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regulated IRE-1 dependent

Eun-Jung Park, Yoo-Jin Park, Sangjin Lee, Kyuhong Lee, Cheolho Yoon
Cigarette smoke is responsible for many fatal pulmonary diseases, however, the toxic mechanism is still unclear. In this study, we first confirmed that whole cigarette smoke condensates (WCSC) contain hydrophilic elements, lipophilic and gaseous components. Then, we treated BEAS-2B cells, a normal human bronchial epithelial cell line, at dosages of 0.25, 0.5, and 1% for 24 h and explored the toxic mechanism. Cell viability decreased in a dose-dependent manner, and fission and fusion of mitochondria, damage of endoplasmic reticulume (ER) structures, and formation of autophagosome-like vacuoles were found in cells treated with 1% WCSC...
December 20, 2018: Toxicology Letters
Weituan Xu, Weihua Liu, Wenli Yu
BACKGROUND: Iron is pivotal for life, but it is toxic if in excess. Iron overload mediated by divalent metal transporter 1 (DMT1) in the central nervous system has participated in various neuroinflammatory diseases. Chemokine-induced neuroinflammation involves the development of pathological pain. Recently, chemokine CXCL10 is implicated in the pathogenesis of chronic pain, however, little is known about the potential link between iron accumulation and CXCL10 in pain condition. Here, we examined whether iron accumulation regulated neuropathic pain via CXCL10...
December 3, 2018: Neuroscience Letters
Justin M Long, Bryan Maloney, Jack T Rogers, Debomoy K Lahiri
In addition to the devastating symptoms of dementia, Alzheimer's disease (AD) is characterized by accumulation of the processing products of the amyloid-β (Aβ) peptide precursor protein (APP). APP's non-pathogenic functions include regulating intracellular iron (Fe) homeostasis. MicroRNAs are small (~ 20 nucleotides) RNA species that instill specificity to the RNA-induced silencing complex (RISC). In most cases, RISC inhibits mRNA translation through the 3'-untranslated region (UTR) sequence. By contrast, we report a novel activity of miR-346: specifically, that it targets the APP mRNA 5'-UTR to upregulate APP translation and Aβ production...
November 23, 2018: Molecular Psychiatry
Qinghua Luo, Li Zhang, Feng Wei, Qiang Fang, Fei Bao, Shijiang Mi, Nan Li, Chengming Wang, Yan Liu, Changchun Tu
Classical swine fever virus (CSFV) can utilize diverse host signaling pathways for its replication; however, the cross talk between mammalian target of rapamycin (mTOR) and CSFV remains unknown. Here, we describe the potential role of mTOR complex 1 (mTORC1) in promoting CSFV replication via virus-induced hypophosphorylation of the Akt/mTORC1/S6 pathway, especially at an early stage of viral infection. Conversely, activation of mTORC1 inhibited the replication of CSFV. Furthermore, we revealed the underlying mechanisms of mTORC1 pathway in mediating CSFV replication; in addition, our data also showed that CSFV-induced transient inhibition of mTORC1 elicited a negative feedback activation of PI3K/Akt/mTORC1pathway, likely contributing to maintain the dynamic balance between viral replication and host cell survival...
May 25, 2018: iScience
Lei Yang, Dan Wang, Xue-Ting Wang, Ya-Peng Lu, Li Zhu
BACKGROUND INFORMATION: Divalent metal transporter 1 (DMT1) and transferrin receptor (TfR1) are vital proteins for cellular iron uptake. These proteins have hypoxia-responsive elements (HREs) in their 5'-regulatory region, and they are regulated by hypoxia-inducible factor 1α (HIF-1α) transcriptionally under hypoxic condition. Besides, iron regulatory protein 1 (IRP1) regulates DMT1 and TfR1 by binding to iron-responsive elements (IREs) present in their mRNAs to control cellular iron homeostasis...
