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Yimeng Hu, Jie Liu, Yin Yuan, Jing Chen, Siyuan Cheng, Huawei Wang, Yancheng Xu
Sodium butyrate (NaB), a histone deacetylase (HDAC) inhibitors, has been reported to attenuate hyperglycemia in rats. Our objective was to explore the effect and underlying mechanism of NaB on islet β-cell dysfunction and apoptosis in type 2 diabetic (T2DM) rats. T2DM models were induced by the combination of streptozotocin (STZ, 40 mg/kg) and high-fat-diet, while NaB (500 mg/kg/d) was intraperitoneally injected for 6 weeks in experimental groups. Our results suggested NaB mitigated hyperglycemia, lowered the levels of serum cholestenone (TC) and low-density lipoprotein (LDL-c), prevented body weight loss, and enhanced insulin resistance and glucose tolerance...
September 6, 2018: Environmental Toxicology and Pharmacology
Hairong Xin, Yintian Deng, Jie Cao
Gastric cancer is one of the most fatal cancers worldwide. The incidence and death rates are still increasing for gastric cancer. Increasing studies have shown that proviral insertion in murine lymphomas 2 (PIM2) functions as critical regulator of multiple cancers. However, it remains unknown whether and how PIM2 regulates gastric cancer progression. In this study, PIM2 was increased in the gastric cancer tissues of patients. Patients with high PIM2 expression levels had significantly shorter survival than those with low PIM2 expression...
October 16, 2018: Biochemical and Biophysical Research Communications
Daiha Shin, Eun Hye Kim, Jaewang Lee, Jong-Lyel Roh
Glutathione peroxidase 4 (GPX4) is a regulator of ferroptosis (iron-dependent, non-apoptotic cell death); its inhibition can render therapy-resistant cancer cells susceptible to ferroptosis. However, some cancer cells develop mechanisms protective against ferroptosis; understanding these mechanisms could help overcome chemoresistance. In this study, we investigated the molecular mechanisms underlying resistance to ferroptosis induced by GPX4 inhibition in head and neck cancer (HNC). The effects of two GPX4 inhibitors, (1S, 3R)-RSL3 and ML-162, and of trigonelline were tested in HNC cell lines, including cisplatin-resistant (HN3R) and acquired RSL3-resistant (HN3-rslR) cells...
October 16, 2018: Free Radical Biology & Medicine
Elias Zgheib, Alice Limonciel, Xiaoqi Jiang, Anja Wilmes, Steven Wink, Bob van de Water, Annette Kopp-Schneider, Frederic Y Bois, Paul Jennings
Toxicological responses to chemical insult are largely regulated by transcriptionally activated pathways that may be independent, correlated and partially or fully overlapping. Investigating the dynamics of the interactions between stress responsive transcription factors from toxicogenomic data and defining the signature of each of them is an additional step toward a system level understanding of perturbation driven mechanisms. To this end, we investigated the segregation of the genes belonging to the three following transcriptionally regulated pathways: the AhR pathway, the Nrf2 pathway and the ATF4 pathway...
2018: Frontiers in Genetics
Baimei He, Qiong Chen, Dongbo Zhou, Lijing Wang, Zhaoqian Liu
Endoplasmic reticulum stress (ERS)-induced apoptosis of airway epithelial cells plays an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD). Furthermore, autophagy is closely related to ERS under apoptosis. Here, this study aimed to investigate the role of the reciprocal interaction between autophagy and ERS in the cigarette smoke extract (CSE)-induced apoptosis of human bronchial epithelial (HBE) cells. Cell apoptosis was detected by flow cytometry analysis. Protein expression was examined by Western blot...
