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endoplasmic reticulum and autophagy

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https://www.readbyqxmd.com/read/28648601/inhibition-of-pld1-activity-causes-er-stress-via-regulation-of-copii-vesicle-formation
#1
Hiroshi Nakagawa, Kazuki Hazama, Katsumasa Ishida, Masayuki Komori, Kazuhiko Nishimura, Saburou Matsuo
Phospholipase D (PLD) plays a crucial role in the regulation of some cellular processes, including autophagy and apoptosis. Accumulation of protein in the endoplasmic reticulum (ER) lumen causes ER stress. Although ER stress is a principal cause of apoptosis and autophagy, the relationship between PLD activity and ER stress remains unclear. Protein transport from the ER to the Golgi apparatus is conducted by coat complex II (COPII) transport vesicles. Here, we demonstrated that inhibition of PLD1 activity or PLD1 knockdown suppressed COPII vesicle transport in normal rat kidney (NRK) cells...
June 22, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28648145/er-membrane-protein-complex-subunit-6-emc6-is-a-novel-tumor-suppressor-in-gastric-cancer
#2
Xiaokun Wang, Yan Xia, Chentong Xu, Xin Lin, Peng Xue, Shijie Zhu, Yun Bai, Yingyu Chen
Endoplasmic reticulum (ER) membrane protein complex subunit 6 (EMC6) is a novel human autophagy-related molecule. Here, using tissue microarray and immunohistochemistry, we report that EMC6 protein is lost or reduced in glandular cells of patients with gastric adenocarcinoma, compared to normal stomach mucosa. Overexpression of EMC6 in gastric cancer cells inhibited cell growth, migration, and invasion, and induced apoptosis and cell cycle arrest at S-phase. Further investigation suggested that EMC6 overexpression in BGC823 cells reduced tumorigenicity in a xenograft model, demonstrating that EMC6 has the characteristics of a tumor suppressor...
June 26, 2017: BMB Reports
https://www.readbyqxmd.com/read/28641798/hiv-1-associated-atherosclerosis-unraveling-the-missing-link
#3
REVIEW
Alison Kearns, Jennifer Gordon, Tricia H Burdo, Xuebin Qin
Cardiovascular disease, including atherosclerosis and atherosclerosis-associated complications, is an increasing cause of morbidity and mortality in human immunodeficiency virus (HIV) patients in the post-antiretroviral therapy era. HIV alone accelerates atherosclerosis. Antiretroviral therapy; HIV-associated comorbidities, such as dyslipidemia, drug abuse, and opportunistic infections; and lifestyle are risk factors for HIV-associated atherosclerosis. However, our current understanding of HIV-associated atherogenesis is very limited and has largely been obtained from clinical observation...
June 27, 2017: Journal of the American College of Cardiology
https://www.readbyqxmd.com/read/28641278/astragaloside-iv-alleviates-heat-induced-inflammation-by-inhibiting-endoplasmic-reticulum-stress-and-autophagy
#4
Zhiwei Dong, Jian Zhou, Ying Zhang, Yajie Chen, Zichen Yang, Guangtao Huang, Yu Chen, Zhiqiang Yuan, Yizhi Peng, Tongtong Cao
BACKGROUND: Thermal injury is the main cause of pulmonary disease in stroke after burn and can be life threatening. Heat-induced inflammation is an important factor that triggers a series of induces pathological changes. However, this mechanism underlying heat-induced inflammation in thermal inhalation injury remains unclear. Studies have revealed that astragaloside-IV (AS-IV), a natural compound extracted from Astragalus membranaceus, has protective effects in inflammatory diseases. Here, we investigated whether the protective effects of AS-IV occur because of the suppression of heat-induced endoplasmic reticulum (ER) stress and excessive autophagy Methods: AS-IV was administered to Wistar rats after thermal inhalation injury and 16HBE140-cells were treated with AS-IV...
June 23, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28631572/endoplasmic-reticulum-stress-could-induce-autophagy-and-apoptosis-and-enhance-chemotherapy-sensitivity-in-human-esophageal-cancer-ec9706-cells-by-mediating-pi3k-akt-mtor-signaling-pathway
#5
Fang Zhou, Yan-Hua Li, Jian-Jun Wang, Jia Pan, Hong Lu
The study was designed to explore the mechanism of tunicamycin-induced endoplasmic reticulum stress in human esophageal cancer EC9706 cells and EC109 cells, as well as its effects on cell autophagy, apoptosis, and chemoresistance. Tunicamycin-induced endoplasmic reticulum stress model was established in EC9706 and EC109 cell lines. Western blotting was employed to detect the expression of endoplasmic reticulum stress iconic protein GRP78. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was used to evaluate the effect of different cisplatin and tunicamycin concentrations on survival rate of EC9706 cells and EC109 cells...