December 9, 2018: Biochemical and Biophysical Research Communications
Lan Wang, Xiaopeng Liu, Lin-Hao You, Yun-Zhe Ci, Shiyang Chang, Peng Yu, Guofen Gao, Yan-Zhong Chang
Iron plays an essential role in various cellular metabolic processes of the body. Maintenance of cellular iron homeostasis is particularly important for keeping the normal functions of the cells. Ferroportin 1 (FPN1) is the currently only known iron exporter on the cell membrane. It has been indicated that the regulation of FPN1 in response to the alteration of iron level mainly involves two processes, posttranscriptional repression by iron regulatory proteins (IRPs) and posttranslational degradation by hepcidin, the major iron-sensing hormone...
October 28, 2018: Journal of Cellular Physiology
Qunxiang Shi, Xi Jin, Ruifeng Fan, Mengyuan Xing, Jinming Guo, Ziwei Zhang, Junmin Zhang, Shiwen Xu
Cadmium-mediated microRNAs have become a heavily researched topic. Few studies mention the regulation of autophagy by cadmium through microRNAs, especially regarding poultry. The kidney is one of the organs most severely affected by cadmium, as it is involved in the accumulation of metal ions; causing such types of damage as apoptosis, necrosis and autophagy to the body. However, the relationship between miR-30a and GRP78 in the chicken kidney during ER stress and autophagy via JNK has not been thoroughly elucidated to date...
January 2019: Chemosphere
Jhee Hong Koh, Lei Wang, Caroline Beaudoin-Chabot, Guillaume Thibault
Metabolic disorders such as nonalcoholic fatty liver disease (NAFLD) are emerging epidemics that affect the global population. One facet of these disorders is attributed to the disturbance of membrane lipid composition. Perturbation of endoplasmic reticulum (ER) homeostasis through alteration in membrane phospholipids activates the unfolded protein response (UPR) and causes dramatic transcriptional and translational changes in the cell. To restore cellular homeostasis, the three highly conserved UPR transducers ATF6, IRE1, and PERK mediate adaptive responses upon ER stress...
October 17, 2018: Journal of Cell Science
Jun-Hao Chen, Rui-Hua Zhang, Shao-Li Lin, Peng-Fei Li, Jing-Jing Lan, Sha-Sha Song, Ji-Ming Gao, Yu Wang, Zhi-Jing Xie, Fu-Chang Li, Shi-Jin Jiang
The duck hepatitis A virus type 1 (DHAV-1) is a member of Picornaviridae family, the genome of the virus contains a 5' untranslated region (5' UTR), a large open reading frame that encodes a polyprotein precursor and a 3' UTR followed by a poly(A) tail. The translation initiation of virus proteins depends on the internal ribosome-entry site (IRES) element within the 5' UTR. So far, little information is known about the role of the 3' UTR and poly(A) tail during the virus proliferation. In this study, the function of the 3' UTR and poly(A) tail of DHAV-1 in viral replication and IRES-mediated translation was investigated...
2018: Frontiers in Microbiology
Kazuhiro Iwai
Because of essentiality and toxicity of iron in our body, iron metabolism is tightly regulated in cells. In mammalian cells, iron regulatory protein 1 and 2 (IRP1 and IRP2) are the central regulators of cellular iron metabolism. IRPs regulate iron metabolism by interacting with the RNA stem-loop structures, iron-responsive elements (IREs), found on the transcripts encoding proteins involved in iron metabolism only in iron depleted condition. It is also well-known that the ubiquitin system plays central roles in cellular iron regulation because both IRPs having the IRE binding activity are recognized and ubiquitinated by the SCFFBXL5 ubiquitin ligase in condition of iron-replete...
