered to be directly involved in the early steps of autophagosome formation. Yeast Atg9 is mainly localized to small vesicles (Atg9 vesicles), whereas mammalian ATG9A is reportedly localized to the trans-Golgi network, the endosomal compartment, and other unidentified membrane structures. To dissect the ATG9A-containing membranes, we examined the subcellular localization of ATG9A and performed immunoisolation of those membranes. ATG9A-green fluorescent protein in human culture cells was observed as numerous puncta that move rapidly throughout the cytoplasm...
May 18, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28516062/endoplasmic-reticulum-mitochondrial-ca-2-fluxes-underlying-cancer-cell-survival
#11
REVIEW
Hristina Ivanova, Martijn Kerkhofs, Rita M La Rovere, Geert Bultynck
Calcium ions (Ca(2+)) are crucial, ubiquitous, intracellular second messengers required for functional mitochondrial metabolism during uncontrolled proliferation of cancer cells. The mitochondria and the endoplasmic reticulum (ER) are connected via "mitochondria-associated ER membranes" (MAMs) where ER-mitochondria Ca(2+) transfer occurs, impacting the mitochondrial biology related to several aspects of cellular survival, autophagy, metabolism, cell death sensitivity, and metastasis, all cancer hallmarks. Cancer cells appear addicted to these constitutive ER-mitochondrial Ca(2+) fluxes for their survival, since they drive the tricarboxylic acid cycle and the production of mitochondrial substrates needed for nucleoside synthesis and proper cell cycle progression...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28504273/legionella-effector-lpg1137-shuts-down-er-mitochondria-communication-through-cleavage-of-syntaxin-17
#12
Kohei Arasaki, Yumi Mikami, Stephanie R Shames, Hiroki Inoue, Yuichi Wakana, Mitsuo Tagaya
During infection of macrophages, the pathogenic bacterium Legionella pneumophila secretes effector proteins that induce the conversion of the plasma membrane-derived vacuole into an endoplasmic reticulum (ER)-like replicative vacuole. These ER-like vacuoles are ultimately fused with the ER, where the pathogen replicates. Here we show that the L. pneumophila effector Lpg1137 is a serine protease that targets the mitochondria and their associated membranes. Lpg1137 binds to and cleaves syntaxin 17, a soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) protein that is known to participate in the regulation of mitochondrial dynamics through interaction with the mitochondrial fission factor Drp1 in fed cells and in autophagy through interaction with Atg14L and other SNAREs in starved cells...
May 15, 2017: Nature Communications
https://www.readbyqxmd.com/read/28502476/purkinje-cells-are-more-vulnerable-to-the-specific-depletion-of-cathepsin-d-than-to-that-of-atg7
#13
Masato Koike, Masahiro Shibata, Takehiko Sunabori, Junji Yamaguchi, Kenji Sakimura, Masaaki Komatsu, Keiji Tanaka, Yasuo Uchiyama
Neurologic phenotypes of cathepsin D (CTSD)-deficient mice, a murine model of neuronal ceroid lipofuscinoses, indicate the importance of CTSD for the maintenance of metabolism in central nervous system neurons. To further understand the role of CTSD in central nervous system neurons, we generated mice with a CTSD deficiency specifically in the Purkinje cells (PCs) (CTSD(Flox/Flox);GRID2-Cre) and compared their phenotypes with those of PC-selective Atg7-deficient (Atg7(Flox/Flox);GRID2-Cre) mice. In both strains of mice, PCs underwent degeneration, but the CTSD-deficient PCs disappeared more rapidly than their Atg7-deficient counterparts...
May 11, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28500249/maternal-high-fat-diet-induces-metabolic-stress-response-disorders-in-offspring-hypothalamus
#14
Long The Nguyen, Sonia Saad, Yi Tan, Carol Pollock, Hui Chen
Maternal obesity has been shown to increase the risk of obesity and related disorders in the offspring, which has been partially attributed to changes of appetite regulators in the offspring hypothalamus. On the other hand, endoplasmic reticulum (ER) stress and autophagy have been implicated in hypothalamic neuropeptide dysregulation, thus may also play important roles in such transgenerational effect.  In this study, we show that offspring born to HFD-fed dams showed significantly increased body weight and glucose intolerance, adiposity and plasma triglyceride level at weaning...
May 12, 2017: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/28498472/salinomycin-induces-endoplasmic-reticulum-stress%C3%A2-mediated-autophagy-and-apoptosis-through-generation-of-reactive-oxygen-species-in-human-glioma-u87mg-cells
#15
Sun-Nyoung Yu, Sang-Hun Kim, Kwang-Youn Kim, Jae-Hoon Ji, Young-Kyo Seo, Hak Sun Yu, Soon-Cheol Ahn
Salinomycin is a polyether ionophore antibiotic that has recently been shown to induce cell apoptosis in human cancer cells displaying multiple mechanisms of drug resistance. In the present study, we explored the impact of salinomycin on the apoptosis and autophagy as well as the correlation between those effects and endoplasmic reticulum (ER) stress molecular mechanisms in human glioma U87MG cells. Apoptosis, autophagy and reactive oxygen species (ROS) were analyzed using flow cytometry. In addition, expression levels of apoptosis-, autophagy- and ER stress-related proteins were determined by western blotting...