October 17, 2018: IUBMB Life
Duxan Arancibia, Pedro Zamorano, María Estela Andrés
The Cerebral Dopamine Neurotrophic Factor (CDNF) is a neurotrophic factor that has a protective effect in cell and animal models of several neurodegenerative diseases. The molecular mechanism of the protective effect of CDNF is unclear. Many neurodegenerative diseases have been related to a proteostasis dysregulation in the endoplasmic reticulum (ER). A failure of proteostasis produces ER stress, triggering the unfolded protein response (UPR) and, in the long-term, induces cell death. An adaptive UPR solves ER stress by attenuating protein synthesis, inducing chaperones expression, and degradation of misfolded proteins...
November 2018: Biochimica et biophysica acta. Molecular cell research
Liu Xin, Wu Fan, Du Tingting, Sun Zuoming, Zhang Qiang
PURPOSE: To investigate the effect of 4-phenylbutyric acid (4-PBA) on intermittent hypoxia (IH)-induced liver cell injury and to clarify the underlying mechanisms. METHODS: L02 cells (normal human liver cells) were cultured in normoxic condition or subjected to intermittent hypoxia for 4, 8, and 12 h. A part of hypoxia-treated L02 cells was applied with 4-PBA 1 h before exposure to hypoxia. The effect of 4-PBA on liver injury, hepatocyte apoptosis, endoplasmic reticulum stress (ERS), and PERK-eIFa2-ATF4-CHOP apoptotic pathway was investigated...
October 15, 2018: Sleep & Breathing, Schlaf & Atmung
Hye-Bin Park, Mi-Jeong Kim, Bae-Dong Jung, Seunghyung Lee, Choon-Keun Park, Boo-Keun Yang, Hee-Tae Cheong
We investigate the effect of endoplasmic reticulum (ER) stress inhibitor treatment during parthenogenetic activation of oocytes on the ER stress generation, apoptosis, and in vitro development of parthenogenetic porcine embryos. Porcine in vitro matured oocytes were activated by 1) electric stimulus (E) or 2) E+10 μM Ca-ionophore (A23187) treatment (EC). Oocytes were then treated by ER stress inhibitors such as salubrinal (200 nM) and tauroursodeoxychloic acid (TUDCA, 100 μM) for 3 h prior to in vitro culture...
September 2018: Balsaeng'gwa Saengsig
Huimin Hu, Changyuan Wang, Yue Jin, Qiang Meng, Qi Liu, Zhihao Liu, Kexin Liu, Xiaoyu Liu, Huijun Sun
Hyperhomocysteinemia (HHCY) has been recognized as an independent risk factor for atherosclerosis and plays a vital role in the development of atherosclerosis. Catalpol, an iridoid glucoside extracted from the root of Rehmannia glutinosa, can produce anti-inflammatory, anti-oxidant, anti-tumor, and dopaminergic neurons protecting effects. This study aimed to determine the protecting effects of catalpol against homocysteine (HCY)-induced injuries in human aortic endothelial cells (HAECs) and uncover the underlying mechanisms: 1...
October 12, 2018: Inflammation
Katherine R Sadleir, Jelena Popovic, Robert Vassar
Alzheimer's disease (AD) mouse models that overexpress amyloid precursor protein (APP) and presenilin 1 (PS1) form β-amyloid (Aβ) plaques, a hallmark AD lesion. It has been assumed that the neuroinflammation, synaptic dysfunction, neurodegeneration, and cognitive impairment observed in these mice are caused by cerebral Aβ accumulation. However, it is also possible that accumulation of overexpressed transmembrane proteins APP and PS1 in the endoplasmic reticulum (ER) triggers chronic ER stress and activation of the unfolded protein response (UPR)...
October 12, 2018: Journal of Biological Chemistry
Liang-Che Chang, Tzu-Ping Chen, Wei-Ke Kuo, Chung-Ching Hua
Introduction: The expression of programmed death 1 (PD1) and programmed death ligand 1 (PDL1) can be induced by the interferon (IFN)/signal transducer and activator of transcription (STAT) pathway. The PD1/PDL1 reverse signaling can activate the eukaryotic translation initiation factor 2 (eIF2 α )/activating transcription factor 4 (ATF4) pathway which in turn regulates the expression of IFN regulatory factor (IRF) 7 and IFN α . The eIF2 α /ATF4 pathway is responsible for the integrated stress response (ISR) of unfolded protein response (UPR) which can affect immune cell function in tumor microenvironment...
