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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
Emily C Lumley, Acadia R Osborn, Jessica E Scott, Amanda G Scholl, Vicki Mercado, Young T McMahan, Zachary G Coffman, Jay L Brewster
The endoplasmic reticulum (ER) has the ability to signal organelle dysfunction via a complex signaling network known as the unfolded protein response (UPR). In this work, hamster fibroblast cells exhibiting moderate levels of ER stress were compared to those exhibiting severe ER stress. Inhibition of N-linked glycosylation was accomplished via a temperature-sensitive mutation in the Dad1 subunit of the oligosaccharyltransferase (OST) complex or by direct inhibition with tunicamycin (Tm). Temperature shift (TS) treatment generated weak activation of ER stress signaling when compared to doses of Tm that are typically used in ER stress studies (500-1000 nM)...
October 20, 2016: Cell Stress & Chaperones
Sounik Saha, Xunhao Xiong, Prabir K Chakraborty, Khader Shameer, Rochelle R Arvizo, Rachel A Kudgus, Shailendra Kumar Dhar Dwivedi, Md Nazir Hossen, Elizabeth M Gillies, J David Robertson, Joel T Dudley, Raul A Urrutia, Russell G Postier, Resham Bhattacharya, Priyabrata Mukherjee
Altered tumor microenvironment (TME) arising from a bidirectional crosstalk between the pancreatic cancer cells (PCCs) and the pancreatic stellate cells (PSCs) is implicated in the dismal prognosis in pancreatic ductal adenocarcinoma (PDAC), yet effective strategies to disrupt the crosstalk is lacking. Here, we demonstrate that gold nanoparticles (AuNPs) inhibit proliferation and migration of both PCCs and PSCs by disrupting the bidirectional communication via alteration of the cell secretome. Analyzing the key proteins identified from a functional network of AuNP-altered secretome in PCCs and PSCs, we demonstrate that AuNPs impair secretions of major hub node proteins in both cell types and transform activated PSCs toward a lipid-rich quiescent phenotype...
October 19, 2016: ACS Nano
Zhe Meng, Cristina Ruberti, Zhizhong Gong, Federica Brandizzi
Completion of a plant's life cycle depends on successful prioritization of signaling favoring either growth or defense. Although hormones are pivotal regulators of growth-defense tradeoffs, the underlying signaling mechanisms remain obscure. The unfolded protein response (UPR) is essential for physiological growth as well as endoplasmic reticulum (ER)-stress management in unfavorable growth conditions. The plant UPR transducers are the kinase and ribonuclease IRE1 and the transcription factors bZIP28 and bZIP60...
October 16, 2016: Plant Journal: for Cell and Molecular Biology
Soshi Kanemoto, Ryota Nitani, Tatsuhiko Murakami, Masayuki Kaneko, Rie Asada, Koji Matsuhisa, Atsushi Saito, Kazunori Imaizumi
The endoplasmic reticulum (ER) plays a pivotal role in maintaining cellular homeostasis. However, numerous environmental and genetic factors give rise to ER stress by inducing an accumulation of unfolded proteins. Under ER stress conditions, cells initiate the unfolded protein response (UPR). Here, we demonstrate a novel aspect of the UPR by electron microscopy and immunostaining analyses, whereby multivesicular body (MVB) formation was enhanced after ER stress. This MVB formation was influenced by inhibition of ER stress transducers inositol required enzyme 1 (IRE1) and PKR-like ER kinase (PERK)...
October 7, 2016: Biochemical and Biophysical Research Communications
Imran Khan, Souren Paul, Rekha Jakhar, Monika Bhardwaj, Jaehong Han, Sun Chul Kang
Although quercetin is very well known for its anticancer activity, however it shows some drawbacks. Herein, we have evaluated the apoptotic effect TEF (5, 3'-dihydroxy-3, 7, 4'-triethoxyflavone), a newly synthesized quercetin derivative on HCT-116 colon cancer cells. After 24h of treatment, the proliferation of colon cancer cells was inhibited by TEF. TEF induced apoptosis, as confirmed by the presence of fragmented nuclei, reduced mitochondrial membrane potential, and elevated cytoplasmic and mitochondrial reactive oxygen species (ROS) levels...
