728 research outputs found
Bioinformatics analysis of evolution and human disease related transposable element-derived microRNAs
No full textTransposable element (TE) has the ability to insert into certain parts of the genome, and due to this event, it is possible for TEs to generate new factors and one of these factors are microRNAs (miRNA). miRNAs are non-coding RNAs made up of 19 to 24 nucleotides and numerous miRNAs are derived from TE. In this study, to support general knowledge on TE and miRNAs derived from TE, several bioinformatics tools and databases were used to analyze miRNAs derived from TE in two aspects: evolution and human disease. The distribution of TEs in diverse species presents that almost half of the genome is covered with TE in mammalians and less than a half in other vertebrates and invertebrates. Based on selected evolution-related miRNAs studies, a total of 51 miRNAs derived from TE were found and analyzed. For the human disease-related miRNAs, total of 34 miRNAs derived from TE were organized from the previous studies. In summary, abundant miRNAs derived from TE are found, however, the function of miRNAs derived from TE is not informed either. Therefore, this study provides theoretical understanding of miRNAs derived from TE by using various bioinformatics tools.
Isoliquiritigenin reduces LPS-induced inflammation by preventing mitochondrial fission in BV-2 microglial cells
No full textExcessive microglial cell activation in the brain can lead to the production of various neurotoxic factors (e.g., pro-inflammatory cytokines, nitric oxide) which can, in turn, initiate neurodegenerative processes. Recent research has been reported that mitochondrial dynamics regulate the inflammatory response of lipopolysaccharide (LPS). Isoliquiritigenin (ISL) is a compound found in Glycyrrhizae radix with anti-inflammatory and antioxidant properties. In this study, we investigated the function of ISL on the LPS-induced pro-inflammatory response in BV-2 microglial cells. We showed that ISL reduced the LPS-induced increase in pro-inflammatory mediators (e.g., nitric oxide and pro-inflammatory cytokines) via the inhibition of ERK/p38/NF-κB activation and the generation of reactive oxygen species (ROS). Furthermore, ISL inhibited the excessive mitochondrial fission induced by LPS, regulating mitochondrial ROS generation and pro-inflammatory response by suppressing the calcium/calcineurin pathway to dephosphorylate Drp1 at the serine 637 residue. Interestingly, the ISL pretreatment reduced the number of apoptotic cells and levels of cleaved caspase3/PARP, compared to LPS-treated cells. Our findings suggested that ISL ameliorated the pro-inflammatory response of microglia by inhibiting dephosphorylation of Drp1 (Ser637)-dependent mitochondrial fission. This study provides the first evidence for the effects of ISL against LPS-induced inflammatory response related and its link to mitochondrial fission and the calcium/calcineurin pathway. Consequently, we also identified the protective effects of ISL against LPS-induced microglial apoptosis, highlighting the pharmacological role of ISL in microglial inflammation-mediated neurodegeneration.
Transcriptional variations mediated by an alternative promoter of the FPR3 gene
No full textFormyl peptide receptor 3 (FPR3) is a potential player in innate immunity and appears with FPR2 as a FPR cluster during primate evolution. Comparative genome analyses indicate that a segmental duplication (SD) event upstream of the FPR3 gene after the divergence of New and Old World monkeys led to the emergence of an alternative promoter. In this study we combined computational and experimental approaches to identify a FPR3 gene that is controlled by an alternative promoter derived during a SD event. Its transcriptional activity was detected by quantitative reverse transcription polymerase chain reaction. Human alternative transcripts (FPR3-1 and FPR3-2) showed tissue-specific patterns with strong expressions in lung or uterus, while the FPR3-1 transcript of rhesus macaque is broadly expressed in various tissues. Overall, transcriptional variations of FPR3 occur by an alternative promoter during primate evolution.open
Placenta-restricted expression of LTR-derived NOS3
