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https://www.readbyqxmd.com/read/28716523/sensitivity-towards-the-grp78-inhibitor-kp1339-it-139-is-characterized-by-apoptosis-induction-via-caspase-8-upon-disruption-of-er-homeostasis
#1
Beatrix Schoenhacker-Alte, Thomas Mohr, Christine Pirker, Kushtrim Kryeziu, Paul-Steffen Kuhn, Alicia Buck, Thilo Hofmann, Christopher Gerner, Gerrit Hermann, Gunda Koellensperger, Bernhard K Keppler, Walter Berger, Petra Heffeter
The ruthenium drug and GRP78 inhibitor KP1339/IT-139 has already demonstrated promising anticancer activity in a phase I clinical trial. This study aimed to identify mechanisms underlying increased sensitivity to KP1339 treatment. Based on a screen utilizing 23 cell lines, a small panel was selected to compare KP1339-sensitive and low-responsive models. KP1339 sensitivity was neither based on differences in ruthenium accumulation, nor sensitivity to oxidative stress or constituents of KP1339 (ruthenium chloride and indazole)...
July 14, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28715866/protective-effects-of-isorhamnetin-on-n2a-cell-against-endoplasmic-reticulum-stress-induced-injury-is-mediated-by-pkc%C3%AE%C2%B5
#2
Lingyu Qiu, Yurong Ma, Yougen Luo, Zigang Cao, Huiqiang Lu
Endoplasmic reticulum stress (ERS)-induced intracellular calcium (Ca(2+)) overload and ROS burst plays a critical role in apoptosis. Protein kinase C epsilon (PKCε) is involved in regulating the homeostasis of Ca(2+) and ROS production. isorhamnetin (Iso), as an ROS scavenger, effectively inhibit apoptosis, but the mechanism is still unclear. This study was to investigate whether Iso can inhibit ERS-induced apoptosis in N2a cells, and the protective effects are involved in PKCε-mediated Ca(2+) homeostasis and inhibition of ROS...
July 13, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28713986/hydrogen-sulfide-prevents-homocysteine%C3%A2-induced-endoplasmic-reticulum-stress-in-pc12-cells-by-upregulating-sirt%C3%A2-1
#3
Chun-Yan Wang, Wei Zou, Xiao-Yu Liang, Zhi-Sheng Jiang, Xiang Li, Hai-Jun Wei, Yi-Yun Tang, Ping Zhang, Xiao-Qing Tang
It was previously confirmed that hydrogen sulfide (H2S) has a neuroprotective effect, preventing homocysteine‑induced neurotoxicity. However, the exact molecular mechanisms underlying this protective effect remain to be fully elucidated. Endoplasmic reticulum (ER) stress contributes to homocysteine‑induced neurotoxicity. Silent mating type information regulator 2 homolog 1 (SIRT‑1) can attenuate ER stress, exerting its neuroprotective effect. Therefore, the present study aimed to investigate whether H2S protects PC12 cells against homocysteine‑induced ER stress and whether SIRT‑1 mediates this protective effect of H2S...
July 15, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28713984/downregulation-of-microrna%C3%A2-199a%C3%A2-5p-protects-cardiomyocytes-in-cyanotic-congenital-heart-disease-by-attenuating-endoplasmic-reticulum-stress
#4
Yang Zhou, Wei-Kun Jia, Zhao Jian, Liang Zhao, Chen-Cheng Liu, Yong Wang, Ying-Bin Xiao
Chronic hypoxia is a key pathological change in patients with cyanotic congenital heart defect (CCHD). It has been demonstrated that enhanced myocardial unfolded protein response (UPR) increases the capacity to buffer endoplasmic reticulum (ER) stress and to avoid subsequent apoptosis caused by the hypoxia that underlies CCHD. The present study was performed to determine the regulatory role of microRNAs (miRNAs) in this cytoprotective UPR process. The results revealed that miR‑199a‑5p was markedly downregulated in the cardiac tissue of patients with CCHD and in human myocardial cells cultured in hypoxic conditions...
July 6, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28711624/curcumin-attenuates-oxidative-stress-induced-nf%C3%AE%C2%BAb-mediated-inflammation-and-endoplasmic-reticulum-dependent-apoptosis-of-splenocytes-in-diabetes
#5
Kahkashan Rashid, Sayantani Chowdhury, Sumit Ghosh, Parames C Sil
The present study was aimed to determine the curative role of curcumin against diabetes induced oxidative stress and its associated splenic complications. Diabetes was induced in the experimental rats via the intraperitoneal administration of a single dose of STZ (65 mg kg(-1) body weight). Increased blood glucose and intracellular ROS levels along with decreased body weight, the activity of cellular antioxidant enzymes and GSH/GSSG ratio were observed in the diabetic animals. Histological assessment showed white pulp depletion and damaged spleen anatomy in these animals...
