• Title/Summary/Keyword: Stress granules

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Stress granules dynamics: benefits in cancer

  • Jeong In, Lee;Sim, Namkoong
    • BMB Reports
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    • v.55 no.12
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    • pp.577-586
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    • 2022
  • Stress granules (SGs) are stress-induced subcellular compartments, which carry out a particular function to cope with stress. These granules protect cells from stress-related damage and cell death through dynamic sequestration of numerous ribonucleoproteins (RNPs) and signaling proteins, thereby promoting cell survival under both physiological and pathological condition. During tumorigenesis, cancer cells are repeatedly exposed to diverse stress stimuli from the tumor microenvironment, and the dynamics of SGs is often modulated due to the alteration of gene expression patterns in cancer cells, leading to tumor progression as well as resistance to anticancer treatment. In this mini review, we provide a brief discussion about our current understanding of the fundamental roles of SGs during physiological stress and the effect of dysregulated SGs on cancer cell fitness and cancer therapy.

Mammalian RNA Granules

  • Jayabalan, Aravinth Kumar;Ohn, Takbum
    • Biomedical Science Letters
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    • v.20 no.1
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    • pp.1-7
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    • 2014
  • RNA granules such as Stress Granules (SG) and P-Bodies (PB) are aggregates of translationally stalled messenger ribonucleoprotein (mRNP) complexes induced by a wide range of stresses. Over the past decade, extensive studies described key components of RNA granules, their molecular interactions and signaling pathways require for their assembly and disassembly. However, researches defining their exact roles under stress conditions have not been performed so far, although several studies suggested their roles in neurodegenerative diseases recently. In this review, we provide an introduction about their basic properties, key components, and the dynamic nature for their assembly.

Oxidative stress causes Alu RNA accumulation via PIWIL4 sequestration into stress granules

  • Hwang, Yeo Eun;Baek, Yu Mi;Baek, Ahruem;Kim, Dong-Eun
    • BMB Reports
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    • v.52 no.3
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    • pp.196-201
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    • 2019
  • The Alu element, the most abundant transposable element, is transcribed to Alu RNA. We hypothesized that the PIWI protein regulates the expression of Alu RNA in retinal pigment epithelial (RPE) cells, where accumulated Alu RNA leads to macular degeneration. Alu transcription was induced in RPE cells treated with $H_2O_2$. At an early stage of oxidative stress, PIWIL4 was translocated into the nucleus; however, subsequently it was sequestered into cytoplasmic stress granules, resulting in the accumulation of Alu RNA. An elevated amount of Alu RNA was positively correlated with the disruption of the epithelial features of RPE via induction of mesenchymal transition. Therefore, we suggest that oxidative stress causes Alu RNA accumulation via PIWIL4 sequestration into the cytoplasmic stress granules.

Identification of Neuregulin-2 as a novel stress granule component

  • Kim, Jin Ah;Jayabalan, Aravinth Kumar;Kothandan, Vinoth Kumar;Mariappan, Ramesh;Kee, Younghoon;Ohn, Takbum
    • BMB Reports
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    • v.49 no.8
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    • pp.449-454
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    • 2016
  • Stress Granules (SGs) are microscopically visible, phase dense aggregates of translationally stalled messenger ribonucleoprotein (mRNP) complexes formed in response to distinct stress conditions. It is generally considered that SG formation is induced to protect cells from conditions of stress. The precise constituents of SGs and the mechanism through which SGs are dynamically regulated in response to stress are not completely understood. Hence, it is important to identify proteins which regulate SG assembly and disassembly. In the present study, we report Neuregulin-2 (NRG2) as a novel component of SGs; furthermore, depletion of NRG2 potently inhibits SG formation. We also demonstrate that NRG2 specifically localizes to SGs under various stress conditions. Knockdown of NRG2 has no effect on stress-induced polysome disassembly, suggesting that the component does not influence early step of SG formation. It was also observed that reduced expression of NRG2 led to marginal increase in cell survival under arsenite-induced stress.

