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https://www.readbyqxmd.com/read/28333162/the-endoplasmic-reticulum-chaperone-grp78-bip-modulates-prion-propagation-in-vitro-and-in-vivo
#1
Kyung-Won Park, Gyoung Eun Kim, Rodrigo Morales, Fabio Moda, Ines Moreno-Gonzalez, Luis Concha-Marambio, Amy S Lee, Claudio Hetz, Claudio Soto
Prion diseases are fatal neurodegenerative disorders affecting several mammalian species, characterized by the accumulation of the misfolded form of the prion protein, which is followed by the induction of endoplasmic reticulum (ER) stress and the activation of the unfolded protein response (UPR). GRP78, also called BiP, is a master regulator of the UPR, reducing ER stress levels and apoptosis due to an enhancement of the cellular folding capacity. Here, we studied the role of GRP78 in prion diseases using several in vivo and in vitro approaches...
March 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28326487/enhanced-stim1-expression-is-associated-with-acquired-chemo-resistance-of-cisplatin-in-osteosarcoma-cells
#2
Xilong Sun, Qiang Wei, Jie Cheng, Yanzhu Bian, Congna Tian, Yujing Hu, Huijie Li
Osteosarcoma is the most common primary malignant bone tumor. Although cisplatin is the primary chemotherapy used in osteosarcoma treatment, the cisplatin resistance remains a big challenge for improving overall survival. The store-operated calcium (Ca(2+)) entry (SOCE) and its major mediator Stim1 have been shown to be implicated in a number of pathological processes typical for cancer. In this study, we showed that Stim1 expression was significantly increased in chemo-resistant osteosarcoma tissues compared with chemo-sensitivity tissues...
March 22, 2017: Human Cell
https://www.readbyqxmd.com/read/28320302/high-level-soluble-expression-and-atpase-characterization-of-human-heat-shock-protein-grp78
#3
Shuang Wu, Hongpeng Zhang, Miao Luo, Ke Chen, Wei Yang, Lei Bai, Ailong Huang, Deqiang Wang
Human GRP78 has been shown to promote cancer progression and is regarded as a novel target for anticancer drugs. However, generation of recombinant full-length GRP78 remains challenging. This report demonstrates that E. coli autoinduction is an excellent method for the preparation of active recombinant GRP78 protein. The final yield was approximately 50 mg/liter of autoinduction culture. Gel-filtration experiments confirmed that the chaperone is a monomer. The purified human GRP78 catalyzed the conversion of ATP to ADP without requiring metal ions as cofactors...
February 2017: Biochemistry. Biokhimii︠a︡
https://www.readbyqxmd.com/read/28303260/evidence-for-an-additive-neurorestorative-effect-of-simultaneously-administered-cdnf-and-gdnf-in-hemiparkinsonian-rats-implications-for-different-mechanism-of-action
#4
Merja H Voutilainen, Francesca De Lorenzo, Polina Stepanova, Susanne Bäck, Li-Ying Yu, Päivi Lindholm, Eeva Pörsti, Mart Saarma, Pekka T Männistö, Raimo K Tuominen
Parkinson's disease (PD) is a neurodegenerative disorder associated with a progressive loss of dopaminergic (DAergic) neurons of the substantia nigra (SN) and the accumulation of intracellular inclusions containing α-synuclein. Current therapies do not stop the progression of the disease, and the efficacy of these treatments wanes over time. Neurotrophic factors (NTFs) are naturally occurring proteins promoting the survival and differentiation of neurons and the maintenance of neuronal contacts. CDNF (cerebral dopamine NTF) and GDNF (glial cell line-derived NTF) are able to protect DAergic neurons against toxin-induced degeneration in experimental models of PD...
January 2017: ENeuro
https://www.readbyqxmd.com/read/28303170/tbhq-alleviated-endoplasmic-reticulum-stress-apoptosis-and-oxidative-stress-by-perk-nrf2-crosstalk-in-methamphetamine-induced-chronic-pulmonary-toxicity
#5
Yun Wang, Yu-Han Gu, Ming Liu, Yang Bai, Li-Ye Liang, Huai-Liang Wang
Methamphetamine (MA) leads to cardiac and pulmonary toxicity expressed as increases in inflammatory responses and oxidative stress. However, some interactions may exist between oxidative stress and endoplasmic reticulum stress (ERS). The current study is designed to investigate if both oxidative stress and ERS are involved in MA-induced chronic pulmonary toxicity and if antioxidant tertiary butylhydroquinone (TBHQ) alleviated ERS-apoptosis and oxidative stress by PERK-Nrf2 crosstalk. In this study, the rats were randomly divided into control group, MA-treated group (MA), and MA plus TBHQ-treated group (MA + TBHQ)...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28296042/nickel-sulfate-induced-apoptosis-via-activating-ros-dependent-mitochondria-and-endoplasmic-reticulum-stress-pathways-in-rat-leydig-cells
#6
Lingyue Zou, Li Su, Yifan Sun, Aijie Han, Xuhong Chang, An Zhu, Fangfang Liu, Jin Li, Yingbiao Sun
Nickel can induce apoptosis of testicular Leydig cells in mice, whereas the mechanisms remain unclear. In this study, we investigated the role of nickel-induced reactive oxygen species (ROS) generation in mitochondria and endoplasmic reticulum stress (ERS) mediated apoptosis pathways in rat Leydig cells. Fluorescent DCF and Annexin-V FITC/PI staining were performed to measure the production of ROS and apoptosis in Leydig cells. RT-qPCR and Western blot were conducted to analyze the key genes and proteins involved in mitochondria and ERS apoptotic pathways...