May 2, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28498401/luteolin-induced-apoptosis-through-activation-of-endoplasmic-reticulum-stress-sensors-in-pheochromocytoma-cells
#16
Kisang Kwon, Young-Sook Kwon, Seung-Whan Kim, Kweon Yu, Kyung-Ho Lee, O-Yu Kwon
Luteolin [2-(3,4-dihydroxyphenyl)-5,7-dihydroxy-4-chromenone] is an active flavonoid compound from Lonicera japonica (Caprifoliaceae). Luteolin inhibits tumor cell proliferation, inflammatory and oxidative stress better, when compared with other flavonoids. In the present study, it was demonstrated that luteolin induces typical apoptosis in PC12 cells (derived from a pheochromocytoma of the rat adrenal medulla) accompanied by DNA fragmentation and formation of apoptotic bodies. In addition, luteolin regulates expression of the endoplasmic reticulum (ER) chaperone binding immunoglobulin protein, activating ER stress sensors (eukaryotic initiation factor 2α phosphorylation and X‑box binding protein 1 mRNA splicing) and induced autophagy...
May 12, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28495679/autophagosome-formation-is-initiated-at-phosphatidylinositol-synthase-enriched-er-subdomains
#17
Taki Nishimura, Norito Tamura, Nozomu Kono, Yuta Shimanaka, Hiroyuki Arai, Hayashi Yamamoto, Noboru Mizushima
The autophagosome, a double-membrane structure mediating degradation of cytoplasmic materials by macroautophagy, is formed in close proximity to the endoplasmic reticulum (ER). However, how the ER membrane is involved in autophagy initiation and to which membrane structures the autophagy-initiation complex is localized have not been fully characterized. Here, we were able to biochemically analyze autophagic intermediate membranes and show that the autophagy-initiation complex containing ULK and FIP200 first associates with the ER membrane...
May 11, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28493471/what-role-does-the-stress-response-have-in-congestive-heart-failure
#18
REVIEW
Ahmed Badreddin, Youssef Fady, Hamdy Attia, Mohamed Hafez, Ahmed Khairallah, Dina Johar, Larry Bernstein
This review is concerned with cardiac malfunction as a result of an imbalance in protein proteostasis, the homeostatic balance between protein removal and regeneration in a long remodeling process involving the endoplasmic reticulum (ER) and the unfolded protein response (UPR). The importance of this is of special significance with regard to cardiac function as a high energy requiring muscular organ that has a high oxygen requirement and is highly dependent on mitochondria. The importance of mitochondria is not only concerned with high energy dependence on mitochondrial electron transport, but it also has a role in the signaling between the mitochondria and the ER under stress...
May 11, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28487545/mechanisms-of-hepatic-stellate-cell-activation
#19
REVIEW
Takuma Tsuchida, Scott L Friedman
Hepatic fibrosis is a dynamic process characterized by the net accumulation of extracellular matrix resulting from chronic liver injury of any aetiology, including viral infection, alcoholic liver disease and NASH. Activation of hepatic stellate cells (HSCs) - transdifferentiation of quiescent, vitamin-A-storing cells into proliferative, fibrogenic myofibroblasts - is now well established as a central driver of fibrosis in experimental and human liver injury. Yet, the continued discovery of novel pathways and mediators, including autophagy, endoplasmic reticulum stress, oxidative stress, retinol and cholesterol metabolism, epigenetics and receptor-mediated signals, reveals the complexity of HSC activation...
May 10, 2017: Nature Reviews. Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28482861/therapeutic-effect-of-urine-derived-stem-cells-for-protamine-lipopolysaccharide-induced-interstitial-cystitis-in-a-rat-model
#20
Jia Li, Hui Luo, Xingyou Dong, Qian Liu, Chao Wu, Teng Zhang, Xiaoyan Hu, Yuanyuan Zhang, Bo Song, Longkun Li
BACKGROUND: Interstitial cystitis (IC) is a chronic inflammation disorder mainly within the submucosal and muscular layers of the bladder. As the cause of IC remains unknown, no effective treatments are currently available. Administration of stem cell provides a potential for treatment of IC. METHODS: This study was conducted using urine-derived stem cells (USCs) for protamine/lipopolysaccharide (PS/LPS)-induced interstitial cystitis in a rodent model. In total, 60 female Sprague-Dawley rats were randomized into three experimental groups (n = 5/group): sham controls; IC model alone; and IC animals intravenously treated with USCs (1...
May 8, 2017: Stem Cell Research & Therapy
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