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https://www.readbyqxmd.com/read/28916474/nox4-regulates-the-enos-uncoupling-process-in-aging-endothelial-cells
#1
Hwa-Young Lee, Hyung-Ryong Kim, Han-Jung Chae
ROS and its associated signaling contribute to vascular aging-associated endothelial disturbance. Since the non-effective endothelial nitric oxide synthase (eNOS) coupling status is related to vascular aging-related phenotypes, eNOS coupled/uncoupled system signaling was studied in human umbilical vein endothelial cells (HUVEC). Nitric oxide (NO) and eNOS Ser1177 were significantly decreased, whereas O2(-) (superoxide anion radical) increased with passage number. In aging cells, NADPH oxidase 4 (Nox4), one of the main superoxide generating enzymes, and its associated protein disulfide isomerase (PDI) chaperone were highly activated, and the resultant ER redox imbalance leads to disturbance of protein folding capability, namely endoplasmic reticulum (ER) stress, ultimately inducing dissociation between HSP90 and IRE-1α or PERK, decreasing HSP90 stability and dissociating the binding of eNOS from the HSP90 and leading to eNOS uncoupling...
September 12, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28916354/abnormal-sodium-channel-mrna-splicing-in-hypertrophic-cardiomyopathy
#2
Adam M Noyes, Anyu Zhou, Ge Gao, Lianzhi Gu, Sharlene Day, J Andrew Wasserstrom, Samuel C Dudley
BACKGROUND: Our previous studies showed that in ischemic and nonischemic heart failure (HF), the voltage-gated cardiac Na(+) channel α subunit (SCN5A) mRNA is abnormally spliced to produce two truncated transcript variants (E28C and D) that activate the unfolded protein response (UPR). We tested whether SCN5A post-transcriptional regulation was abnormal in hypertrophic cardiomyopathy (HCM). MATERIAL AND METHODS: Human heart tissue was obtained from HCM patients...
September 7, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/28915706/the-role-of-autophagy-in-hepatocellular-carcinoma-friend-or-foe
#3
REVIEW
Lian Liu, Jia-Zhi Liao, Xing-Xing He, Pei-Yuan Li
Autophagy is an evolutionarily conserved lysosome-dependent catabolic process which degrades cell's components in order to recycle substrates to exert optimally and adapt to tough circumstances. It is a critical cellular homeostatic mechanism with stress resistance, immunity, antiaging, and pro-tumor or anti-tumor effects. Among these, the role of autophagy in cancer is the most eye-catching that is not immutable but dynamic and highly complex. Basal autophagy acts as a tumor suppressor by maintaining genomic stability in normal cells...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28915629/ier3ip1-deficiency-leads-to-increased-%C3%AE-cell-death-and-decreased-%C3%AE-cell-proliferation
#4
Juan Sun, Decheng Ren
Mutations in the gene for Immediate Early Response 3 Interacting Protein 1 (IER3IP1) cause permanent neonatal diabetes mellitus in human. The mechanisms involved have not been determined and the role of IER3IP1 in β-cell survival has not been characterized. In order to determine if there is a molecular link between IER3IP1 deficiency and β-cell survival and proliferation, we knocked down Ier3ip1 gene expression in mouse MIN6 insulinoma cells. IER3IP1 suppression induced apoptotic cell death which was associated with an increase in Bim and a decrease in Bcl-xL...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28903445/predicting-clinical-benefit-from-everolimus-in-patients-with-advanced-solid-tumors-the-cpct-03-study
#5
Fleur Weeber, Geert A Cirkel, Marlous Hoogstraat, Sander Bins, Christa G M Gadellaa-van Hooijdonk, Salo Ooft, Erik van Werkhoven, Stefan M Willems, Marijn van Stralen, Wouter B Veldhuis, Nicolle J M Besselink, Hugo M Horlings, Neeltje Steeghs, Maja J de Jonge, Marlies H G Langenberg, Lodewyk F A Wessels, Edwin P J G Cuppen, J H Schellens, Stefan Sleijfer, Martijn P Lolkema, Emile E Voest
BACKGROUND: In this study, our aim was to identify molecular aberrations predictive for response to everolimus, an mTOR inhibitor, regardless of tumor type. METHODS: To generate hypotheses about potential markers for sensitivity to mTOR inhibition, drug sensitivity and genomic profiles of 835 cell lines were analyzed. Subsequently, a multicenter study was conducted. Patients with advanced solid tumors lacking standard of care treatment options were included and underwent a pre-treatment tumor biopsy to enable DNA sequencing of 1,977 genes, derive copy number profiles and determine activation status of pS6 and pERK...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28901411/palmitate-induces-myocardial-lipotoxic-injury-via-the-endoplasmic-reticulum-stress%C3%A2-mediated-apoptosis-pathway
#6
Lu Zou, Xiaoyan Li, Nan Wu, Pengyu Jia, Chunting Liu, Dalin Jia
Increased free fatty acids in cardiomyocytes induce myocardial lipotoxic injury, but the underlying mechanisms are not well understood. Therefore, the aim of the present study was to explore the role of the endoplasmic reticulum (ER) stress‑mediated apoptosis pathway in palmitate (PA)‑induced cardiomyocyte lipotoxicity. H9c2 cells were treated with various doses (100, 200 and 400 µM) of PA to mimic cardiomyocyte lipotoxicity in vitro. Oil Red O staining was used to determine the accumulation of intracellular lipids...