March 15, 2017: Environmental Toxicology
https://www.readbyqxmd.com/read/28287102/plumbagin-sensitizes-breast-cancer-cells-to-tamoxifen-induced-cell-death-through-grp78-inhibition-and-bik-upregulation
#7
Anna Kawiak, Anna Domachowska, Anna Jaworska, Ewa Lojkowska
The glucose regulated protein 78 (GRP78) is a major chaperone of the endoplasmic reticulum, and a prosurvival component of the unfolded protein response. GRP78 is upregulated in many types of cancers, including breast cancer. Research has suggested that GRP78 overexpression confers chemoresistance to anti-estrogen agents through a mechanism involving the inhibition of a pro-apoptotic BH3-only protein, Bik. In the present research the role of plumbagin, a naturally occurring naphthoquinone, in GRP78-associated cell death inhibition was examined...
March 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28282906/gsk3%C3%AE-and-vdac-involvement-in-er-stress-and-apoptosis-modulation-during-orthotopic-liver-transplantation
#8
Mohamed Amine Zaouali, Arnau Panisello, Alexandre Lopez, Carlos Castro, Emma Folch, Teresa Carbonell, Anabela Rolo, Carlos Marques Palmeira, Agustin Garcia-Gil, René Adam, Joan Roselló-Catafau
We investigated the involvement of glycogen synthase kinase-3β (GSK3β) and the voltage-dependent anion channel (VDAC) in livers subjected to cold ischemia-reperfusion injury (I/R) associated with orthotopic liver transplantation (OLT). Rat livers were preserved in University of Wisconsin (UW) and Institute Georges Lopez (IGL-1) solution, the latter enriched or not with trimetazidine, and then subjected to OLT. Transaminase (ALT) and HMGB1 protein levels, glutamate dehydrogenase (GLDH), and oxidative stress (MDA) were measured...
March 8, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28277984/neutral-sphingomyelinase-inhibition-alleviates-apoptosis-but-not-er-stress-in-liver-ischemia-reperfusion-injury
#9
Hazal Tuzcu, Betul Unal, Ebru Kırac, Esma Konuk, Filiz Ozcan, Gulsum O Elpek, Necdet Demir, Mutay Aslan
Previous studies have revealed the activation of neutral sphingomyelinase (N-SMase)/ceramide pathway in hepatic tissue following warm liver ischemia reperfusion (IR) injury. Excessive ceramide accumulation is known to potentiate apoptotic stimuli and a link between apoptosis and endoplasmic reticulum (ER) stress has been established in hepatic IR injury. Thus, this study determined the role of selective N-SMase inhibition on ER stress and apoptotic markers in a rat model of liver IR injury. Selective N-SMase inhibitor was administered via intraperitoneal injections...
March 13, 2017: Free Radical Research
https://www.readbyqxmd.com/read/28275724/mitochondrial-metabolic-regulation-by-grp78
#10
Manoj Prasad, Kevin J Pawlak, William E Burak, Elizabeth E Perry, Brendan Marshall, Randy M Whittal, Himangshu S Bose
Steroids, essential for mammalian survival, are initiated by cholesterol transport by steroidogenic acute regulatory protein (StAR). Appropriate protein folding is an essential requirement of activity. Endoplasmic reticulum (ER) chaperones assist in folding of cytoplasmic proteins, whereas mitochondrial chaperones fold only mitochondrial proteins. We show that glucose regulatory protein 78 (GRP78), a master ER chaperone, is also present at the mitochondria-associated ER membrane (MAM), where it folds StAR for delivery to the outer mitochondrial membrane...