July 12, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28709892/liuwei-dihuang-soft-capsules-attenuates-endothelial-cell-apoptosis-to-prevent-atherosclerosis-through-gpr30-mediated-regulation-in-ovariectomized-apoe-deficient-mice
#6
Yi Jing, Danfeng Cai, Qi Chen, Qingping Xiong, Tianhui Hu, Yuan Yao, Chao Lin, Xin Sun, Ying Lu, Xueyun Kong, Xiang Wu, Yu Li, Huimin Bian
ETHNOPHARMACOLOGICAL RELEVANCE: Liuwei Dihuang (LWDH), a classical traditional Chinese medicine prescription, has been widely used to prevent and to treat various diseases with symptoms of 'Kidney-Yin' deficiency syndrome for over 1000 years in China. It is commonly used to treat functional decline associated with senile disease and menopausal syndrome, especially memory decline, insomnia, diabetes and osteoporosis. Modern experimental pharmacological studies indicated that the mechanism of LWDH treatment of menopausal syndrome may be associated with enhanced estrogenic effects...
July 12, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28706146/ros-independent-nrf2-activation-in-prostate-cancer
#7
Ilaria Bellezza, Paolo Scarpelli, Salvatore V Pizzo, Silvia Grottelli, Egidia Costanzi, Alba Minelli
In prostate cancer, oxidative stress and the subsequent Nrf2 activation promote the survival of cancer cells and acquired chemoresistance. Nrf2 links prostate cancer to endoplasmic reticulum stress, an event that triggers the unfolded protein response, aiming to restore cellular homeostasis as well as an adaptive survival mechanism. Glucose-regulated protein of 78 kD /immunoglobulin heavy chain binding protein (GRP78/BiP) is a key molecular chaperone in the endoplasmic reticulum that, when expressed at the cell surface, acts as a receptor for several signaling pathways enhancing antiapoptotic and proliferative signals...
June 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28703940/ebselen-impairs-cellular-oxidative-state-and-induces-endoplasmic-reticulum-stress-and-activation-of-crucial-mitogen-activated-protein-kinases-in-pancreatic-tumour-ar42j-cells
#8
Patricia Santofimia-Castaño, Alicia Izquierdo-Alvarez, María Plaza-Davila, Antonio Martinez-Ruiz, Miguel Fernandez-Bermejo, Jose M Mateos-Rodriguez, Gines M Salido, Antonio Gonzalez
Ebselen (2-phenyl-1,2-benzisoselenazol-3(2H)-one) is an organoselenium radical scavenger compound, which has strong antioxidant and anti-inflammatory effects. However, evidence suggests that this compound could exert deleterious actions on cell physiology. In this study we have analyzed the effect of ebselen on rat pancreatic AR42J cells. Cytosolic free-Ca2(+) concentration ([Ca(2+) ]c ), cellular oxidative status, setting of endoplasmic reticulum stress and phosphorylation of major mitogen-activated protein kinases were analyzed...
July 13, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28701921/endothelial-monocyte-activating-polypeptide-ii-suppresses-the-in-vitro-glioblastoma-induced-angiogenesis-by-inducing-autophagy
#9
Zhiqing Li, Jun Ma, Libo Liu, Xiaobai Liu, Ping Wang, Yunhui Liu, Zhen Li, Jian Zheng, Jiajia Chen, Wei Tao, Yixue Xue
The obstacle in delivering therapeutics to glioblastoma (GBM) is tumor-induced angiogenesis which leads to the formation of abnormal vessels and a dysfunctional blood-tumor barrier. Here, we elucidated the effect of endothelial-monocyte activating polypeptide II (EMAP II) on the GBM-induced angiogenesis as well as its potential mechanisms. Our results proved that EMAP II inhibited the viability, mitochondrial membrane potential, migration and tube formation of GBM-induced endothelial cells (GECs) by inducing cell autophagy, demonstrated by cell viability assay, JC-1 staining assay, transwell assay and tube formation assay, respectively...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28688954/rifampicin-induced-injury-in-hepg2-cells-is-alleviated-by-tudca-via-increasing-bile-acid-transporters-expression-and-enhancing-the-nrf2-mediated-adaptive-response
#10
Weiping Zhang, Lihong Chen, Hui Feng, Wei Wang, Yi Cai, Fen Qi, Xiaofang Tao, Jun Liu, Yujun Shen, Xiaofei Ren, Xi Chen, Jianming Xu, Yuxian Shen
Bile acid transporters and the nuclear factor erythroid 2-related factor (Nrf-2)-mediated adaptive response play important roles in the development of drug-induced liver injury (DILI). However, little is known about the contribution of the adaptive response to rifampicin (RFP)-induced cell injury. In this study, we found RFP decreased the survival rate of HepG2 cells and increased the levels of lactate dehydrogenase (LDH), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (AKP), γ-glutamyl-transferase (γ-GT), total bilirubin (TBIL), direct bilirubin (DBIL), indirect bilirubin (IBIL), total bile acid (TBA) and adenosine triphosphate (ATP) in the cell culture supernatants in both a concentration- and a time-dependent manner...