2018: Disease Markers
Gnana P Krishnamoorthy, Natalie R Davidson, Steven D Leach, Zhen Zhao, Scott W Lowe, Gina Lee, Iñigo Landa, James Nagarajah, Mahesh Saqcena, Kamini Singh, Hans-Guido Wendel, Snjezana Dogan, Prasanna P Tamarapu, John Blenis, Ronald Ghossein, Jeffrey A Knauf, Gunnar Rätsch, James A Fagin
Translation initiation is orchestrated by the cap binding and 43S pre-initiation complexes (PIC). Eukaryotic initiation factor 1A (EIF1A) is essential for recruitment of the ternary complex and for assembling the 43S PIC. Recurrent EIF1AX mutations in papillary thyroid cancers are mutually exclusive with other drivers, including RAS. EIF1AX is enriched in advanced thyroid cancers, where it displays a striking co-occurrence with RAS, which cooperates to induce tumorigenesis in mice and isogenic cell lines. The C-terminal EIF1AX-A113splice mutation is the most prevalent in advanced thyroid cancer...
October 10, 2018: Cancer Discovery
Emi Ooe, Yoshiki Kuse, Tomohiro Yako, Tetsuya Sogon, Shinsuke Nakamura, Hideaki Hara, Masamitsu Shimazawa
Purpose: The purpose of this study was to investigate the effects of bilberry extract with its anthocyanins on retinal photoreceptor cell damage and on the endoplasmic reticulum (ER) stress induced by exposure to blue light-emitting diode (LED) light. Methods: Cultured murine photoreceptor cells (661W) were exposed to blue LED light with or without bilberry extract or its anthocyanins in the culture media. Aggregated short-wavelength opsin (S-opsin) in murine photoreceptor cells was observed with immunostaining...
2018: Molecular Vision
Abigael Cheruiyot, Shan Li, Andrew Nickless, Robyn Roth, James A J Fitzpatrick, Zhongsheng You
The nonsense mediated RNA decay (NMD) pathway safeguards the integrity of the transcriptome by targeting mRNAs with premature translation termination codons (PTCs) for degradation. It also regulates gene expression by degrading a large number of non-mutant RNAs (including mRNAs and noncoding RNAs) that bear NMD-inducing features. Consequently, NMD has been shown to influence development, cellular response to stress, and clinical outcome of many genetic diseases. Small molecules that can modulate NMD activity provide critical tools for understanding the mechanism and physiological functions of NMD, and they also offer potential means for treating certain genetic diseases and cancer...
2018: PloS One
Sylvain Le Pape, Ophélie Pasini-Chabot, Pierre Couturier, Pierre-Olivier Delpech, Romain Volmer, Nathalie Quellard, Rutger Ploeg, Thierry Hauet, Raphaël Thuillier
The relationship between cold ischaemia time (CIT) and adverse outcome is now acknowledged. However, the underlying mechanisms remain to be defined, which slows the development of adapted therapeutics and diagnostics. We explored the impact of CIT in both preclinical and in vitro models of preservation. We determined that the endoplasmic reticulum (ER) and its stress response (unfolded protein response, UPR) were regulated in close association with CIT; the eIF2α-ATF4 pathway was inhibited early (1-8 h) at the detriment of cell survival, while the ATF6 pathway was activated late (12-24 h) and associated with cell death...
October 3, 2018: Artificial Cells, Nanomedicine, and Biotechnology
E C Dos Santos, R Varchetta, C B de Lima, J Ispada, H S Martinho, P K Fontes, M F G Nogueira, B Gasparrini, M P Milazzotto
The earliest stages of embryo development are deeply influenced by reactive oxygen species (ROS), byproducts of the mitochondrial oxygen metabolism that play a key role as messengers in normal cell signal transduction and cell cycling. Despite its positive roles, the imbalance caused by the excess of ROS and an inefficient antioxidant system leads to oxidative stress, with negative consequences to the cell such as DNA damage, metabolic changes, mitochondrial stress and cell death. In the present work, crocetin - a natural antioxidant - was added to the culture media of bovine embryos to evaluate the efficiency of its antioxidant capability during embryo culture...
