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knock down of GRP78

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https://www.readbyqxmd.com/read/27913816/genetic-ablation-or-pharmacologic-inhibition-of-autophagy-mitigated-nsaid-associated-gastric-damages
#1
Chan Young Ock, Jong-Min Park, Young-Min Han, Migyeong Jeong, Mi-Young Kim, Ho Jae Lee, Ki Baik Hahm
: Non-steroidal anti-inflammatory drug (NSAID)-associated endoplasmic reticulum (ER) stress (a cyclooxygenase-2-independent mechanism) and consequent autophagic cell death are responsible for NSAID-associated gastric damage. Therefore, alleviating cytotoxicity executed via ER stress and autophagy can be a strategy to prevent NSAID-associated gastric damage. Here, we explored whether genetic or pharmacologic inhibition of autophagy can mitigate NSAID-associated gastric damage in in vitro and in vivo models...
December 2, 2016: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/27903966/pde5-inhibitors-enhance-the-lethality-of-pemetrexed-through-inhibition-of-multiple-chaperone-proteins-and-via-the-actions-of-cyclic-gmp-and-nitric-oxide
#2
Laurence Booth, Jane L Roberts, Andrew Poklepovic, Sarah Gordon, Paul Dent
Phosphodiesterase 5 (PDE5) inhibitors prevent the breakdown of cGMP that results in prolonged protein kinase G activation and the generation of nitric oxide. PDE5 inhibitors enhanced the anti-NSCLC cell effects of the NSCLC therapeutic pemetrexed. [Pemetrexed + sildenafil] activated an eIF2α - ATF4 - CHOP - Beclin1 pathway causing formation of toxic autophagosomes; activated a protective IRE1 - XBP-1 - chaperone induction pathway; and activated a toxic eIF2α - CHOP - DR4 / DR5 / CD95 induction pathway. [Pemetrexed + sildenafil] reduced the expression of c-FLIP-s, MCL-1 and BCL-XL that was blocked in a cell-type -dependent fashion by either over-expression of HSP90 / GRP78 / HSP70 / HSP27 or by blockade of eIF2α-CHOP signaling...
November 26, 2016: Oncotarget
https://www.readbyqxmd.com/read/27677243/insulin-enhanced-leptin-induced-stat3-signaling-by-inducing-grp78
#3
Mina Thon, Toru Hosoi, Koichiro Ozawa
Leptin, an adipocyte-derived hormone, centrally regulates energy homeostasis. Overlaps in the regulation of glucose and energy homeostasis have been reported between leptin and insulin. However, the effects of insulin on leptin's actions in the central nervous system (CNS) have not yet been elucidated in detail. In the present study, we found that insulin potentiated leptin's actions through GRP78 in the neuronal cell line, SH-SY5Y-ObRb. Since insulin induces GRP78, we speculated that it may also enhance leptin's actions through this induction...
September 28, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27404504/angiotensin-ii-receptor-one-at1-mediates-dextrose-induced-endoplasmic-reticulum-stress-and-superoxide-production-in-human-coronary-artery-endothelial-cells
#4
Michael J Haas, Luisa Onstead-Haas, Tracey Lee, Maisoon Torfah, Arshag D Mooradian
BACKGROUND: Renin-angiotensin-aldosterone system (RAAS) has been implicated in diabetes-related vascular complications partly through oxidative stress. OBJECTIVE: To determine the role of angiotensin II receptor subtype one (AT1) in dextrose induced endoplasmic reticulum (ER) stress, another cellular stress implicated in vascular disease. METHODS: Human coronary artery endothelial cells with or without AT1 receptor knock down were treated with 27...
October 1, 2016: International Journal of Cardiology
https://www.readbyqxmd.com/read/27379204/rationally-repurposing-ruxolitinib-jakafi-%C3%A2-as-a-solid-tumor-therapeutic
#5
Mehrad Tavallai, Laurence Booth, Jane L Roberts, Andrew Poklepovic, Paul Dent
We determined whether the approved myelofibrosis drug ruxolitinib (Jakafi(®)), an inhibitor of Janus kinases 1/2 (JAK1 and JAK2), could be repurposed as an anti-cancer agent for solid tumors. Ruxolitinib synergistically interacted with dual ERBB1/2/4 inhibitors to kill breast as well as lung, ovarian and brain cancer cells. Knock down of JAK1/2 or of ERBB1/2/3/4 recapitulated on-target drug effects. The combination of (ruxolitinib + ERBB1/2/4 inhibitor) rapidly inactivated AKT, mTORC1, mTORC2, STAT3, and STAT5, and activated eIF2α...