September 12, 2018: Free Radical Biology & Medicine
C Joaquín Cáceres, Jenniffer Angulo, Fernando Lowy, Nataly Contreras, Beth Walters, Eduardo Olivares, Delphine Allouche, Anne Merviel, Karla Pino, Bruno Sargueil, Sunnie R Thompson, Marcelo López-Lastra
Human T-cell leukemia virus type 1 (HTLV-1) is the etiological agent of adult T-cell leukemia (ATL). The HTLV-1 basic leucine zipper protein (HBZ) is expressed in all cases of ATL and is directly associated with virus pathogenicity. The two isoforms of the HBZ protein are synthesized from antisense messenger RNAs (mRNAs) that are either spliced (sHBZ) or unspliced (usHBZ) versions of the HBZ transcript. The sHBZ and usHBZ mRNAs have entirely different 5'untranslated regions (5'UTR) and are differentially expressed in cells, with the sHBZ protein being more abundant...
November 16, 2018: Nucleic Acids Research
Yang Yang, Chenfeng Wang, Kailiang Zhao, Guang Zhang, Decai Wang, Yide Mei
The tumor suppressor p53 plays a pivotal role in the protection against cancer. Increasing evidence suggests that long noncoding RNA (lncRNA) plays an important role in the regulation of the p53 pathway, however, the detailed mechanisms remain to be further elucidated. In this study, we report a new p53-inducible lncRNA that we termed TRMP (TP53-regulated modulator of p27). As a direct transcriptional target of p53, TRMP plays an unexpected pro-survival function. Knockdown of TRMP inhibits cell proliferation by inducing a G1 cell cycle arrest...
August 30, 2018: Cell Death & Disease
Vivek Venkataramani, Thorsten R Doeppner, Desiree Willkommen, Catherine M Cahill, Yongjuan Xin, Guilin Ye, Yanyan Liu, Adam Southon, Allegra Aron, Ho Yu Au-Yeung, Xudong Huang, Debomoy K Lahiri, Fudi Wang, Ashley I Bush, Gerald G Wulf, Philipp Ströbel, Bernhard Michalke, Jack T Rogers
For more than 150 years it is known that occupational overexposure of manganese (Mn) causes movement disorders resembling Parkinson's disease (PD) and PD-like syndromes. However, the mechanisms of Mn toxicity are still poorly understood. Here, we demonstrate that Mn dose- and time-dependently blocks the protein translation of amyloid precursor protein (APP) and heavy-chain Ferritin (H-Ferritin), both iron homeostatic proteins with neuroprotective features. APP and H-Ferritin are post-transcriptionally regulated by iron responsive proteins (IRPs), which bind to homologous iron responsive elements (IREs) located in the 5'-untranslated regions (5'-UTRs) within their mRNA transcripts...
August 27, 2018: Journal of Neurochemistry
Carlo Mangia, Alice Vismarra, Marco Genchi, Sara Epis, Claudio Bandi, Giulio Grandi, Lesley Bell-Sakyi, Domenico Otranto, Benedetta Passeri, Laura Kramer
BACKGROUND: Over-expression of ATP-binding cassette (ABC) transporter proteins has been implicated in resistance of ticks to acaricides. Tick cell lines are useful for investigating resistance mechanisms, as development of an in vitro model for the study of acaricide resistance would contribute to improving knowledge of the molecular basis behind drug processing and exclusion in ticks. In the present study, cultures of the Ixodes ricinus-derived cell line IRE/CTVM19 were treated with the acaricides amitraz, permethrin or fipronil to determine modulation of ABC transporter gene expression...
July 31, 2018: Parasites & Vectors
Megan A Peppenelli, Michael J Miller, Aaron M Altman, Olesea Cojohari, Gary C Chan
Primary peripheral blood monocytes are responsible for the hematogenous dissemination of human cytomegalovirus (HCMV) following a primary infection. In order to facilitate viral spread, HCMV extends the naturally short 48-h lifespan of monocytes by stimulating a non-canonical activation of Akt during viral entry, which leads to the increased expression of a specific subset of antiapoptotic proteins. In this study, global analysis of the Akt signaling network showed HCMV induced a more robust activation of the entire network when compared to normal myeloid growth factors...
