• 제목/요약/키워드: Translational research

검색결과 533건 처리시간 0.035초

Anisomycin protects against sepsis by attenuating IκB kinase-dependent NF-κB activation and inflammatory gene expression

  • Park, Gyoung Lim;Park, Minkyung;Min, Jeong-Ki;Park, Young-Jun;Chung, Su Wol;Lee, Seon-Jin
    • BMB Reports
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    • 제54권11호
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    • pp.545-550
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    • 2021
  • Anisomycin is known to inhibit eukaryotic protein synthesis and has been established as an antibiotic and anticancer drug. However, the molecular targets of anisomycin and its mechanism of action have not been explained in macrophages. Here, we demonstrated the anti-inflammatory effects of anisomycin both in vivo and in vitro. We found that anisomycin decreased the mortality rate of macrophages in cecal ligation and puncture (CLP)- and lipopolysaccharide (LPS)-induced acute sepsis. It also declined the gene expression of proinflammatory mediators such as inducible nitric oxide synthase, tumor necrosis factor-α, and interleukin-1β as well as the nitric oxide and proinflammatory cytokines production in macrophages subjected to LPS-induced acute sepsis. Furthermore, anisomycin attenuated nuclear factor (NF)-κB activation in LPS-induced macrophages, which correlated with the inhibition of phosphorylation of NF-κB-inducing kinase and IκB kinase, phosphorylation and IκBα proteolytic degradation, and NF-κB p65 subunit nuclear translocation. These results suggest that anisomycin prevented acute inflammation by inhibiting NF-κB-related inflammatory gene expression and could be a potential therapeutic candidate for sepsis.

Histone Modifications During DNA Replication

  • Falbo, Karina B.;Shen, Xuetong
    • Molecules and Cells
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    • 제28권3호
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    • pp.149-154
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    • 2009
  • Faithful and accurate replication of the DNA molecule is essential for eukaryote organisms. Nonetheless, in the last few years it has become evident that inheritance of the chromatin states associated with different regions of the genome is as important as the faithful inheritance of the DNA sequence itself. Such chromatin states are determined by a multitude of factors that act to modify not only the DNA molecule, but also the histone proteins associated with it. For instance, histones can be posttranslationally modified, and it is well established that these posttranslational marks are involved in several essential nuclear processes such as transcription and DNA repair. However, recent evidence indicates that posttranslational modifications of histones might be relevant during DNA replication. Hence, the aim of this review is to describe the most recent publications related to the role of histone posttranslational modifications during DNA replication.

Deubiquitinase USP35 as a novel mitotic regulator via maintenance of Aurora B stability

  • Park, Jinyoung;Song, Eun Joo
    • BMB Reports
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    • 제51권6호
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    • pp.261-262
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    • 2018
  • Aurora B is an important kinase involved in dynamic cellular events in mitosis. Aurora B activity is controlled by several post-translational modifications (PTMs). Among them, E3 ubiquitin ligase-mediated ubiquitination plays crucial roles in controlling the relocation and degradation of Aurora B. Aurora B, ubiquitinated by different E3 ligases, moves to the exact site for its mitotic function during metaphase-anaphase transition and is then degraded for cell cycle progression at the end of mitosis. However, how the stability of Aurora B is maintained until its degradation has been poorly understood. Recently, we have found that USP35 acts as a deubiquitinating enzyme (DUB) for Aurora B and affects its stability during cell division, thus being involved in the regulation of mitosis. In this review, we discuss the USP35-mediated deubiquitination of Aurora B and the regulation of mitotic progression by USP35.

PET 리포터 유전자를 이용한 이행성 연구 (Translational Imaging with PET Reporter Gene Approaches)

  • 민정준
    • Nuclear Medicine and Molecular Imaging
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    • 제40권6호
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    • pp.279-292
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    • 2006
  • Recent progress in the development of non-invasive imaging technologies continues to strengthen the role of biomedical research. These tools have been validated recently in variety of research models, and have born shown to provide continuous quantitative monitoring of the location(s), magnitude, and time-variation of gene delivery and/or expression. This article reviews the use of PET technologies as they have been used in imaging biological processes for molecular imaging applications. The studies published to date demonstrate that noninvasive imaging tools will help to accelerate pre-clinical model validation as well as allow for clinical monitoring of human diseases.