Clinical Effectiveness of Ikgibohyeol-tang(Yìqìbǔxuè-tāng) and Deer Antler on Fatigue Symptoms and HRV Results in Outpatients at Korean Medical Hospital: A Retrospective Chart Review Study (익기보혈탕과 녹용 복용이 한방병원 외래 환자의 피로 증상과 심박변이도 결과에 미치는 영향: 후향적 차트 리뷰)

  • Won Jung Ha;Sang-Kwan Moon;Han-Gyul Lee;Seung-Yeon Cho;Seong-Uk Park;Woo-sang Jung;Jung-Mi Park;Chang-Nam Ko;Ki-Ho Cho;Seungwon Kwon
    • The Journal of Korean Medicine
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    • v.43 no.3
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    • pp.139-149
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    • 2022
  • Objectives: This study was designed to investigate the clinical effectiveness of Ikgibohyeol-tang(Yìqìbǔxuè-tāng) granules and Deer antler granules on fatigue symptoms. Methods: This is a 39-patient case series from a retrospective chart review of outpatients who were treated with Ikgibohyeol-tang granules and Deer antler granules at a Kyung Hee University Korean Medicine Hospital (Seoul) between 1st, January 2015 to 1st, August 2021. We reviewed the patients who complained of fatigue and analyzed changes in the degree of discomfort with fatigue and accompanying symptoms and HRV (Heart Rate Variability) score before and after treatment. Results: After taking Ikgibohyeol-tang granules and Deer antler granules, the degree of discomfort with fatigue and accompanying symptoms decreased significantly compared to before taking them. After treatment, Autonomic nervous system activity, Stress resistance, Heart Stability increased, and Stress index, Degree of fatigue decreased significantly. Conclusions: This study showed subjective symptoms and objective indicator (HRV score) were improved by taking Ikgibohyeol-tang granules and Deer antler granules.

Cellular Risk Assessment of Cells Exposed to Extremely Low Frequency Electromagnetic Fields (극저주파 자기장 노출에 의한 세포 유해성 평가)

  • Kang, Heungsik;Lee, Seongpyo;Noh, Myunggyu;Kim, Ki-Jung;Kim, Keekwang
    • Journal of Digital Convergence
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    • v.19 no.5
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    • pp.207-214
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    • 2021
  • Humans are environmentally exposed to various electromagnetic fields, but the evaluation of the harmfulness of electromagnetic field and the development of a system therefor are still incomplete. We aimed to develop a system for evaluating biohazard against electromagnetic fields, and to determine biohazard through the system. An extremely-low frequency magnetic field generator was designed and manufactured, and the output reliability of the device was verified. Using this device, the effect on the formation of cellular stress-granules and the cell cycle progression of cells exposed to high magnetic fields of 6 mT and 60 Hz was confirmed. As a result, exposure to high magnetic fields of 6 hr, 12 hr and 36 hr did not affect the formation of cell stress-induced granules and the cell division cycle. These results are an important basis for the determination of biohazard to the extremely-low frequency high magnetic field.

Lipofuscin Granule Accumulation Requires Autophagy Activation

  • Seon Beom Song;Woosung Shim;Eun Seong Hwang
    • Molecules and Cells
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    • v.46 no.8
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    • pp.486-495
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    • 2023
  • Lipofuscins are oxidized lipid and protein complexes that accumulate during cellular senescence and tissue aging, regarded as markers for cellular oxidative damage, tissue aging, and certain aging-associated diseases. Therefore, understanding their cellular biological properties is crucial for effective treatment development. Through traditional microscopy, lipofuscins are readily observed as fluorescent granules thought to accumulate in lysosomes. However, lipofuscin granule formation and accumulation in senescent cells are poorly understood. Thus, this study examined lipofuscin accumulation in human fibroblasts exposed to various stressors. Our results substantiate that in glucose-starved or replicative senescence cells, where elevated oxidative stress levels activate autophagy, lipofuscins predominately appear as granules that co-localize with autolysosomes due to lysosomal acidity or impairment. Meanwhile, autophagosome formation is attenuated in cells experiencing oxidative stress induced by a doxorubicin pulse and chase, and lipofuscin fluorescence granules seldom manifest in the cytoplasm. As Torin-1 treatment activates autophagy, granular lipofuscins intensify and dominate, indicating that autophagy activation triggers their accumulation. Our results suggest that high oxidative stress activates autophagy but fails in lipofuscin removal, leaving an abundance of lipofuscin-filled impaired autolysosomes, referred to as residual bodies. Therefore, future endeavors in treating lipofuscin pathology-associated diseases and dysfunctions through autophagy activation demand meticulous consideration.