2016: Frontiers in Oncology
https://www.readbyqxmd.com/read/27293989/recombinant-newcastle-disease-virus-rl-rvg-triggers-autophagy-and-apoptosis-in-gastric-carcinoma-cells-by-inducing-er-stress
#6
Xuefeng Bu, Yinghai Zhao, Zhijian Zhang, Mubin Wang, Mi Li, Yulan Yan
We have reported that the recombinant avirulent Newcastle disease virus (NDV) LaSota strain expressing the rabies virus glycoprotein (rL-RVG) could induce autophagy and apoptosis in gastric carcinoma cells. In the present study, we explored the upstream regulators, endoplasmic reticulum (ER) stress that induce autophagy and apoptosis and the relationships among them. For this purpose, SGC-7901 and HGC cells were infected with rL-RVG. NDV LaSota strain and phosphate-buffered saline (PBS) were treated as the control groups...
2016: American Journal of Cancer Research
https://www.readbyqxmd.com/read/27259258/multi-kinase-inhibitors-interact-with-sildenafil-and-erbb1-2-4-inhibitors-to-kill-tumor-cells-in-vitro-and-in-vivo
#7
Laurence Booth, Thomas Albers, Jane L Roberts, Mehrad Tavallai, Andrew Poklepovic, Iryna O Lebedyeva, Paul Dent
We have recently demonstrated that multi-kinase inhibitors such as sorafenib and pazopanib can suppress the detection of chaperones by in situ immuno-fluorescence, which is further enhanced by phosphodiesterase 5 inhibitors. Sorafenib and pazopanib inhibited the HSP90 ATPase activity with IC50 values of ~1.0 μM and ~75 nM, respectively. Pazopanib docked in silico with two possible poses into the HSP90 ATP binding pocket. Pazopanib and sildenafil combined to reduce the total protein levels of HSP1H/p105 and c-MYC and to reduce their co-localization...
May 31, 2016: Oncotarget
https://www.readbyqxmd.com/read/27256049/-roles-of-glucose-regulated-protein-78-in-proliferation-and-migration-of-human-colorectal-carcinoma-cell-line-rko
#8
Q X Ji, L L Liu, L Li, X M Xing
OBJECTIVE: To investigate the roles of glucose regulated protein 78(GRP78) in proliferation and migration of human colorectal carcinoma cell RKO. METHODS: The colorectal carcinoma cell line RKO was transfected by lentiviral vector pLV-shRNA GRP78 and lentivirus vector pLV-control. MTT test and colony formation assay were used to evaluate the cell proliferation ability. Distribution of cell cycle was analyzed by flow cytometry. Cell migration ability was detected by scratches migration experiment...
June 8, 2016: Zhonghua Bing Li Xue za Zhi Chinese Journal of Pathology
https://www.readbyqxmd.com/read/27187154/ar-12-inhibits-multiple-chaperones-concomitant-with-stimulating-autophagosome-formation-collectively-preventing-virus-replication
#9
Laurence Booth, Jane L Roberts, Heath Ecroyd, Sarah R Tritsch, Sina Bavari, St Patrick Reid, Stefan Proniuk, Alexander Zukiwski, Abraham Jacob, Claudia S Sepúlveda, Federico Giovannoni, Cybele C García, Elsa Damonte, Javier González-Gallego, María J Tuñón, Paul Dent
We have recently demonstrated that AR-12 (OSU-03012) reduces the function and ATPase activities of multiple HSP90 and HSP70 family chaperones. Combined knock down of chaperones or AR-12 treatment acted to reduce the expression of virus receptors and essential glucosidase proteins. Combined knock down of chaperones or AR-12 treatment inactivated mTOR and elevated ATG13 S318 phosphorylation concomitant with inducing an endoplasmic reticulum stress response that in an eIF2α-dependent fashion increased Beclin1 and LC3 expression and autophagosome formation...
October 2016: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/27182794/abrus-agglutinin-a-type-ii-ribosome-inactivating-protein-inhibits-akt-ph-domain-to-induce-endoplasmic-reticulum-stress-mediated-autophagy-dependent-cell-death
#10
Prashanta Kumar Panda, Birendra Behera, Biswa Ranjan Meher, Durgesh Nandini Das, Subhadip Mukhopadhyay, Niharika Sinha, Prajna Paramita Naik, Bibhas Roy, Joyjyoti Das, Subhankar Paul, Tapas K Maiti, Rajesh Agarwal, Sujit K Bhutia
Abrus agglutinin (AGG), a type II ribosome-inactivating protein has been found to induce mitochondrial apoptosis. In the present study, we documented that AGG-mediated Akt dephosphorylation led to ER stress resulting the induction of autophagy-dependent cell death through the canonical pathway in cervical cancer cells. Inhibition of autophagic death with 3-methyladenosine (3-MA) and siRNA of Beclin-1 and ATG5 increased AGG-induced apoptosis. Further, inhibiting apoptosis by Z-DEVD-FMK and N-acetyl cysteine (NAC) increased autophagic cell death after AGG treatment, suggesting that AGG simultaneously induced autophagic and apoptotic death in HeLa cells...