No full textDomestication events of long terminal repeat (LTR) sequences of the human endogenous retrovirus (HERV) family have been considered to be a new mechanism for the generation of alternative splicing in the human genome. We investigated an LTR10A belonging to the HERV-I family at the human endothelial nitric oxide synthase (NOS3) gene locus. The LTR10A element was located upstream of the original promoter sequences of NOS3. Expression analysis using RT-PCR and reporter gene assays in HCT116 and COS7 cells indicated placenta-specific expression of NOS3 driven by the LTR10A-derived promoter. The placenta-restricted expression was also determined to be associated with hypomethylation of the LTR10A element by methylation analysis using sodium bisulfite DNA sequencing. Furthermore, treatment of brain-derived cell lines with demethylation reagents did not restore expression of the LTR-derived NOS3 gene transcript. Taken together, the integration event of an LTR10A element in the upstream region of NOS3 led to the generation of a placenta-specific alternative transcript governed by cooperative mechanisms of epigenetic control (DNA methylation) and transcriptional regulation (interaction between cis- and trans-acting elements).open
Neural Signals Related to Outcome Evaluation Are Stronger in CA1 than CA3
No full textWe have shown previously that CA1 conveys significant neural signals necessary to update value of the chosen target, namely chosen value and reward signals. To better understand hippocampal neural processes related to valuation, we compared chosen value- and reward-related neural activity between the CA3 and CA1 regions. Single units were recorded with tetrodes from the dorsal CA3 and CA1 regions of rats performing a dynamic foraging task, and chosen value- and reward-related neural activity was estimated using a reinforcement learning model and multiple regression analyses. Neural signals for chosen value and reward converged in both CA3 and CA1 when a trial outcome was revealed. However, these neural signals were stronger in CA1 than CA3. Consequently, neural signals for reward prediction error and updated chosen value were stronger in CA1 than CA3. Together with our previous finding that CA1 conveys stronger value signals than the subiculum, our results raise the possibility that CA1 might play a particularly important role among hippocampal subregions in evaluating experienced events. © 2017 Lee, Huh, Lee, Ghim, Lee and Jung. © 2017 Lee, Huh, Lee, Ghim, Lee and Jung. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Copyright © 2017 Lee, Huh, Lee, Ghim, Lee and Jung. This is an open-access article
distributed under the terms of the Creative Commons Attribution License (CC BY).
The use, distribution or reproduction in other forums is permitted, provided the
original author(s) or licensor are credited and that the original publication in this
journal is cited, in accordance with accepted academic practice. No use, distribution
or reproduction is permitted which does not comply with these terms.1221Nsciescopu
Peroxiredoxin 2 deficiency reduces white adipogenesis due to the excessive ROS generation
No full textReactive oxygen species (ROS) act as signaling molecules to regulate various cell functions. Numerous studies have demonstrated ROS to be essential for the differentiation of adipocytes. Peroxiredoxins (Prxs) are a ubiquitous family of antioxidant enzymes in mammalian cells. Prx2 is present in the cytoplasm and cell membranes and demonstrates ROS scavenging activity. We focused on Prx2 involvement in regulating adipogenesis and lipid accumulation and demonstrated that Prx2 expression was upregulated during adipocyte differentiation. In addition, the silencing of Prx2 (shPrx2) inhibited adipogenesis by modulating adipogenic gene expression, and cell death was enhanced via increased ROS production in shPrx2？3T3？L1 cells. These results demonstrate that shPrx2 triggers adipocyte cell death and weakens adipocyte function via ROS production. Taken together, our data suggest the participation of Prx2 in adipocyte function and differentiation. Our results also imply that the downregulation of Prx2 activity could help prevent obesity. Overall, findings support the development of ROS？based therapeutic solutions for the treatment of obesity and obesity？related metabolic disorders.
