• Title/Summary/Keyword: Integrated Stress Response

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Two distinct nodes of translational inhibition in the Integrated Stress Response

  • Ryoo, Hyung Don;Vasudevan, Deepika
    • BMB Reports
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    • v.50 no.11
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    • pp.539-545
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    • 2017
  • The Integrated Stress Response (ISR) refers to a signaling pathway initiated by stress-activated $eIF2{\alpha}$ kinases. Once activated, the pathway causes attenuation of global mRNA translation while also paradoxically inducing stress response gene expression. A detailed analysis of this pathway has helped us better understand how stressed cells coordinate gene expression at translational and transcriptional levels. The translational attenuation associated with this pathway has been largely attributed to the phosphorylation of the translational initiation factor $eIF2{\alpha}$. However, independent studies are now pointing to a second translational regulation step involving a downstream ISR target, 4E-BP, in the inhibition of eIF4E and specifically cap-dependent translation. The activation of 4E-BP is consistent with previous reports implicating the roles of 4E-BP resistant, Internal Ribosome Entry Site (IRES) dependent translation in ISR active cells. In this review, we provide an overview of the translation inhibition mechanisms engaged by the ISR and how they impact the translation of stress response genes.

The trinity of ribosome-associated quality control and stress signaling for proteostasis and neuronal physiology

  • Park, Jumin;Park, Jongmin;Lee, Jongbin;Lim, Chunghun
    • BMB Reports
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    • v.54 no.9
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    • pp.439-450
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    • 2021
  • Translating ribosomes accompany co-translational regulation of nascent polypeptide chains, including subcellular targeting, protein folding, and covalent modifications. Ribosome-associated quality control (RQC) is a co-translational surveillance mechanism triggered by ribosomal collisions, an indication of atypical translation. The ribosome-associated E3 ligase ZNF598 ubiquitinates small subunit proteins at the stalled ribosomes. A series of RQC factors are then recruited to dissociate and triage aberrant translation intermediates. Regulatory ribosomal stalling may occur on endogenous transcripts for quality gene expression, whereas ribosomal collisions are more globally induced by ribotoxic stressors such as translation inhibitors, ribotoxins, and UV radiation. The latter are sensed by ribosome-associated kinases GCN2 and ZAKα, activating integrated stress response (ISR) and ribotoxic stress response (RSR), respectively. Hierarchical crosstalks among RQC, ISR, and RSR pathways are readily detectable since the collided ribosome is their common substrate for activation. Given the strong implications of RQC factors in neuronal physiology and neurological disorders, the interplay between RQC and ribosome-associated stress signaling may sustain proteostasis, adaptively determine cell fate, and contribute to neural pathogenesis. The elucidation of underlying molecular principles in relevant human diseases should thus provide unexplored therapeutic opportunities.

Comparison of Growth Performance and Stress Response between Male and Female Korean Native Commercial Chickens (토종실용닭의 암수 간 산육 능력 및 스트레스 반응 정도 비교)

  • Sohn, Sea Hwan;Cho, Eun Jung;Kim, Ki Gon;Shin, Ka Bin;Lee, Seul Gy
    • Korean Journal of Poultry Science
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    • v.49 no.2
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    • pp.89-98
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    • 2022
  • This study compared the production and physiological characteristics of male and female Korean native commercial chickens. We investigated the growth performance, vitality, and stress response of 479 male and 608 female chickens from 1 d to 12 weeks of age. The body weight, feed consumption and feed conversion ratio were measured as growth performance. The survival rate, amount of telomeric DNA, DNA damage rate, heterophil-lymphocyte ratio (H/L ratio), and heat shock protein (HSP)-70, HSP-90α, and HSP-90β gene expression levels were analyzed as indicators of vitality and stress response. Body weight was significantly higher in male chickens than in female chickens after 2 weeks of age (P<0.01). Feed intake was higher in male chickens than in female chickens, whereas the feed conversion ratio showed the opposite trend. The survival rate was significantly higher in female chickens than in male chickens (82.8% vs. 73.8%, P<0.05). Stress response analysis revealed no differences between male and female chickens in terms of telomeric DNA content, DNA damage rate, H/L ratio, and HSP gene expression levels. Taken together, it was concluded that there was a significant difference in the growth performance and survival rate between male and female Korean native commercial chickens, whereas there was no difference in the degree of stress response between them. Therefore, in terms of the productivity of Korean native commercial chickens, it is judged that separate-sex rearing is much more advantageous than mixed rearing, regardless of the physiological characteristics of males and females.