October 2018: Antiviral Research
Shuang-Shuang Yang, Jigui Wang, Zhaoda Li, Shangjin Cui, Weiquan Liu
Mink enteritis virus (MEV), as a parvovirus, is among the smallest of the animal DNA viruses. The limited genome leads to multifunctional sequences and complex gene expression regulation. Here, we show that the expression of viral capsid protein 2 (VP2) of MEV requires its 5' untranslated regions (5' UTR) which promote VP2 gene expression at both transcriptional and translational levels. The expression of VP2 was inhibited in several common eukaryotic expression vectors. Our data showed that the 5' UTR of VP2 enhanced capsid gene transcription but not increased stability or promotes nucleocytoplasmic export of VP2 mRNA...
September 15, 2018: Journal of Virology
Ram Kumar, Nitin Khandelwal, Riyesh Thachamvally, Bhupendra Nath Tripathi, Sanjay Barua, Sudhir Kumar Kashyap, Sunil Maherchandani, Naveen Kumar
Viruses are obligate intracellular parasites; they heavily depend on the host cell machinery to effectively replicate and produce new progeny virus particles. Following viral infection, diverse cell signaling pathways are initiated by the cells, with the major goal of establishing an antiviral state. However, viruses have been shown to exploit cellular signaling pathways for their own effective replication. Genome-wide siRNA screens have also identified numerous host factors that either support (proviral) or inhibit (antiviral) virus replication...
July 15, 2018: Virus Research
Fabrizio Damiano, Mariangela Testini, Romina Tocci, Gabriele V Gnoni, Luisa Siculella
Acetyl-CoA carboxylase 1 (ACC1) is a cytosolic enzyme catalyzing the rate limiting step in de novo fatty acid biosynthesis. There is mounting evidence showing that ACC1 is susceptible to dysregulation and that it is over-expressed in liver diseases associated with lipid accumulation and in several cancers. In the present study, ACC1 regulation at the translational level is reported. Using several experimental approaches, the presence of an internal ribosome entry site (IRES) has been established in the 5' untranslated region (5' UTR) of the ACC1 mRNA...
April 2018: Biochimica et biophysica acta. Molecular and cell biology of lipids
Yanling Yan, Conghui Li, Binlian Sun, Rongge Yang
Hepatitis C virus (HCV) is a worldwide threaten to human health with a high ratio of chronic infections. Recently, we found that Vpr-mediated regulation of HCV replication depends on the host protein DDB1-Cul4 associate factor 1 (DCAF1), implying that DCAF1 might be involved in the replication of HCV. In this study, we demonstrated that DCAF1 knockdown reduced HCV replication both in the infectious (JFH1) and replicon (Con1) systems. Further investigation showed a negative regulation of HCV internal ribosome entry site (IRES)-mediated translation by DCAF1...
April 2018: Archives of Virology
Lin Li, Jiahui Cui, Zi Liu, Xuejiao Zhou, Zengqiang Li, Yang Yu, Yuanyuan Jia, Daiying Zuo, Yingliang Wu
Silver nanoparticles (AgNPs) have many medical and commercial applications, but their effects on human health are poorly understood. The aim of this study was to assess the effect of AgNPs on the human neuroblastoma cell line SH-SY5Y and to explore their potential mechanisms of action. We found that AgNPs decreased SH-SY5Y cell viability in a dose- and time-dependent manner. Exposure to AgNPs activated endoplasmic reticulum (ER) stress, as reflected by upregulated expression of glucose-regulated protein 78 (GRP78), phosphorylated PKR-like endoplasmic reticulum kinase (p-PERK), phosphorylated eukaryotic translation initiation factor 2α (p-eIF2α), C/EBP homology protein (CHOP), spliced X-box binding protein-1 (XBP1), and phosphorylated inositol-requiring enzyme (p-IRE), all of which are involved in the cellular unfolded protein response...
March 15, 2018: Toxicology Letters
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