October 6, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Junnan Liu, Maolin Xiao, Jianjun Li, Delin Wang, Yunfeng He, Jiang He, Fei Gao, Li Mai, Ying Li, Yong Liang, Yuejiang Liu, Xiaoni Zhong
BACKGROUND: Currently, the role of UPR signaling in prostate cancer (PCa) is unclear. To evaluate the relationship between UPR signaling pathway and the prognosis of PCa, we explored the expression of IRE1, PERK, and ATF6 in tissues. METHODS: A total of 160 PCa and 30 benign prostate hyperplasia (BPH) tissues were collected. The expression of UPR signaling factors was assessed by immunohistochemistry. The staining characteristics were identified and evaluated for associations with clinicopathologic parameters, PSA recurrence survival, and prostate cancer-specific morality...
October 8, 2016: Prostate
Sarinthorn Thummayot, Chainarong Tocharus, Apichart Suksamrarn, Jiraporn Tocharus
This study evaluated the mechanisms underlying the protective effect of cyanidin against Aβ25-35-induced neuronal cell death in SK-N-SH cells. Aβ25-35-induced neurotoxicity is characterized by a decrease in cell viability, inducing the expression of endoplasmic reticulum (ER) stress proteins; an increase in intracellular reactive oxygen species (ROS) production; and an increase in intracellular calcium release. Aβ25-35 also induces neuronal toxicity through the disturbance of ER calcium levels. Pretreatment with cyanidin significantly attenuated the Aβ25-35-induced loss of cell viability, reducing the expression of endoplasmic reticulum (ER) stress response proteins with regard to the down-regulation of the expression levels of 78 kDa glucose regulated protein (Grp78), phosphorylated forms of pancreatic ER elF2α kinase (PERK), eukaryotic initiation factor 2 α (eIF2α), and inositol-requiring enzyme 1 (IRE1), and the expression levels of X-box binding protein 1 (XBP-1), activating transcription factor 6 (ATF6), and CCAAT/enhancer binding protein homologous transcription factor (C/EBP) homologous protein (CHOP); decreased intracellular ROS production; decreased intracellular calcium release; and reduced down-regulation of the protein expression levels of calpain and cleaved caspase-12...
September 30, 2016: Neurochemistry International
Jianqiong Yang, Haiqing Liu, Linfu Li, Hai Liu, Weimei Shi, Xiaoliang Yuan, Longhuo Wu
IRE1 signaling is the most evolutionarily conserved branch in the UPR. IRE1 is an ER stress sensor and provides a structure-based platform for the unfolded proteins docking, which causes the luminal domain conformational change and oligomerization. This self-association of IRE1 facilitates the phosphorylation of activation loop, which unlocks the auto-inhibition in the kinase domain. The activating mechanistic cascade is thus initiated to induce DFG-in conformational change and movement of αC-helix to the active site...
September 27, 2016: Current Medicinal Chemistry
José Carlos Páez-Franco, Ignacio González-Sánchez, Nora A Gutiérrez-Nájera, Lilián G Valencia-Turcotte, Alfonso Lira-Rocha, Marco A Cerbón, Rogelio Rodríguez-Sotres
9-[(3-chloro)phenylamine]-2-[3-(diethylamine)propylamine]thiazolo[5,4-b]quinolone (D3ClP) is a bioisostere of N-(4-(acridin-9-ylamino)-3-methoxyphenyl)methanesulfonamide (m-AMSA) a DNA topoisomerase II inhibitor with proven cytotoxic activity and known to induce DNA damage and apoptotic cell death in K562 cells. However, recent evidence is not consistent with DNA topoisomerase II (DNA TOP2) as the primary target of D3ClP, in contrast to m-AMSA. We provide evidence of histone γH2AX phosphorylation at Ser135 in HeLa cells treated with D3ClP, a marker of DNA double strand repair through Mre11-Rad50-Nbs1 (MRN) pathway...