August 31, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28901409/epigallocatechin%C3%A2-3%C3%A2-gallate-protects-from-high-glucose-induced-podocyte-apoptosis-via-suppressing-endoplasmic-reticulum-stress
#7
Chunhong Xiang, Xiaoyan Xiao, Bei Jiang, Mengkun Zhou, Yidan Zhang, Hui Li, Zhao Hu
Podocytes serve a critical role in the development of many glomerular diseases, including diabetic nephropathy (DN). Epigallocatechin‑3‑gallate (EGCG), a predominant polyphenolic component of green tea, has indicated its therapeutic effects in diabetes. In the present study, mouse podocyte cells were cultured in vitro, cell injury was induced by high glucose, and the protective effect of EGCG on cell proliferation and apoptosis and the underlying mechanisms were investigated. The results demonstrated that high glucose significantly inhibited cell proliferation after 48 and 72 h compared with normal glucose and mannitol treatment...
August 29, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28899505/an-alkaloid-extract-obtained-from-phlegmariurus-saururus-induces-neuroprotection-after-status-epilepticus
#8
Víctor Danelon, Laura Montroull, Mariana Vallejo, José Cabrera, Alicia Agnese, María Gabriela Ortega, Daniel Mascó
BACKGROUND: The brain is exposed to many excitotoxic insults that can lead to neuronal damage. Among these, Epilepsy is a neurological disease that affects a large percentage of world population and is commonly associated with cognitive disorders and excitotoxic neuronal death. Most experimental strategies are focused on preventing Status Epilepticus (SE), but once it has already occurred, the key question is whether it is possible to save neurons. PURPOSE: The aim of this study was to determine if a purified alkaloid extract (AE) obtained from Phlegmariurus saururus, a genus of Lycophyte plants (sometimes known as firmossesor fir club mosses) could induce neuroprotection following SE...
October 15, 2017: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/28895799/protective-effects-of-bellidifolin-in-hypoxia-induced-in-pheochromocytoma-cells-pc12-and-underlying-mechanisms
#9
Zhi-Ying Zhao, Yang-Yang Gao, Li Gao, Ming Zhang, He Wang, Chun-Hong Zhang
Bellidifolin, a xanthone compound derived from plants of Gentiana species, is known to exert a variety of pharmacological activities including anti-oxidation, anti-inflammatory and antitumor actions as well as a protective effect on cerebral ischemic nerve injury. The aim of this study was to examine the protective effects of bellidifolin on nerve injury produced by hypoxia and possible underlying mechanisms using pheochromocytoma cells (PC12). Data showed that the viability of PC12 cells subjected to hypoxia resulted in a significant decrease; however; pretreatment with certain concentrations of bellidifolin (20 or 40 μmol/L) prior to hypoxia significantly increased the survival rate...
September 12, 2017: Journal of Toxicology and Environmental Health. Part A
https://www.readbyqxmd.com/read/28893685/protective-effects-of-a-g-lucidum-proteoglycan-on-ins-1-cells-against-iapp-induced-apoptosis-via-attenuating-endoplasmic-reticulum-stress-and-modulating-chop-jnk-pathways
#10
Yan-Ming He, Qiang Zhang, Min Zheng, Zhao-Hua Fan, Yun-Hao Li, Dan Zhang, Zeng Zhang, Sha-Sha Yuan, Yan-Yan Wang, Ping Zhou, Hong-Jie Yang
Fudan-Yueyang-G. lucidum (FYGL) is a water-soluble macromolecular proteoglycan extracted from Ganoderma lucidum which has been used for health promotion for a long time in China. The aim of this study was to investigate the protective effects of FYGL on INS-1 rat insulinoma beta cells against IAPP-induced cell apoptosis, as well as the underlying mechanisms. The results showed that apoptotic cells were significantly increased when incubated with islet amyloid polypeptide (IAPP). However, cytotoxicity of IAPP was significantly attenuated by co-incubation of the cells with FYGL...