June 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28628644/targeting-multiple-pro-apoptotic-signaling-pathways-with-curcumin-in-prostate-cancer-cells
#6
Mariela Rivera, Yanilda Ramos, Madeline Rodríguez-Valentín, Sheila López-Acevedo, Luis A Cubano, Jin Zou, Qiang Zhang, Guangdi Wang, Nawal M Boukli
Curcumin, an extract from the turmeric rhizome (Curcuma longa), is known to exhibit anti-inflammatory, antioxidant, chemopreventive and antitumoral activities against aggressive and recurrent cancers. Accumulative data indicate that curcumin may induce cancer cell death. However, the detailed mechanism underlying its pro-apoptotic and anti-cancer effects remains to be elucidated. In the present study, we examined the signaling pathways triggered by curcumin, specifically, the exact molecular mechanisms of curcumin-induced apoptosis in highly metastatic human prostate cancer cells...
2017: PloS One
https://www.readbyqxmd.com/read/28622300/the-als-linked-e102q-mutation-in-sigma-receptor-1-leads-to-er-stress-mediated-defects-in-protein-homeostasis-and-dysregulation-of-rna-binding-proteins
#7
Alice Dreser, Jan Tilmann Vollrath, Antonio Sechi, Sonja Johann, Andreas Roos, Alfred Yamoah, Istvan Katona, Saeed Bohlega, Dominik Wiemuth, Yuemin Tian, Axel Schmidt, Jörg Vervoorts, Marc Dohmen, Cordian Beyer, Jasper Anink, Eleonora Aronica, Dirk Troost, Joachim Weis, Anand Goswami
Amyotrophic lateral sclerosis (ALS) is characterized by the selective degeneration of motor neurons (MNs) and their target muscles. Misfolded proteins which often form intracellular aggregates are a pathological hallmark of ALS. Disruption of the functional interplay between protein degradation (ubiquitin proteasome system and autophagy) and RNA-binding protein homeostasis has recently been suggested as an integrated model that merges several ALS-associated proteins into a common pathophysiological pathway...
June 16, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28622296/bcl-2-family-integrating-stress-responses-at-the-er-to-control-cell-demise
#8
REVIEW
Philippe Pihán, Amado Carreras-Sureda, Claudio Hetz
In the last decade, the endoplasmic reticulum (ER) has emerged as a central organelle regulating the core mitochondrial apoptosis pathway. At the ER membrane, a variety of stress signals are integrated toward determining cell fate, involving a complex cross talk between key homeostatic pathways including the unfolded protein response, autophagy, calcium signaling and mitochondrial bioenergetics. In this context, key regulators of cell death of the BCL-2 and TMBIM/BI-1 family of proteins have relevant functions as stress rheostats mediated by the formation of distinct protein complexes that regulate the switch between adaptive and proapoptotic phases under stress...
June 16, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28619261/sequestosome-1-sqstm1-p62-maintains-protein-folding-capacity-under-endoplasmic-reticulum-stress-in-mouse-hypothalamic-organotypic-culture
#9
Takashi Tominaga, Motomitsu Goto, Takeshi Onoue, Akira Mizoguchi, Mariko Sugiyama, Taku Tsunekawa, Daisuke Hagiwara, Yoshiaki Morishita, Yoshihiro Ito, Shintaro Iwama, Hidetaka Suga, Ryoichi Banno, Hiroshi Arima
Sequestosome 1 (SQSTM1) also known as ubiquitin-binding protein p62 (p62) is a cargo protein involved in the degradation of misfolded proteins via selective autophagy. Disruption of autophagy and resulting accumulation of misfolded proteins in the endoplasmic reticulum (ER) leads to ER stress. ER stress is implicated in several neurodegenerative diseases and obesity. As knockout of p62 (p62KO) reportedly induces obesity in mice, we examined how p62 contributes to ER stress and the ensuing unfolded protein response (UPR) in hypothalamus using mouse organotypic cultures in the present study...
June 12, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28618969/penfluridol-induces-endoplasmic-reticulum-stress-leading-to-autophagy-in-pancreatic-cancer
#10
Alok Ranjan, Nadezhda German, Constantinos Mikelis, Kalkunte Srivenugopal, Sanjay K Srivastava
Pancreatic cancer is one of the most aggressive and difficult to treat cancers. Experimental and clinical evidence suggests that high basal state autophagy in pancreatic tumors could induce resistance to chemotherapy. Recently, we have demonstrated that penfluridol suppresses pancreatic tumor growth by autophagy-mediated apoptosis both in vitro and in vivo; however, the mechanism of autophagy induction by penfluridol was not clear. Several studies have established that endoplasmic reticulum stress could lead to autophagy and inhibit tumor progression...