September 29, 2016: Journal of Cellular Biochemistry
Juan Chen, Xue-Feng Hou, Gang Wang, Qing-Xiang Zhong, Ying Liu, Hui-Hui Qiu, Nan Yang, Jun-Fei Gu, Chun-Fei Wang, Li Zhang, Jie Song, Lu-Qi Huang, Xiao-Bin Jia, Ming-Hua Zhang, Liang Feng
ETHNOPHARMACOLOGICAL RELEVANCE: Multiple lines of evidences have suggested that endoplasmic reticulum (ER) stress-related inflammatory responses play a critical role in the pathogenesis of diabetic nephropathy (DN). Moutan Cortex (MC), the root bark of Paeonia suffruticosa Andr., is a well-known traditional Chinese medicine (TCM), which has been used clinically for treating inflammatory diseases in China. The findings from our previous research suggested that terpene glycoside (TG) component of MC possessed favorable anti-inflammatory properties in curing DN...
September 21, 2016: Journal of Ethnopharmacology
Ha Ram Bae, Dae Hyun Kim, Min Hi Park, Bonggi Lee, Min Jo Kim, Eun Kyeong Lee, Ki Wung Chung, Seong Min Kim, Dong Soon Im, Hae Young Chung
β-Hydroxybutyrate, a ketone body that is used as an energy source in organs such as the brain, muscle, and heart when blood glucose is low, is produced by fatty acid oxidation in the liver under the fasting state. Endoplasmic reticulum (ER) stress is linked with the generation of intracellular reactive oxygen species and the accumulation of misfolded protein in the ER. ER stress is known to induce the NOD-like receptor protein 3 inflammasome, which mediates activation of the proinflammatory cytokine interleukin-1β, whose maturation is caspase-1-dependent...
September 19, 2016: Oncotarget
Hang Nguyen, Bruce D Uhal
Recent work from this laboratory showed that endoplasmic reticulum (ER) stress-induced apoptosis of alveolar epithelial cells (AECs) is regulated by the autocrine angiotensin (ANG)II/ANG1-7 system. The proteasome inhibitor MG132 or surfactant protein C (SP-C) BRICHOS domain mutation G100S induced apoptosis in human AECs by activating the pro-apoptotic cathepsin D and reducing anti-apoptotic angiotensin converting enzyme-2 (ACE-2). This study tested the hypothesis that ER stress-induced apoptosis of human AECs might be mediated by influence of the unfolded protein response (UPR) on the autocrine ANGII/ANG1-7 system...
September 16, 2016: American Journal of Physiology. Lung Cellular and Molecular Physiology
Matthias Kroiss, Silviu Sbiera, Sabine Kendl, Max Kurlbaum, Martin Fassnacht
Mitotane is the only drug approved for treatment of the orphan disease adrenocortical carcinoma (ACC) and was recently shown to be the first clinically used drug acting through endoplasmic reticulum (ER)-stress induced by toxic lipids. Since mitotane has limited clinical activity as monotherapy, we here study the potential of activating ER-stress through alternative pathways. The single reliable NCI-H295 cell culture model for ACC was used to study the impact MG132, bortezomib (BTZ) and carfilzomib (CFZ) on mRNA and protein expression of ER-stress markers, cell viability and steroid hormone secretion...
September 8, 2016: Hormones & Cancer
Kwang-Woo Jung, Yee-Seul So, Yong-Sun Bahn
Cryptococcus neoformans, a global fungal meningitis pathogen, employs the unfolded protein response pathway. This pathway, which consists of an evolutionarily conserved Ire1 kinase/endoribonuclease and a unique transcription factor (Hxl1), modulates the endoplasmic reticulum stress response and pathogenicity. Here, we report that the unfolded protein response pathway governs sexual and unisexual differentiation of C. neoformans in an Ire1-dependent but Hxl1-independent manner. The ire1∆ mutants showed defects in sexual mating, with reduced cell fusion and pheromone-mediated formation of the conjugation tube...