September 8, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28888981/hypoxia-in-3t3-l1-adipocytes-suppresses-adiponectin-expression-via-the-perk-and-ire1-unfolded-protein-response
#11
Qian Guo, Sanli Jin, Hailong Hu, Ying Zhou, Yuheng Yan, He Zong, Yu Wang, Hongjuan He, Yuri Oh, Chuanpeng Liu, Ning Gu
Adiponectin, an adipocytokine produced by adipocytes, functions as an anti-inflammatory and anti-apoptotic substance, while also enhancing insulin sensitivity. Patients or model animals with obesity or diabetes typically present attenuated expression of adiponectin. Moreover, obesity and diabetes are often accompanied with hypoxia in adipose tissue, which may result in endoplasmic reticulum (ER) stress as well as low expression of adiponectin. The purpose of this study was to investigate the specific role of the unfolded protein response (UPR) involved in the low expression of adiponectin induced by hypoxia...
September 6, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28885098/rosuvastatin-inhibits-high-glucose-stimulated-upregulation-of-vcam-1-via-the-mapk-signalling-pathway-in-endothelial-cells
#12
Moo Hyun Kim, Chae-Eun Kim, Sung-Whan Kim
OBJECTIVE: The aim of this study is to investigate the molecular mechanisms and effect of rosuvastatin on adhesion molecule induction in human endothelial cells under high-glucose conditions (HG). METHODS AND RESULTS: The effects of rosuvastatin on vascular cell adhesion molecule (VCAM)-1 production and pERK phosphorylation were measured in HG-induced human umbilical vein endothelial cells (HUVECs) with inhibitors targeting the mitogen-activated protein kinase (MAPK) signal pathway...
September 8, 2017: Acta Cardiologica
https://www.readbyqxmd.com/read/28883998/endoplasmic-reticulum-stress-and-unfolded-protein-response-in-infection-by-intracellular-parasites
#13
REVIEW
Luca Galluzzi, Aurora Diotallevi, Mauro Magnani
Perturbations of the physiological status of the endoplasmic reticulum (ER) trigger a specific response known as the ER stress response or unfolded protein response (UPR). In mammalian cells, the UPR is mediated by three ER transmembrane proteins (IRE1, PERK and ATF6) which activate three signaling cascades to restore ER homeostasis. In recent years, a cross-talk between UPR, inflammatory and microbial sensing pathways has been elucidated. Pathogen infection can lead to UPR activation; moreover, several pathogens subvert the UPR to promote their survival and replication...
August 2017: Future Science OA
https://www.readbyqxmd.com/read/28882789/litopenaeus-vannamei-activating-transcription-factor-6-alpha-gene-involvement-in-er-stress-response-and-white-spot-symptom-virus-infection
#14
Kai Yuan, Hong-Hui He, Chao-Zheng Zhang, Xiao-Yun Li, Shao-Ping Weng, Jian-Guo He, Yi-Hong Chen
A previous study found that inositol-requiring enzyme-1-X-box binding protein 1 (IRE1-XBP1) pathway and the protein kinase RNA (PKR)-like ER kinase-eIF2α (PERK-eIF2α) pathway of shrimp play roles in the unfolded protein response (UPR). And they also be proved that was involved in white spot symptom virus (WSSV) infection. Yet the functions of the third branch in shrimp UPR are still unclear. In this study, we showed that upon UPR activation, activating transcription factor 6 alpha (LvATF6α) of Litopenaeus vannamei was cleaved and transferred from the cytoplasm to the nucleus in 293T cells, indicating that the ATF6 pathway in shrimp is also a branch of UPR...
September 4, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28881751/hepatitis-b-virus-surface-proteins-accelerate-cholestatic-injury-and-tumor-progression-in-abcb4-knockout-mice
#15
Daniel Zahner, Hannah Glimm, Tomomitsu Matono, Yuri Churin, Diran Herebian, Ertan Mayatepek, Kernt Köhler, Stefan Gattenlöhner, Anne Stinn, Annette Tschuschner, Martin Roderfeld, Elke Roeb
Understanding of the pathophysiology of cholestasis associated carcinogenesis could challenge the development of new personalized therapeutic approaches and thus improve prognosis. Simultaneous damage might aggravate hepatic injury, induce chronic liver disease and even promote carcinogenesis. We aimed to study the effect of Hepatitis B virus surface protein (HBsAg) on cholestatic liver disease and associated carcinogenesis in a mouse model combining both impairments. Hybrids of Abcb4(-/-) and HBsAg transgenic mice were bred on fibrosis susceptible background BALB/c...