July 5, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28688153/aqp4-knockout-aggravation-of-isoprenaline-induced-myocardial-injury-is-mediated-by-p66shc-and-endoplasmic-reticulum-stress
#11
Yusi Cheng, Jie Chao, Dezai Dai, Yin Dai, Dongdong Zhu, Bicheng Liu
Aquaporin 4 (AQP4) is a type of water channel protein that maintains the water balance of cardiomyocytes. However, the physiological role of AQP4 in cardiovascular disease is poorly understood. We wanted to explore whether p66Shc and endoplasmic reticulum stress participates in AQP4 knockout (KO)-mediated cardiac injury. There were two types of mice: AQP4 knockout and wild-type mice. Each type was randomly divided into three groups: Control group, isoprenaline stimulation group (ISO, 1 mg/kg, s.c., 5 d), and apocynin treatment group (APO, 100 mg/kg, p...
July 8, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28684299/cyperus-amuricus-induces-g1-arrest-and-apoptosis-through-endoplasmic-reticulum-stress-and-mitochondrial-signaling-in-human-hepatocellular-carcinoma-hep3b-cells
#12
Hai Ha Thi Pham, Yeong-Ae Seong, Daniel Ngabire, Chul-Woong Oh, Gun-Do Kim
ETHNOPHARMACOLOGY RELEVANCE: Cyperus amuricus (C. amuricus), belongs to the family Cyperaceae, was used to exert wound healing, diuretic, astringent and other intestinal problems in oriental medicine. However, only a few studies have reported its anticancer activities. AIM OF THE STUDY: In this study, we determined the activity of C. amuricus on ER stress-induced cell death and G1 cell cycle arrest in human hepatocellular carcinoma (HCC) Hep3B cells. MATERIALS AND METHODS: The in vitro cell proliferation assay of C...
July 4, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28679661/glucose-regulated-protein-78-autoantibody-associates-with-blood-brain-barrier-disruption-in-neuromyelitis-optica
#13
Fumitaka Shimizu, Kristin L Schaller, Gregory P Owens, Anne C Cotleur, Debra Kellner, Yukio Takeshita, Birgit Obermeier, Thomas J Kryzer, Yasuteru Sano, Takashi Kanda, Vanda A Lennon, Richard M Ransohoff, Jeffrey L Bennett
Neuromyelitis optica (NMO) is an inflammatory disorder mediated by antibodies to aquaporin-4 (AQP4) with prominent blood-brain barrier (BBB) breakdown in the acute phase of the disease. Anti-AQP4 antibodies are produced mainly in the periphery, yet they target the astrocyte perivascular end feet behind the BBB. We reasoned that an endothelial cell-targeted autoantibody might promote BBB transit of AQP4 antibodies and facilitate NMO attacks. Using monoclonal recombinant antibodies (rAbs) from patients with NMO, we identified two that strongly bound to the brain microvascular endothelial cells (BMECs)...
July 5, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28678786/bidirectional-interplay-of-hsf1-degradation-and-upr-activation-promotes-tau-hyperphosphorylation
#14
Eunhee Kim, Kazuko Sakata, Francesca-Fang Liao
The unfolded protein response (UPR) in the endoplasmic reticulum (ER) and the cytoplasmic heat stress response are two major stress response systems necessary for maintaining proteostasis for cellular health. Failure of either of these systems, such as in sustained UPR activation or in insufficient heat shock response activation, can lead to the development of neurodegeneration. Alleviation of ER stress and enhancement of heat shock response through heat shock factor 1 (HSF1) activation have previously been considered as attractive potential therapeutic targets for Alzheimer's disease (AD)-a prevalent and devastating tauopathy...
July 5, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28677092/amelioration-of-bleomycin-induced-pulmonary-fibrosis-by-chlorogenic-acid-through-endoplasmic-reticulum-stress-inhibition
#15
Yi-Chun Wang, Jing Dong, Jing Nie, Ji-Xiang Zhu, Hui Wang, Qiong Chen, Jun-Yi Chen, Jia-Mei Xia, Wei Shuai
To investigate the inhibitory effects of chlorogenic acid on pulmonary fibrosis and the internal mechanisms in vivo and in vitro. 30 male BALB/C mice were randomized into 5 groups: control group, pulmonary fibrosis model group, low, middle and high dose of chlorogenic acid groups. Mice in pulmonary fibrosis model group were administered 5.0 mg/kg bleomycin with intracheal instillation and mice in 3 chlorogenic acid groups were treated with chlorogenic acid every day for 28 days after bleomycin administration...