2016: Scientific Reports
Sarah E Kobylewski, Kimberly A Henderson, Kristin E Yamada, Curtis D Eckhert
Fruits, nuts, legumes, and vegetables are rich sources of boron (B), an essential plant nutrient with chemopreventive properties. Blood boric acid (BA) levels reflect recent B intake, and men at the US mean intake have a reported non-fasting level of 10 μM. Treatment of DU-145 prostate cancer cells with physiological concentrations of BA inhibits cell proliferation without causing apoptosis and activates eukaryotic initiation factor 2 (eIF2α). EIF2α induces cell differentiation and protects cells by redirecting gene expression to manage endoplasmic reticulum stress...
September 1, 2016: Biological Trace Element Research
Omar Paul Arias Gaguancela, Lizbeth Peña Zúñiga, Alexis Vela Arias, Dennis Halterman, Francisco Javier Flores, Ida Elisabeth Johansen, Aiming Wang, Yasuyuki Yamaji, Jeanmarie Verchot-Lubicz
The inositol requiring enzyme (IRE1) is an endoplasmic reticulum (ER) stress sensor. When activated, it splices the bZIP60 mRNA producing a truncated transcription factor that upregulates genes involved in the unfolded protein response (UPR). Bax inhibitor 1 (BI-1) is another ER stress sensor that regulates cell death in response to environmental assaults. The potyvirus 6K2 and potexvirus TGB3 proteins are known to reside in the ER, serving respectively as anchors for the viral replicase and movement protein complex...
August 31, 2016: Molecular Plant-microbe Interactions: MPMI
Madduma Hewage Susara Ruwan Kumara, Mei Jing Piao, Kyoung Ah Kang, Yea Seong Ryu, Jeong Eon Park, Kristina Shilnikova, Jin Oh Jo, Young Sun Mok, Jennifer H Shin, Yeonsoo Park, Seong Bong Kim, Suk Jae Yoo, Jin Won Hyun
Colorectal cancer is a common type of tumor among both men and women worldwide. Conventional remedies such as chemotherapies pose the risk of side‑effects, and in many cases cancer cells develop chemoresistance to these treatments. Non‑thermal gas plasma (NTGP) was recently identified as a potential tool for cancer treatment. In this study, we investigated the potential use of NTGP to control SNUC5 human colon carcinoma cells. We hypothesized that NTGP would generate reactive oxygen species (ROS) in these cells, resulting in induction of endoplasmic reticulum (ER) stress...
October 2016: Oncology Reports
Liwei He, Xianbang Hou, Fangtian Fan, Hongyan Wu
CONTEXT: Activation of hepatic stellate cells (HSCs) is a hallmark of liver fibrosis. Quercetin has benefits for liver fibrosis, but the mechanisms are unknown. OBJECTIVE: We investigated the quercetin effect on HSC survival and the role of endoplasmic reticulum stress (ERS). MATERIALS AND METHODS: Rat HSCs and LO2 hepatocytes were treated with quercetin (0.5-120 μM) for 24 h. Quercetin (10-40 μM) effects on apoptosis for 24 h were analyzed by flow cytometry and TUNEL staining...
August 30, 2016: Pharmaceutical Biology
Wen-Yue Xie, Xiang-Dong Zhou, Juan Yang, Ling-Xiu Chen, Dan-Hua Ran
The occurrence and mechanisms of autophagy induced by heat stress are not well known in lung cancer cells. Here, we have demonstrated that heat stress induces autophagy in A549 and NCI-H460 cells through morphological and biochemical analyses. The inhibition of autophagy by chloroquine, 3-methyladenine and Beclin 1 siRNA enhanced heat-induced apoptosis. Moreover, the combination of chloroquine and heat stress inhibited tumor growth and enhanced apoptosis in vivo experiments. In addition, heat-induced autophagy involved the ER stress pathway (PERK- or IRE1-dependent)...
October 1, 2016: Archives of Biochemistry and Biophysics
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