A Study of Depression, Anxiety, Stress Response and Self-care by Gender in Diabetic Patients (당뇨병 환자의 성별 우울, 불안, 스트레스 반응과 자가관리의 관계연구)

  • Song, Min-Sun;Cho, Young-Im
    • The Korean Journal of Rehabilitation Nursing
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    • v.9 no.2
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    • pp.145-152
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    • 2006
  • Purpose: The purpose of this study was to investigate the depression, anxiety, stress response and self-care, to analyze the correlation among depression, anxiety, stress response and self-care by gender, and to determine factors associated with self-care in diabetic patients. Method: The subjects of this study were 103 participants with diabetes mellitus. Data were analyzed by chi-square test, t-test, Pearson correlation coefficient and multiple regression analysis by using SAS program. Result: Items for self-care evaluation by gender were significant differences in hospital visit, hypoglycemia preparation, proper hygiene, taking a rest, foot injury check, drinking, and smoking. The female patients are more likely to have higher self-care score than the male patients. However, there were no differences in depression, anxiety and stress response by gender. In male patients, there were positive correlations between the degree of depression and stress response, the degree of anxiety and stress response. In female patients, there were positive correlations between the degree of depression and stress response, the degree of anxiety and stress response. In multiple regression analysis, gender and experienced admission is associated with self-care. Conclusion: We should consider integrated approaches for psychological problems in the management of diabetic patients.

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Antioxidant Systems of Plant Pathogenic Fungi: Functions in Oxidative Stress Response and Their Regulatory Mechanisms

  • Jiyeun Park;Hokyoung Son
    • The Plant Pathology Journal
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    • v.40 no.3
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    • pp.235-250
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    • 2024
  • During the infection process, plant pathogenic fungi encounter plant-derived oxidative stress, and an appropriate response to this stress is crucial to their survival and establishment of the disease. Plant pathogenic fungi have evolved several mechanisms to eliminate oxidants from the external environment and maintain cellular redox homeostasis. When oxidative stress is perceived, various signaling transduction pathways are triggered and activate the downstream genes responsible for the oxidative stress response. Despite extensive research on antioxidant systems and their regulatory mechanisms in plant pathogenic fungi, the specific functions of individual antioxidants and their impacts on pathogenicity have not recently been systematically summarized. Therefore, our objective is to consolidate previous research on the antioxidant systems of plant pathogenic fungi. In this review, we explore the plant immune responses during fungal infection, with a focus on the generation and function of reactive oxygen species. Furthermore, we delve into the three antioxidant systems, summarizing their functions and regulatory mechanisms involved in oxidative stress response. This comprehensive review provides an integrated overview of the antioxidant mechanisms within plant pathogenic fungi, revealing how the oxidative stress response contributes to their pathogenicity.

Targeting the Osmotic Stress Response for Strain Improvement of an Industrial Producer of Secondary Metabolites

  • Godinez, Octavio;Dyson, Paul;del Sol, Ricardo;Barrios-Gonzalez, Javier;Millan-Pacheco, Cesar;Mejia, Armando
    • Journal of Microbiology and Biotechnology
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    • v.25 no.11
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    • pp.1787-1795
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    • 2015
  • The transition from primary to secondary metabolism in antibiotic-producing Streptomyces correlates with expression of genes involved in stress responses. Consequently, regulatory pathways that regulate specific stress responses are potential targets to manipulate to increase antibiotic titers. In this study, genes encoding key proteins involved in regulation of the osmotic stress response in Streptomyces avermitilis, the industrial producer of avermectins, are investigated as targets. Disruption of either osaBSa, encoding a response regulator protein, or osaCSa, encoding a multidomain regulator of the alternative sigma factor SigB, led to increased production of both oligomycin, by up to 200%, and avermectin, by up to 37%. The mutations also conditionally affected morphological development; under osmotic stress, the mutants were unable to erect an aerial mycelium. In addition, we demonstrate the delivery of DNA into a streptomycete using biolistics. The data reveal that information on stress regulatory responses can be integrated in rational strain improvement to improve yields of bioactive secondary metabolites.

Involvement of Caenohabditis elegans MAPK Signaling Pathways in Oxidative Stress Response Induced by Silver Nanoparticles Exposure

  • Roh, Ji-Yeon;Eom, Hyun-Jeong;Choi, Jin-Hee
    • Toxicological Research
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    • v.28 no.1
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    • pp.19-24
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    • 2012
  • In the present study, toxicity of silver nanoparticles (AgNPs) was investigated in the nematode, Caenohabditis elegans focusing on the upstream signaling pathway responsible for regulating oxidative stress, such as mitogen-activated protein kinase (MAPK) cascades. Formation of reactive oxygen species (ROS) was observed in AgNPs exposed C.elegans, suggesting oxidative stress as an important mechanism in the toxicity of AgNPs towards C. elegans. Expression of genes in MAPK signaling pathways increased by AgNPs exposure in less than 2-fold compared to the control in wildtype C.elegans, however, those were increased dramatically in sod-3 (gk235) mutant after 48 h exposure of AgNPs (i.e. 4-fold for jnk-1 and mpk-2; 6-fold for nsy-1, sek-1, and pmk-1, and 10-fold for jkk-1). These results on the expression of oxidative stress response genes suggest that sod-3 gene expression appears to be dependent on p38 MAPK activation. The high expressions of the pmk-1 gene 48 h exposure to AgNPs in the sod-3 (gk235) mutant can also be interpreted as compensatory mechanisms in the absence of important stress response genes. Overall results suggest that MAPK-based integrated stress signaling network seems to be involved in defense to AgNPs exposure in C.elegans.