July 4, 2017: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/28675985/hydrogen-alleviates-hyperoxic-acute-lung-injury-related-endoplasmic-reticulum-stress-in-rats-through-upregulation-of-sirt1
#16
Qiang Sun, Wenjie Han, Huijun Hu, Danfeng Fan, Yanbo Li, Yu Zhang, Yan Lv, Mingxin Li, Shuyi Pan
Hyperoxic acute lung injury (HALI) is a major clinical problem for patients undergoing supplemental oxygen therapy. Currently in clinical settings there exist no effective means of prevention or treatment methods. Our previous study found that: hydrogen could reduce HALI, as well as oxidative stress. This research will further explore the mechanism underlying the protective effect of hydrogen on oxygen toxicity. Rats were randomly assigned into three experimental groups and be exposed in oxygen chamber for 60 continuous hours:100% balanced air (control);100% oxygen (HALI);100% oxygen with hydrogen treatment (HALI+HRS)...
July 4, 2017: Free Radical Research
https://www.readbyqxmd.com/read/28664912/a-combined-biomarker-panel-shows-improved-sensitivity-for-the-early-detection-of-ovarian-cancer-allowing-the-identification-of-the-most-aggressive-type-ii-tumours
#17
Matthew R Russell, Ciaren Graham, Alfonsina D'Amato, Aleksandra Gentry-Maharaj, Andy Ryan, Jatinderpal K Kalsi, Carol Ainley, Anthony D Whetton, Usha Menon, Ian Jacobs, Robert L J Graham
BACKGROUND: There is an urgent need for biomarkers for the early detection of ovarian cancer (OC). The purpose of this study was to assess whether changes in serum levels of lecithin-cholesterol acyltransferase (LCAT), sex hormone-binding globulin (SHBG), glucose-regulated protein, 78 kDa (GRP78), calprotectin and insulin-like growth factor-binding protein 2 (IGFBP2) are observed before clinical presentation and to assess the performance of these markers alone and in combination with CA125 for early detection...
June 29, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28664743/mapk-pathway-regulated-the-cardiomyocyte-apoptosis-in-mice-with-post-infarction-heart-failure
#18
Q Zhang, L Lu, T Liang, M Liu, Z L Wang, P Y Zhang
BACKGROUND: To explore the role of the MAPK signaling pathway in the cardiomyocyte apoptosis of mice with post-infarction heart failure (HF). METHODS: Mice were divided into sham and myocardial infarction (MI) groups. Before surgery, the MI group was divided into SB203580 and PBS subgroups. A post-infarction HF model was established by ligating the left anterior descending coronary artery. Ventricular dilatation and cardiac function were observed by small animal echocardiography...
2017: Bratislavské Lekárske Listy
https://www.readbyqxmd.com/read/28662512/ru486-reverses-emotional-disorders-by-influencing-astrocytes-and-endoplasmic-reticulum-stress-in-chronic-restraint-stress-challenged-rats
#19
Liru Dong, Songjun Wang, Yingmin Li, Ziqin Zhao, Yiwen Shen, Li Liu, Guangming Xu, Chunling Ma, Shujin Li, Xiaojing Zhang, Bin Cong
AIMS: To investigate the effect of RU486 (mifepristone) on emotional disorders in chronic restraint stress-induced rats and to explore the mechanisms of that phenomenon. METHODS: For this purpose, 80 healthy male Sprague Dawley rats were randomly divided into four groups: the normal group (Con group, The Con group members received no treatment, eating and drinking freely), the chronic restraint stress group (CRS group, normal Sprague Dawley rats treated with chronic restraint stress, 6 h/day for 21days), the propylene glycol group (CRS+propylene glycol) and the RU486 group (CRS+RU486)...
June 29, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28656194/excessive-nnos-no-ampk-signaling-activation-mediated-by-the-blockage-of-the-cbs-h2s-system-contributes-to-oxygen%C3%A2-glucose-deprivation%C3%A2-induced-endoplasmic-reticulum-stress-in-pc12%C3%A2-cells
#20
Rui Zhang, Yong-Quan Lin, Wei-Sheng Wang, Xin-Qiang Wang
Hypoxic‑ischemia stress causes severe brain injury, leading to death and disability worldwide. Although it has been reported that endoplasmic reticulum (ER) stress is an essential step in the progression of hypoxia or ischemia‑induced brain injury, the underlying molecular mechanisms are and have not yet been fully elucidated. Accumulating evidence has indicated that both nitric oxide (NO) and hydrogen sulfide (H2S) play an important role in the development of cerebral ischemic injury. In the present study, we aimed to investigate the effect of the association between NO signaling and the cystathionine β‑synthase (CBS)/H2S system on ER stress in a cell model of cerebral hypoxia‑ischemia injury...
June 21, 2017: International Journal of Molecular Medicine
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