February 2017: Science Advances
https://www.readbyqxmd.com/read/28271591/a-novel-heterozygous-mutation-of-the-wfs1-gene-leading-to-constitutive-endoplasmic-reticulum-stress-is-the-cause-of-wolfram-syndrome
#11
Shuntaro Morikawa, Toshihiro Tajima, Akie Nakamura, Katsura Ishizu, Tadashi Ariga
BACKGROUND: Wolfram syndrome (WS) is a disorder characterized by the association of insulin-dependent diabetes mellitus (DM), diabetes insipidus, deafness, and optic nerve atrophy. WS is caused by WFS1 mutations encoding WFS1 protein expressed in endoplasmic reticulum (ER). During ER protein synthesis, misfolded and unfolded proteins accumulate, known as "ER stress". This is attenuated by the unfolded protein response (UPR), which recovers and maintains ER functions. Because WFS1 is a UPR component, mutant WFS1 might cause unresolvable ER stress conditions and cell apoptosis, the major causes underlying WS symptoms...
March 8, 2017: Pediatric Diabetes
https://www.readbyqxmd.com/read/28260037/negative-regulation-of-erk1-2-by-pi3k-is-required-for-the-protective-effects-of-pyropia-yezoensis-peptide-against-perfluorooctane-sulfonate-induced-endoplasmic-reticulum-stress
#12
Jeong Hwan Oh, Eun-Young Kim, Youn Hee Choi, Taek-Jeong Nam
Perfluorooctane sulfonate (PFOS) is a stable fluorosurfactant, which causes adverse effects in various organisms. The present study was designed to investigate the effects of Pyropia yezoensis peptide (PYP), a peptide comprised of 11 residues (ALEGGKSSGGG), on PFOS-induced endoplasmic reticulum (ER) stress in Chang cells. PFOS exposure (400 µM) for 24 h significantly decreased cell viability, which was upregulated by 250‑1,000 pg/ml PYP treatment. Exposure to PFOS also significantly increased expression of the ER stress response protein, glucose-regulated protein 78 (GRP78), and phosphorylation of extracellular signal‑regulated kinase 1/2 (ERK1/2)...
March 3, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28259956/protective-effects-of-hydrogen-sulfide-against-angiotensin%C3%A2-ii-induced-endoplasmic-reticulum-stress-in-huvecs
#13
Heng-Jing Hu, Zhi-Sheng Jiang, Jie Qiu, Sheng-Hua Zhou, Qi-Ming Liu
The inhibitory effects of hydrogen sulfide (H2S) on angiotensin II (AngII)-stimulated human umbilical vein endothelial cell (HUVEC) dysfunction remain to be elucidated. Endoplasmic reticulum (ER) stress has been detected in endothelial dysfunction (ED). The present study aimed to determine whether H2S may exert an inhibitory effect on AngII‑induced ER stress. Using HUVECs as a model system, the present study used western blotting to detect protein expression, intracellular reactive oxygen species (ROS) levels were determined by oxidative conversion of cell permeable DCFH‑DA to fluorescent dichlorofluorescein, CCK‑8 assay was used to investigate the cell viability, methylene blue was used to investigate the CSE activity, TUNEL was used to investigate the cells apoptosis...
February 22, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28258248/caf-derived-hgf-promotes-cell-proliferation-and-drug-resistance-by-up-regulating-the-c-met-pi3k-akt-and-grp78-signaling-in-ovarian-cancer-cells
#14
De Ying Wei, Feng Geng, Shu Mei Liang, Hui Zhao, Ming Liu, Hong Qing Wang
The tumor microenvironment which is a highly heterogeneous entity plays crucial roles in cancer progression. As the most prominent stromal cell types, cancer-associated fibroblasts (CAFs) produce a variety of factors into the tumor microenvironment. In this study, we firstly isolated CAFs from tumor tissues of the patients with ovarian cancer and demonstrated that hepatocyte growth factor (HGF) was highly expressed in the supernatant of CAFs. CAF-derived HGF or human recombinant HGF promoted cell proliferation in human ovarian cell lines SKOV3 and HO-8910 cells...
March 3, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/28255266/lipocalin-2-promotes-endoplasmic-reticulum-stress-and-proliferation-by-augmenting-intracellular-iron-in-human-pulmonary-arterial-smooth-muscle-cells
#15
Guoliang Wang, Shenghua Liu, Li Wang, Liukun Meng, Chuanjue Cui, Hao Zhang, Shengshou Hu, Ning Ma, Yingjie Wei
Endoplasmic reticulum (ER) stress, a feature of many conditions associated with pulmonary hypertension (PH), is increasingly recognized as a common response to promote proliferation in the walls of pulmonary arteries. Increased expression of Lipocalin-2 in PH led us to test the hypothesis that Lipocalin-2, a protein known to sequester iron and regulate it intracellularly, might facilitate the ER stress and proliferation in pulmonary arterial smooth muscle cells (PASMCs). In this study, we observed greatly increased Lcn2 expression accompanied with increased ATF6 cleavage in a standard rat model of pulmonary hypertension induced by monocrotaline...