Stress Granules Inhibit Coxsackievirus B3-Mediated Cell Death via Reduction of Mitochondrial Reactive Oxygen Species and Viral Extracellular Release

  • Ji-Ye Park;Ok Sarah Shin
    • Journal of Microbiology and Biotechnology
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    • v.33 no.5
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    • pp.582-590
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    • 2023
  • Stress granules (SGs) are cytoplasmic aggregates of RNA-protein complexes that form in response to various cellular stresses and are known to restrict viral access to host translational machinery. However, the underlying molecular mechanisms of SGs during viral infections require further exploration. In this study, we evaluated the effect of SG formation on cellular responses to coxsackievirus B3 (CVB3) infection. Sodium arsenite (AS)-mediated SG formation suppressed cell death induced by tumor necrosis factor-alpha (TNF-a)/cycloheximide (CHX) treatment in HeLa cells, during which G3BP1, an essential SG component, contributed to the modulation of apoptosis pathways. SG formation in response to AS treatment blocked CVB3-mediated cell death, possibly via the reduction of mitochondrial reactive oxygen species. Furthermore, we examined whether AS treatment would affect small extracellular vesicle (sEV) formation and secretion during CVB3 infection and modulate human monocytic cell (THP-1) response. CVB3-enriched sEVs isolated from HeLa cells were able to infect and replicate THP-1 cells without causing cytotoxicity. Interestingly, sEVs from AS-treated HeLa cells inhibited CVB3 replication in THP-1 cells. These findings suggest that SG formation during CVB3 infection modulates cellular response by inhibiting the release of CVB3-enriched sEVs.

Fabrication and Characterization of Zirconia Thermal Barrier Coatings by Spray Drying and Atmospheric Plasma Spraying (분무건조 및 대기 플라즈마 용사에 의한 지르코니아 열차폐 코팅재의 제조 및 평가)

  • Kim, Chul;Heo, Yong Suk;Kim, Tae Woo;Lee, Kee Sung
    • Journal of the Korean Ceramic Society
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    • v.50 no.5
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    • pp.326-332
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    • 2013
  • In this study, we prepared yttria stabilized zirconia granules for thermal barrier coatings using a spray drying process. First, we characterized the properties of granules such as flow rate and packing density for utilizing the air plasma spray process. The flow rate and packing density data showed 0.732 g/sec and 2.14 $g/cm^3$, respectively, when we used larger and denser particles, which are better than hollow granules or smaller spherical granules. Second, we chose larger, spherical granules fabricated in alcohol solvent as starting powders and sprayed it on the bondcoat/nimonic alloy by an atmospheric plasma spray process varying the process parameters, the feeding rate, gun speed and spray distance. Finally, we evaluated representative thermal and mechanical characteristics. The thermal expansion coefficients of the coatings were $11{\sim}12.7{\times}10^{-6}/^{\circ}C$ and the indentation stress measured was 2.5 GPa at 0.15 of indentation strain.

PB-Overexpression of OsZn15, a CCCH-tandem zinc finger protein, increases drought tolerance in rice

  • Seong, So Yoon;Jung, Harin;Choi, Yang Do;Kim, Ju-Kon
    • Proceedings of the Korean Society of Crop Science Conference
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    • 2017.06a
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    • pp.115-115
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    • 2017
  • Zinc finger proteins constitute a large family which has been studied to have various functions in different organisms. Tandem CCCH zinc finger proteins (TZFs), members of the zinc finger protein family, are known to participate as post-transcriptional regulators of gene expression in eukaryotes. Here, we showed that the OsZn15, a gene for tandem CCCH zinc finger protein, is induced by abiotic stress and its overexpression in transgenic rice plants (PGD1:OsZn15) gains higher drought tolerance. Gene expression analysis of promoter:GFP plants revealed that OsZn15 is specifically expressed in anther and embryo, but not in vegetative organs. In-field evaluation, grain yield was higher in the PGD1:OsZn15 than nontransgenic plants under drought conditions. Interestingly, OsZn15 is shown to not only localize at nucleus but also co-localize with both processing bodies (PB) and stress granules (SG), two messenger ribo-nucleoprotein complexes which are known to activate by forming cytoplasmic foci under stress conditions. In sum, these results suggest that OsZn15 increases drought stress tolerance of rice probably by participating in RNA turnover in PB and SG.

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