Peroxiredoxin 5 ameliorates obesity-induced non-alcoholic fatty liver disease through the regulation of oxidative stress and AMP-activated protein kinase signaling
No full textNon-alcoholic fatty liver disease (NAFLD) is becoming the most common chronic liver disease globally. NAFLD？which can develop into liver fibrosis, nonalcoholic steatohepatosis, cirrhosis, and hepatocellular carcinoma？is defined as an excess accumulation of fat caused by abnormal lipid metabolism and excessive reactive oxygen species (ROS) generation in hepatocytes. Recently, we reported that Peroxiredoxin 5 (Prx5) plays an essential role in regulating adipogenesis and suggested the need to further investigation on the potential curative effects of Prx5 on obesity-induced fatty liver disease. In the present study, we focused on the role of Prx5 in fatty liver disease. We found that Prx5 overexpression significantly suppressed cytosolic and mitochondrial ROS generation. Additionally, Prx5 regulated the AMP-activated protein kinase pathway and lipogenic gene (sterol regulatory element binding protein-1 and FAS) expression; it also inhibited lipid accumulation, resulting in the amelioration of free fatty acid-induced hepatic steatosis. Silence of Prx5 triggered de novo lipogenesis and abnormal lipid accumulation in HepG2 cells. Concordantly, Prx5 knockout mice exhibited a high susceptibility to obesity-induced hepatic steatosis. Liver sections of Prx5-deletion mice fed on a high-fat diet displayed Oil Red O-stained dots and small leaky shapes due to immoderate fat deposition. Collectively, our findings suggest that Prx5 functions as a protective regulator in fatty liver disease and that it may be a valuable therapeutic target for the management of obesity-related metabolic diseases. ⓒ 2019 The Authors
Peroxiredoxin 4 attenuates glutamate-induced neuronal cell death through inhibition of endoplasmic reticulum stress
No full textHigh concentrations of glutamate induce neurotoxicity by eliciting reactive oxygen species (ROS) generation and intracellular Ca2+ influx. The disruption of Ca2+ homeostasis in the endoplasmic reticulum (ER) evokes ER stress, ultimately resulting in neuronal dysfunction. Additionally, glutamate participates in the development of neurodegenerative diseases, such as Alzheimer’s and Parkinson’s diseases. Peroxiredoxins (Prxs) are members of a family of antioxidant enzymes that protect cells from neurotoxic factor-induced apoptosis by scavenging hydrogen peroxide (H2O2). Prx4 is located in the ER and controls the redox condition within the ER. The present study investigated the protective effects of Prx4 against glutamate-induced neurotoxicity linked to ER stress. HT22 cells in which Prx4 was either overexpressed or silenced were used to elucidate the protective role of Prx4 against glutamate toxicity. The expression of Prx4 in HT22 cells was significantly increased in response to glutamate treatment, while ROS scavengers and ER chemical chaperones reduced Prx4 levels. Moreover, Prx4 overexpression reduces glutamate-induced apoptosis of HT22 cells by inhibiting ROS formation, Ca2+ influx, and ER stress. Therefore, we conclude that Prx4 has protective effects against glutamate-induced HT22 cell damage. Collectively, these results suggest that Prx4 could contribute to the treatment of neuronal disorders.
sj-docx-1-msj-10.1177_13524585211060326 – Supplemental material for Brighter spotty lesions on spinal MRI help differentiate AQP4 antibody-positive NMOSD from MOGAD
No full textSupplemental material, sj-docx-1-msj-10.1177_13524585211060326 for Brighter spotty lesions on spinal MRI help differentiate AQP4 antibody-positive NMOSD from MOGAD by Jae-Won Hyun, Hye Lim Lee, Jaehong Park, Jiah Kim, Ju-Hong Min, Byoung Joon Kim, Seung Woo Kim, Ha Young Shin, So-Young Huh, Woojun Kim, Ji Won Seo, Ki Hoon Kim, Su-Hyun Kim and Ho Jin Kim in Multiple Sclerosis Journal</p
EVOG: a database for evolutionary analysis of overlapping genes
No full textOverlapping genes are defined as a pair of genes whose transcripts are overlapped. Recently, many cases of overlapped genes have been investigated in various eukaryotic organisms; however, their origin and transcriptional control mechanism has not yet been clearly determined. In this study, we implemented evolutionary visualizer for overlapping genes (EVOG), a Web-based DB with a novel visualization interface, to investigate the evolutionary relationship between overlapping genes. Using this technique, we collected and analyzed all overlapping genes in human, chimpanzee, orangutan, marmoset, rhesus, cow, dog, mouse, rat, chicken, Xenopus, zebrafish and Drosophila. This integrated database provides a manually curated database that displays the evolutionary features of overlapping genes. The EVOG DB components included a number of overlapping genes (10074 in human, 10 009 in chimpanzee, 67 039 in orangutan, 51 001 in marmoset, 219 in rhesus, 3627 in cow, 209 in dog, 10 700 in mouse, 7987 in rat, 1439 in chicken, 597 in Xenopus, 2457 in zebrafish and 4115 in Drosophila). The EVOG database is very effective and easy to use for the analysis of the evolutionary process of overlapping genes when comparing different species. Therefore, EVOG could potentially be used as the main tool to investigate the evolution of the human genome in relation to disease by comparing the expression profiles of overlapping genes.open
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