2017: International Journal of Biological Sciences
https://www.readbyqxmd.com/read/28249225/cadmium-induced-endoplasmic-reticulum-stress-in-chicken-neutrophils-is-alleviated-by-selenium
#16
Jianqiao Chen, Tingru Pan, Na Wan, Zhepeng Sun, Ziwei Zhang, Shu Li
Cadmium (Cd) decreases immune function and induces apoptosis of immune cells. Selenium (Se) can antagonize some metal element toxicity including Cd. To evaluate the cytotoxicity of Cd and the chemoprotective role of Se on bird neutrophils in vitro, we incubated chicken neutrophils cells with Cadmium chloride (CdCl2) (10(-6)M), Sodium selenite (Na2SeO3) (10(-7)M), and with a mixture of Na2SeO3 (10(-7)M) and CdCl2 (10(-6)M) for 12, 24, 36, and 48h. We found that Interleukin 1β (IL-1β), Interleukin 10 (IL-10), and interferon gamma (IFN-γ) increased and interleukin 17 (IL-17), interleukin 4 (IL-4) decreased significantly in the chicken neutrophils of the Cd treatment groups...
February 24, 2017: Journal of Inorganic Biochemistry
https://www.readbyqxmd.com/read/28245171/mir-181a-inhibits-cervical-cancer-development-via-downregulating-grp78
#17
Chengyan Luo, Jiangnan Qiu
Cervical is among one of the top common cancers of women worldwide. Understanding the pathological mechanisms of cervical cancer development is critical for identifying novel targets for cervical cancer treatment. microRNAs (miRs) have various roles in regulating cancer development. Here, we investigated the potential roles of miR-181a and its target in regulating cervical cancer development and chemotherapy resistance. Expression of miR-181a was evaluated and modulated in several human cervical cancer cell lines...
February 13, 2017: Oncology Research
https://www.readbyqxmd.com/read/28240761/hepatocellular-carcinoma-and-cxcr3-chemokines-a-narrative-review
#18
E Giusy, F Poupak
Hepatocellular carcinoma (HCC) results from several factors like viral hepatitis infection [hepatitis B, or C (25%)] or occupational exposure. T-helper (Th)1 inflammatory cells, characterized by interferon (IFN)-γ and interleukin (IL)-2 secretion, predominate in the liver during chronic HCV infection, and chemokines attracting these cells are particularly important in disease progression. Among C-X-C chemokines, the non-ELR group [as IFN-γ-induced protein 10 (IP-10), monokine induced by IFN-γ (MIG) and IFN-inducible T-cell-alpha chemoattractant (I-TAC)], attracts Th1-cells interacting with chemokine C-X-C receptor (CXCR3)...
January 2017: La Clinica Terapeutica
https://www.readbyqxmd.com/read/28238876/ar-12-suppresses-dengue-virus-replication-by-down-regulation-of-pi3k-akt-and-grp78
#19
Hsin-Hsin Chen, Chien-Chin Chen, Yee-Shin Lin, Chiou-Feng Lin, Chia-Ling Chen, Chih-Peng Chang
Dengue virus (DENV) infection has become a public health issue of worldwide concern and is a serious health problem in Taiwan, yet there are no approved effective antiviral drugs to treat DENV. The replication of DENV requires both viral and cellular factors. Owing to the rapid mutation rate of viral factors, targeting host factors may serve as a more promising antiviral strategy. It has been known that up-regulation of PI3K/AKT signaling and GRP78 by DENV infection supports its replication. AR-12, a phase I trial completed anticancer drug, shows potent inhibitory activities on both PI3K/AKT signaling and GRP78 expression levels, and recently has been found to block the replication of several hemorrhagic fever viruses...
February 23, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28237821/relief-of-oxidative-stress-and-cardiomyocyte-apoptosis-by-using-curcumin-nanoparticles
#20
Jing Li, Yu Zhou, Wei Zhang, Cuiyu Bao, Zhigang Xie
In this work, the influence of curcumin nanoparticles (CUR-NPs) on NADPH oxidase-related reactive oxygen species (ROS) production and cardiac apoptosis, together with the modulation of protein signaling pathways, were investigated in detail by using cardiomyocytes. The exposure of cardiomyocytes to palmitate (PA) led to an increase in both cell apoptosis and intracellular ROS levels, which were strongly inhibited by CUR-NPs. CUR-NPs treatment remarkably suppressed the increased activity of Rac1, as well as the enhanced expression of p22(phox), p47(phox), p67(phox) and gp91(phox) induced by PA...
February 21, 2017: Colloids and Surfaces. B, Biointerfaces
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