June 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28617241/full-length-rtn3-regulates-turnover-of-tubular-endoplasmic-reticulum-via-selective-autophagy
#11
Paolo Grumati, Giulio Morozzi, Soraya Hölper, Muriel Mari, Marie-Lena Ie Harwardt, Riqiang Yan, Stefan Müller, Fulvio Reggiori, Mike Heilemann, Ivan Dikic
The turnover of endoplasmic reticulum (ER) ensures the correct biological activity of its distinct domains. In mammalian cells the ER is degraded via a selective autophagy pathway (ER-phagy), mediated by two specific receptors: FAM134B, responsible for the turnover of ER sheets and SEC62 that regulates ER recovery following stress. Here we identified reticulon 3 (RTN3) as a specific receptor for the degradation of ER tubules. Oligomerization of the long isoform of RTN3 is sufficient to trigger fragmentation of ER tubules...
June 15, 2017: ELife
https://www.readbyqxmd.com/read/28616035/neuroprotective-effects-of-activin-a-on-endoplasmic-reticulum-stress-mediated-apoptotic-and-autophagic-pc12-cell-death
#12
Long-Xing Xue, Hong-Yu Liu, Yang Cui, Yue Dong, Jiao-Qi Wang, Qiu-Ye Ji, Jin-Ting He, Min Yao, Ying-Ying Wang, Yan-Kun Shao, Jing Mang, Zhong-Xin Xu
Activin A, a member of the transforming growth factor-beta superfamily, plays a neuroprotective role in multiple neurological diseases. Endoplasmic reticulum (ER) stress-mediated apoptotic and autophagic cell death is implicated in a wide range of diseases, including cerebral ischemia and neurodegenerative diseases. Thapsigargin was used to induce PC12 cell death, and Activin A was used for intervention. Our results showed that Activin A significantly inhibited morphological changes in thapsigargin-induced apoptotic cells, and the expression of apoptosis-associated proteins [cleaved-caspase-12, C/EBP homologous protein (CHOP) and cleaved-caspase-3] and biomarkers of autophagy (Beclin-1 and light chain 3), and downregulated the expression of thapsigargin-induced ER stress-associated proteins [inositol requiring enzyme-1 (IRE1), tumor necrosis factor receptor-associated factor 2 (TRAF2), apoptosis signal-regulating kinase 1 (ASK1), c-Jun N-terminal kinase (JNK) and p38]...
May 2017: Neural Regeneration Research
https://www.readbyqxmd.com/read/28615530/in-vivo-autophagy-and-biogenesis-of-autophagosomes-within-male-haploid-cells-during-spermiogenesis
#13
Ping Yang, Nisar Ahmed, Lingling Wang, Hong Chen, Yasir Waqas, Tengfei Liu, Abdul Haseeb, Nasrullah Bangulzai, Yufei Huang, Qiusheng Chen
Autophagy is a unique catabolic pathway that is linked to several physiological processes. However, its role in the process of spermiogenesis is largely unknown. The aim of the current study was to determine the in vivo role of autophagy and the origin of autophagosome membrane biogenesis within male haploid cells. Our immunohistochemistry results demonstrated that LC3 and ATG7 localization were increased dramatically in round to elongated spermatids (haploid cells) towards the lumen of seminiferous tubules, however, poorly expressed in the early stages of germ cells near the basal membrane...
May 26, 2017: Oncotarget
https://www.readbyqxmd.com/read/28614778/the-human-immunodeficiency-virus-hiv1-protease-inhibitor-sanquinavir-activates-autophagy-and-removes-lipids-deposited-in-lipid-droplets
#14
A Polus, M Bociaga-Jasik, U Czech, J Goralska, U Cialowicz, M Chojnacka, M Polus, K Jurowski, A Dembinska-Kiec
Reduction in mortality and increased average life span of the human immunodeficiency virus (HIV)-infected patients treated with antiretroviral therapy (ART) are associated with the risk of unwanted effects, such as insulin resistance and dyslipidemia with cardiovascular complications. Antiretroviral therapy may also be associated with lipodystrophy characterized as peripheral lipoatrophy with central fat accumulation. Understanding the molecular mechanisms of lipodystrophy caused by ART is important for therapeutic strategy and the prediction of side-effects...
April 2017: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
https://www.readbyqxmd.com/read/28605878/an-oasis-in-the-desert-of-cancer-chemotherapeutic-resistance-the-enlightenment-from-reciprocal-crosstalk-between-signaling-pathways-of-upr-and-autophagy-in-cancers
#15
REVIEW
Yuhang Zhang, Xianjun Qu, Lingfan Jiang
Endoplasmic reticulum (ER), principal but complex, functions as the pleiotropic organelle for proper protein folding, Ca(2+) storage as well as lipid and carbohydrate metabolisms. Diverse microenviromental insults including, but not limited to, inflammatory reaction, glucose imbalance and hypoxia, elicit the accumulation of potentially toxic unfolded proteins in the ER lumen. Under the condition of these cellular threats, the autophagy with the well-orchestrated program containing over 30 autophagy-related genes (ATGs) might be initiated for degrading and recycling of the cumulative misfolded proteins and other related abnormal cytoplasmic components...