August 8, 2018: Theriogenology
Mario R Fernandez, John L Cleveland
No abstract text is available yet for this article.
October 15, 2018: EMBO Journal
Rajapaksha Gedara Prasad Tharanga Jayasooriya, Matharage Gayani Dilshara, Wisurumuni Arachchilage Hasitha Maduranga Karunarathne, Ilandarage Menu Neelaka Molagoda, Yung Hyun Choi, Gi-Young Kim
Camptothecin (CPT) from Camptotheca acuminate was discovered for anticancer drugs, which targets topoisomease I. However, whether CPT regulates c-Myc expression has not been understood in endoplasmic reticulum (ER) stress and autophagy. In this study, we found that CPT enhanced c-Myc expression and that the transient knockdown of c-Myc abrogated reactive oxygen species (ROS) generation, which resulted in the accumulation of ER stress-regulating proteins, such as PERK, eIF2α, ATF4, and CHOP. Moreover, the transfection of eIF2α-targeted siRNA attenuated CPT-induced autophagy and decreased the levels of Beclin-1 and Atg7, which indicated that CPT upregulated ER stress-mediated autophagy...
September 25, 2018: Food and Chemical Toxicology
Xue Wang, Hua-Ying Xia, Hong-You Qin, Xiang-Ping Kang, Hai-Yan Hu, Jing Zheng, Jia-Ye Jiang, Ling-Ai Yao, Yan-Wu Xu, Tong Zhang, Xue-Li Zhang
20(S)-protopanaxadiol (PPD)-type ginsenosides are generally believed to be the most pharmacologically active components of Panax ginseng. These compounds induce apoptotic cell death in various cancer cells, which suggests that they have anti-cancer activity. Anti-angiogenesis is a promising therapeutic approach for controlling angiogenesis-related diseases such as malignant tumors, age-related macular degeneration, and atherosclerosis. Studies showed that 20(S)-PPD at low concentrations induces endothelial cell growth, but in our present study, we found 20(S)-PPD at high concentrations inhibited cell growth and mediated apoptosis in human umbilical vein endothelial cells (HUVECs)...
September 26, 2018: Journal of Cellular Biochemistry
Szabolcs Felszeghy, Johanna Viiri, Jussi J Paterno, Juha M T Hyttinen, Ali Koskela, Mei Chen, Henri Leinonen, Heikki Tanila, Niko Kivinen, Arto Koistinen, Elisa Toropainen, Marialaura Amadio, Adrian Smedowski, Mika Reinisalo, Mateusz Winiarczyk, Jerzy Mackiewicz, Maija Mutikainen, Anna-Kaisa Ruotsalainen, Mikko Kettunen, Kimmo Jokivarsi, Debasish Sinha, Kati Kinnunen, Goran Petrovski, Janusz Blasiak, Geir Bjørkøy, Ari Koskelainen, Heli Skottman, Arto Urtti, Antero Salminen, Ram Kannan, Deborah A Ferrington, Heping Xu, Anna-Liisa Levonen, Pasi Tavi, Anu Kauppinen, Kai Kaarniranta
Age-related macular degeneration (AMD) is a multi-factorial disease that is the leading cause of irreversible and severe vision loss in the developed countries. It has been suggested that the pathogenesis of dry AMD involves impaired protein degradation in retinal pigment epithelial cells (RPE). RPE cells are constantly exposed to oxidative stress that may lead to the accumulation of damaged cellular proteins, DNA and lipids and evoke tissue deterioration during the aging process. The ubiquitin-proteasome pathway and the lysosomal/autophagosomal pathway are the two major proteolytic systems in eukaryotic cells...
September 14, 2018: Redox Biology
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