August 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28881710/experimental-african-trypanosome-infection-suppresses-the-development-of-multiple-myeloma-in-mice-by-inducing-intrinsic-apoptosis-of-malignant-plasma-cells
#16
Nathan De Beule, Eline Menu, Mathieu J M Bertrand, Mérédis Favreau, Elke De Bruyne, Ken Maes, Kim De Veirman, Magdalena Radwanska, Afshin Samali, Stefan Magez, Karin Vanderkerken, Carl De Trez
Multiple myeloma (MM) is characterized by the accumulation of malignant plasma cells in the bone marrow (BM). Recently, several studies have highlighted the role of pathogens in either promoting or dampening malignancies of unrelated origin. Trypanosoma brucei is an extracellular protozoan parasite which causes sleeping sickness. Our group has previously demonstrated that trypanosome infection affects effector plasma B cells. Therefore, we hypothesized that T. brucei infection could have an impact on MM development...
August 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28881660/activation-of-perk-branch-of-er-stress-mediates-homocysteine-induced-bkca-channel-dysfunction-in-coronary-artery-via-foxo3a-dependent-regulation-of-atrogin-1
#17
Wen-Tao Sun, Xiang-Chong Wang, Shiu-Kwong Mak, Guo-Wei He, Xiao-Cheng Liu, Malcolm John Underwood, Qin Yang
The molecular mechanism of endoplasmic reticulum (ER) stress in vascular pathophysiology remains inadequately understood. We studied the role of ER stress in homocysteine-induced impairment of coronary dilator function, with uncovering the molecular basis of the effect of ER stress on smooth muscle large-conductance Ca(2+)-activated K(+) (BKCa) channels. The vasodilatory function of BKCa channels was studied in a myograph using endothelium-denuded porcine small coronary arteries. Primary cultured porcine coronary artery smooth muscle cells were used for mRNA and protein measurements and current recording of BKCa channels...
August 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28875043/the-role-of-endoplasmic-reticulum-stress-in-cardiovascular-disease-and-exercise
#18
REVIEW
Junyoung Hong, Kwangchan Kim, Jong-Hee Kim, Yoonjung Park
Endoplasmic reticulum (ER) stress, which is highly associated with cardiovascular disease, is triggered by a disturbance in ER function because of protein misfolding or an increase in protein secretion. Prolonged disruption of ER causes ER stress and activation of the unfolded protein response (UPR) and leads to various diseases. Eukaryotic cells respond to ER stress via three major sensors that are bound to the ER membrane: activating transcription factor 6 (ATF6), inositol-requiring protein 1α (IRE1α), and protein kinase RNA-like ER kinase (PERK)...
2017: International Journal of Vascular Medicine
https://www.readbyqxmd.com/read/28871429/elucidating-the-rapid-action-of-2-2-chlorophenyl-ethylbiguanide-on-ht-29-cells-under-a-serum-and-glucose-deprived-condition
#19
Kentaro Oh-Hashi, Shiori Matsumoto, Takayuki Sakai, Yuki Nomura, Kensuke Okuda, Hideko Nagasawa, Yoko Hirata
We recently demonstrated the cytotoxic action of a novel phenformin derivative, 2-(2-chlorophenyl)ethylbiguanide (2-Cl-Phen), on HT-29 cells under a serum- and glucose-deprived condition. In that study, we showed that the ATF6 arm of the ER stress pathway and c-Myc expression were downregulated 12 h after the treatment with 2-Cl-Phen. Through characterization of intracellular events at the early phase of the 2-Cl-Phen treatment before noticeable morphological changes, we found rapid fluctuations in the c-Myc and ATF4 proteins but not in their mRNAs in 2-Cl-Phen-treated HT-29 cells under the serum- and glucose-deprived condition...
September 5, 2017: Cell Biology and Toxicology
https://www.readbyqxmd.com/read/28870808/hedgehog-signaling-inhibitor-gant61-induces-endoplasmic-reticulum-stress-mediated-protective-autophagy-in-hepatic-stellate-cells
#20
Jie Li, Lingmin Zhang, Qingqing Xia, Junhui Fu, Zhijun Zhou, Feng Lin
Hedgehog (Hh) signaling plays an important role in the viability maintenance of hepatic stellate cells (HSC). HSCs have been identified as the major profibrogenic cells in the liver. The present study revealed that a novel Hh antagonist GANT61 induced apoptosis in the activated human hepatic stellate cell line LX-2 cells, as it dose-dependently caused mitochondrial inner transmembrane potential (ΔΨm) loss and caspase-3 cleavage. Autophagic flux was markedly increased after GANT61 treatment in LX-2 cells...
September 1, 2017: Biochemical and Biophysical Research Communications
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