August 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28601430/imiquimod-induced-autophagy-is-regulated-by-er-stress-mediated-pkr-activation-in-cancer-cells
#16
Shu-Hao Chang, Shi-Wei Huang, Sin-Ting Wang, Kai-Cheng Chung, Chia-Wei Hsieh, Jun-Kai Kao, Yi-Ju Chen, Chun-Ying Wu, Jeng-Jer Shieh
BACKGROUND: Autophagy is a highly conserved cellular catabolic pathway for degradation and recycling of intracellular components in response to nutrient starvation or environmental stress. Endoplasmic reticulum (ER) homeostasis can be disturbed by physiological and pathological influences, resulting in accumulation of misfolded and unfolded proteins in the ER lumen, a condition referred to as ER stress. Imiquimod (IMQ), a Toll-like receptor (TLR) 7 ligand, possesses anti-tumor and anti-viral activities in vitro and in vivo...
May 2, 2017: Journal of Dermatological Science
https://www.readbyqxmd.com/read/28598856/glucocerebrosidase-mutations-in-parkinson-disease
#17
Grace O'Regan, Ruth-Mary deSouza, Roberta Balestrino, A H Schapira
Following the discovery of a higher than expected incidence of Parkinson Disease (PD) in Gaucher disease, a lysosomal storage disorder, mutations in the glucocerebrocidase (GBA) gene, which encodes a lysosomal enzyme involved in sphingolipid degradation were explored in the context of idiopathic PD. GBA mutations are now known to be the single largest risk factor for development of idiopathic PD. Clinically, on imaging and pharmacologically, GBA PD is almost identical to idiopathic PD. In patients with a known GBA mutation, it is possible to monitor for prodromal signs of PD...
June 7, 2017: Journal of Parkinson's Disease
https://www.readbyqxmd.com/read/28598844/combustion-derived-nanoparticles-in-key-brain-target-cells-and-organelles-in-young-urbanites-culprit-hidden-in-plain-sight-in-alzheimer-s-disease-development
#18
Angélica González-Maciel, Rafael Reynoso-Robles, Ricardo Torres-Jardón, Partha S Mukherjee, Lilian Calderón-Garcidueñas
Millions of children and young adults are exposed to fine particulate matter (PM2.5) and ozone, associated with Alzheimer's disease (AD) risk. Mexico City (MC) children exhibit systemic and brain inflammation, low cerebrospinal fluid (CSF) Aβ1-42, breakdown of nasal, olfactory, alveolar-capillary, duodenal, and blood-brain barriers, volumetric and metabolic brain changes, attention and short-term memory deficits, and hallmarks of AD and Parkinson's disease. Airborne iron-rich strongly magnetic combustion-derived nanoparticles (CDNPs) are present in young urbanites' brains...
June 3, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28593135/evaluation-of-cell-death-pathways-initiated-by-antitumor-drugs-melatonin-and-valproic-acid-in-bladder-cancer-cells
#19
Siwei Liu, Bilin Liang, Huiting Jia, Yuhan Jiao, Zhongqiu Pang, Yongye Huang
Effective drug combinations have the potential to strengthen therapeutic efficacy and combat drug resistance. Both melatonin and valproic acid (VPA) exhibit antitumor activities in various cancer cells. The aim of this study was to evaluate the cell death pathways initiated by anticancer combinatorial effects of melatonin and VPA in bladder cancer cells. The results demonstrated that the combination of melatonin and VPA leads to significant synergistic growth inhibition of UC3 bladder cancer cells. Gene expression studies revealed that cotreatment with melatonin and VPA triggered the up-regulation of certain genes related to apoptosis (TNFRSF10A and TNFRSF10B), autophagy (BECN, ATG3 and ATG5) and necrosis (MLKL, PARP-1 and RIPK1)...
June 2017: FEBS Open Bio
https://www.readbyqxmd.com/read/28585211/non-alcoholic-fatty-liver-disease
#20
Atilla Engin
Non-alcoholic fatty liver disease (NAFLD) is in parallel with the obesity epidemic and it is the most common cause of liver diseases. The development of hepatic steatosis in majority of patients is linked to dietary fat ingestion. NAFLD is characterized by excess accumulation of triglyceride in the hepatocyte due to both increased inflow of free fatty acids and de novo hepatic lipogenesis. Insulin resistance with the deficiency of insulin receptor substrate-2 (IRS-2)-associated phosphatidylinositol 3-kinase (PI3K) activity causes an increase in intracellular fatty acid-derived metabolites such as diacylglycerol, fatty acyl CoA or ceramides...
2017: Advances in Experimental Medicine and Biology
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