Genotoxicity Assay Using Chromosomally-Integrated Bacterial recA::Lux

  • Min, Ji-Ho;Gu, Man-Bock
    • Journal of Microbiology and Biotechnology
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    • v.13 no.1
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    • pp.99-103
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    • 2003
  • An Escherichia coli strain containing the recA promoter that fused to the luxCDABE operon originating from Photorhabdus luminescens was shown to respond sensitively to genotoxic stresses. Two different recombinant bacteria, one (DPDI 657) harboring a plasmid with the recA promoter that fused to the luxCDABE operon, and the other (DPD1710) containing a chromosomally-integrated recA promoter that fused with luxCDABE, were compared and it was found that the sensitivity of 'the two strains was significantly different in terms of their bioluminescent level, response time, and the minimum detectable concentration of a chemical causing DNA damaging stress. DPDI 710, with a chromosomally-integrated single copy, generally led to lower basal luminescence levels, faster responses, increased response ratios, and an enhanced sensitivity to mutagens, when compared to DPD 1657 with a multi-copy plasmid.

Validation of exercise-response genes in skeletal muscle cells of Thoroughbred racing horses

  • Kim, Doh Hoon;Lee, Hyo Gun;Sp, Nipin;Kang, Dong Young;Jang, Kyoung-Jin;Lee, Hak Kyo;Cho, Byung-Wook;Yang, Young Mok
    • Animal Bioscience
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    • v.34 no.1
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    • pp.134-142
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    • 2021
  • Objective: To understand the athletic characteristics of Thoroughbreds, high-throughput analysis has been conducted using horse muscle tissue. However, an in vitro system has been lacking for studying and validating genes from in silico data. The aim of this study is to validate genes from differentially expressed genes (DEGs) of our previous RNA-sequencing data in vitro. Also, we investigated the effects of exercise-induced stress including heat, oxidative, hypoxic and cortisol stress on horse skeletal muscle derived cells with the top six upregulated genes of DEGs. Methods: Enriched pathway analysis was conducted using the Database for Annotation, Visualization, and Integrated Discovery (DAVID) tool with upregulated genes in horse skeletal muscle tissue after exercise. Among the candidates, the top six genes were analysed through geneMANIA to investigate gene networks. Muscle cells derived from neonatal horse skeletal tissue were maintained and subjected to exercise-related stressors. Transcriptional changes in the top six genes followed by stressors were investigated using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Results: The inflammation response pathway was the most commonly upregulated pathway after horse exercise. Under non-cytotoxic conditions of exercise-related stressors, the transcriptional response of the top six genes was different among types of stress. Oxidative stress yielded the most similar expression pattern to DEGs. Conclusion: Our results indicate that transcriptional change after horse exercise in skeletal muscle tissue strongly relates to stress response. The qRT-PCR results showed that stressors contribute differently to the transcriptional regulation. These results would be valuable information to understand horse exercise in the stress aspect.

The Virulence of Vibrio vulnificus is Affected by the Cellular Level of Superoxide Dismutase Activity

  • Kang, In-Hye;Kim, Ju-Sim;Lee, Jeong-K.
    • Journal of Microbiology and Biotechnology
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    • v.17 no.8
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    • pp.1399-1402
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    • 2007
  • The virulence of superoxide dismutase (SOD) mutants of Vibrio vulnificus, as tested by intraperitoneal injection into mice, decreases in the order of sodC mutant, sodA mutant, and sodB mutant lacking CuZnSOD, MnSOD, and FeSOD, respectively. The survival of SOD mutants under superoxide stress also decreases in the same order. The virulence of soxR mutant, which is unable to induce MnSOD in response to superoxide, is similar to that of the sodA mutant, as the survival of the soxR mutant under superoxide stress is similar to that of the sodA mutant. Consistently, the lowered survival of the soxR mutant is complemented not only with soxR but also with sodA. Thus, the virulence of V. vulnificus is significantly affected by the cellular level of SOD activity, and an increase in SOD level through MnSOD induction by SoxR under superoxide stress is essential for virulence.