May 16, 2016: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/27061377/e-platinum-a-newly-synthesized-platinum-compound-induces-apoptosis-through-ros-triggered-er-stress-in-gastric-carcinoma-cells
#11
Xiaoping Wang, Qinglong Guo, Lei Tao, Li Zhao, Yan Chen, Teng An, Zhen Chen, Rong Fu
Gastric cancer (GC) is still one of the leading causes of death in cancer-related diseases. In this study, we aimed to investigate the antitumor effect of E Platinum, a newly platinum-based chemotherapeutic agent bearing the basic structure of Oxaliplatin, in a variety of gastric carcinoma cells and the underlying mechanisms. We demonstrated that E Platinum significantly induced apoptosis in gastric cancer cells via mitochondrial apoptotic pathway as a result of increased reactive oxygen species (ROS). We also found that E Platinum enhanced Ca(2+) flux out from the endoplasmic reticulum by increasing the protein expression of IP3R type 1 (IP3R1) and decreasing the expression of ERp44...
January 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/26861384/a-kdel-retrieval-system-for-er-golgi-transport-of-japanese-encephalitis-viral-particles
#12
Robert Y L Wang, Yu-Jen Wu, Han-Shan Chen, Chih-Jung Chen
Evidence has emerged that RNA viruses utilize the host secretory pathway for processing and trafficking mature viral particles and for exiting the infected cells. Upon completing the complex assembly process, the viral particles take advantage of the cellular secretory trafficking machinery for their intracellular trafficking toward the Golgi organelle and budding or export of virions. In this study, we showed that Japanese encephalitis virus (JEV)-induced extracellular GRP78 contains no KDEL motif using an anti-KDEL-specific antibody...
February 2016: Viruses
https://www.readbyqxmd.com/read/26559141/acid-induced-autophagy-protects-human-lung-cancer-cells-from-apoptosis-by-activating-er-stress
#13
Wen-Yue Xie, Xiang-Dong Zhou, Qi Li, Ling-Xiu Chen, Dan-Hua Ran
An acidic tumor microenvironment exists widely in solid tumors. However, the detailed mechanism of cell survival under acidic stress remains unclear. The aim of this study is to clarify whether acid-induced autophagy exists and to determine the function and mechanism of autophagy in lung cancer cells. We have found that acute low pH stimulated autophagy by increasing LC3-positive punctate vesicles, increasing LC3 II expression levels and reducing p62 protein levels. Additionally, autophagy was inhibited by the addition of Baf or knockdown of Beclin 1, and cell apoptosis was increased markedly...
December 10, 2015: Experimental Cell Research
https://www.readbyqxmd.com/read/26481188/blocking-autophagy-enhances-meloxicam-lethality-to-hepatocellular-carcinoma-by-promotion-of-endoplasmic-reticulum-stress
#14
Jingtao Zhong, Xiaofeng Dong, Peng Xiu, Fuhai Wang, Ju Liu, Honglong Wei, Zongzhen Xu, Feng Liu, Tao Li, Jie Li
OBJECTIVES: Meloxicam, a selective cyclooxygenase-2 (COX-2) inhibitor, has been demonstrated to exert anti-tumour effects against various malignancies. However, up to now, mechanisms involved in meloxicam anti-hepatocellular carcinoma effects have remained unclear. MATERIALS AND METHODS: Cell viability and apoptosis were assessed by CCK-8 and flow cytometry. Endoplasmic reticulum (ER) stress and autophagy-associated molecules were analysed by western blotting and immunofluorescence assay...
December 2015: Cell Proliferation
https://www.readbyqxmd.com/read/26307968/endoplasmic-reticulum-stress-cooperates-in-zearalenone-induced-cell-death-of-raw-264-7-macrophages
#15
Fenglei Chen, Qian Li, Zhe Zhang, Pengfei Lin, Lanjie Lei, Aihua Wang, Yaping Jin
Zearalenone (ZEA) is a fungal mycotoxin that causes cell apoptosis and necrosis. However, little is known about the molecular mechanisms of ZEA toxicity. The objective of this study was to explore the effects of ZEA on the proliferation and apoptosis of RAW 264.7 macrophages and to uncover the signaling pathway underlying the cytotoxicity of ZEA in RAW 264.7 macrophages. This study demonstrates that the endoplasmic reticulum (ER) stress pathway cooperated in ZEA-induced cell death of the RAW 264.7 macrophages...
2015: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/25923692/high-density-lipoprotein-prevents-endoplasmic-reticulum-stress-induced-downregulation-of-liver-lox-1-expression
#16
Dan Hong, Ling-Fang Li, Hai-Chao Gao, Xiang Wang, Chuan-Chang Li, Ying Luo, Yong-Ping Bai, Guo-Gang Zhang
Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is a specific cell-surface receptor for oxidized-low-density lipoprotein (ox-LDL). The impact of high-density lipoprotein (HDL) on endoplasmic reticulum (ER) stress-mediated alteration of the LOX-1 level in hepatocytes remains unclear. We aimed to investigate the impact on LOX-1 expression by tunicamycin (TM)-induced ER stress and to determine the effect of HDL on TM-affected LOX-1 expression in hepatic L02 cells. Overexpression or silencing of related cellular genes was conducted in TM-treated cells...
2015: PloS One
https://www.readbyqxmd.com/read/25788268/piperlongumine-selectively-kills-hepatocellular-carcinoma-cells-and-preferentially-inhibits-their-invasion-via-ros-er-mapks-chop
#17
Yong Chen, Ju Mei Liu, Xin Xin Xiong, Xin Yao Qiu, Feng Pan, Di Liu, Shu Jue Lan, Si Jin, Shang Bin Yu, Xiao Qian Chen
Hepatocellular carcinomas (HCC) are highly malignant and aggressive tumors lack of effective therapeutic drugs. Piperlongumine (PL), a natural product isolated from longer pepper plants, is recently identified as a potent cytotoxic compound highly selective to cancer cells. Here, we reported that PL specifically suppressed HCC cell migration/invasion via endoplasmic reticulum (ER)-MAPKs-CHOP signaling pathway. PL selectively killed HCC cells but not normal hepatocytes with an IC50 of 10-20 µM while PL at much lower concentrations only suppressed HCC cell migration/invasion...
March 20, 2015: Oncotarget
https://www.readbyqxmd.com/read/25720297/mycotoxin-zearalenone-induces-apoptosis-in-mouse-leydig-cells-via-an-endoplasmic-reticulum-stress-dependent-signalling-pathway
#18
Pengfei Lin, Fenglei Chen, Jin Sun, Jinhua Zhou, Xiangguo Wang, Nan Wang, Xiao Li, Zhe Zhang, Aihua Wang, YaPing Jin
Zearalenone (ZEN) is a Fusarium mycotoxin that causes several reproductive disorders and genotoxic effects. This study demonstrated the involvement of endoplasmic reticulum (ER) stress in ZEN-induced mouse Leydig cell death. Our study showed that ZEN reduced cell proliferation in a murine Leydig tumour cell line in a dose-dependent manner. The involvement of apoptosis as a major cause of ZEN-induced cell death was further confirmed by the results of a caspase-3 activity assay, which showed a ZEN dose-dependent increase in cell death...
April 2015: Reproductive Toxicology
https://www.readbyqxmd.com/read/25691589/e6-e7-a-novel-splice-isoform-protein-of-human-papillomavirus-16-stabilizes-viral-e6-and-e7-oncoproteins-via-hsp90-and-grp78
#19
Masahiko Ajiro, Zhi-Ming Zheng
UNLABELLED: Transcripts of human papillomavirus 16 (HPV16) E6 and E7 oncogenes undergo alternative RNA splicing to produce multiple splice isoforms. However, the importance of these splice isoforms is poorly understood. Here we report a critical role of E6^E7, a novel isoform containing the 41 N-terminal amino acid (aa) residues of E6 and the 38 C-terminal aa residues of E7, in the regulation of E6 and E7 stability. Through mass spectrometric analysis, we identified that HSP90 and GRP78, which are frequently upregulated in cervical cancer tissues, are two E6^E7-interacting proteins responsible for the stability and function of E6^E7, E6, and E7...
2015: MBio
https://www.readbyqxmd.com/read/25618598/glucose-regulated-protein-78-mediates-the-therapeutic-efficacy-of-17-dmag-in-colon-cancer-cells
#20
Yu-Jia Chang, Chien-Yu Huang, Chin-Sheng Hung, Hui-Hsiung Liu, Po-Li Wei
Glucose-regulated protein 78 (GRP78) is expressed as part of the molecular response to endoplasmic reticulum (ER) stress and mediates protein folding within the cell. GRP78 is also an important biomarker of cancer progression and the therapeutic response of patients with different cancer types. However, the role of GRP78 in the cytotoxic effect of 17-DMAG in colon cancer cells remains unclear. GRP78 expression was knocked down by small interfering RNA (siRNA). The anticancer effects of 17-DMAG were assessed by an 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, a flow cytometric cell-cycle analysis, and an Annexin V-propidium iodide (PI) apoptotic assay...
June 2015: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
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