Euglena의 Cytochrome C552 Methylation에 관한 연구 (Studies on the possible existence of methylarginine in cytochrome C552 isolated from Euglena gracilis)

  • 이향우;백운기
    • 약학회지
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    • 제32권6호
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    • pp.420-427
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    • 1988
  • Post-translational modification of protein amino acid residues is a well known metabolic phenomenon. One such side chain modification, protein methylation, occur ubiquitously in nature, in organism ranging from prokaryotic to eukaryotic and the biological significance of protein methylation has begun to emerge. The observation that cytochrome C methylation facilitates the binding of this hemoprotein to mitochondria could be placed as the one of the examples along this line. However, the detail biological meaning of cytochrome C methylation is remained to be clarified. In the aspect of such reason this research was done. The results of this experiment were; 1) pure Euglena gracilis cytochrome C552 was isolated, 2) methylarginine and methylmethionine were not found in cytochrome C552 sequence, 3) however, Unknown Peak at 20.78min of retention time was found, and 4) this Unknown Peak was found only from Euglena cytochrome C552, so far.

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An experimental approach to study the function of mitochondria in cardiomyopathy

  • Chung, Youn Wook;Kang, Seok-Min
    • BMB Reports
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    • 제48권10호
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    • pp.541-548
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    • 2015
  • Cardiomyopathy is an inherited or acquired disease of the myocardium, which can result in severe ventricular dysfunction. Mitochondrial dysfunction is involved in the pathological process of cardiomyopathy. Many dysfunctions in cardiac mitochondria are consequences of mutations in nuclear or mitochondrial DNA followed by alterations in transcriptional regulation, mitochondrial protein function, and mitochondrial dynamics and energetics, presenting with associated multisystem mitochondrial disorders. To ensure correct diagnosis and optimal management of mitochondrial dysfunction in cardiomyopathy caused by multiple pathogenesis, multidisciplinary approaches are required, and to integrate between clinical and basic sciences, ideal translational models are needed. In this review, we will focus on experimental models to provide insights into basic mitochondrial physiology and detailed underlying mechanisms of cardiomyopathy and current mitochondria-targeted therapies for cardiomyopathy.

고등식물의 유전자 발현의 조절 (Regulation of Gene Expression in Higher Plant)

  • 심웅섭
    • 한국식물학회:학술대회논문집
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    • 한국식물학회 1987년도 식물생명공학 심포지움 논문집 Proceedings of Symposia on Plant Biotechnology
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    • pp.241-260
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    • 1987
  • The regulatory mechanisms of gene expression in higher plant were not ascertained in detail because the genome size is very large and complex. However, the above-mentioned study is remarkably progressed in parallel with development of DNA recombinant technology and plant vector system. Some research results connected with the mechanisms could be summarized as follows. 1. Many plant genes including chloroplast genes are cloned. 2. The structures of some regulatory regions of gene expression are determined, and it is confirmed that new regulatory units are made by transposable elements. 3. Plant gene expression is regulated not only at transcriptional level but also at translational level. 4. The factors that regulate plant gene expression could be divided as two categorys. One is endogenous elements including the structural change of chromatin during development stage and tissue differentiation. The other is environmental stimulations such as air, water, heat, salts and light. However, some sufficient research-aid fund is essential in order to study the regulatory mechanisms of gene expression more systematically.

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Seismic behavior of strengthened reinforced concrete coupling beams by bolted steel plates, Part 1: Experimental study

  • Zhu, Y.;Su, R.K.L.;Zhou, F.L.
    • Structural Engineering and Mechanics
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    • 제27권2호
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    • pp.149-172
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    • 2007
  • An experimental study of five full-scale coupling beam specimens has been conducted to investigate the seismic behavior of strengthened RC coupling beams by bolted side steel plates using a reversed cyclic loading procedure. The strengthened coupling beams are fabricated with different plate thicknesses and shear connector arrangements to study their respective effects on load-carrying capacity, strength retention, stiffness degradation, deformation capacity, and energy dissipation ability. The study revealed that putting shear connectors along the span of coupling beams produces no significant improvement to the structural performance of the strengthened beams. Translational and rotational partial interactions of the shear connectors that would weaken the load-carrying capacity of the steel plates were observed and measured. The hierarchy of failure of concrete, steel plates, and shear connectors was identified. Furthermore, detailed effects of plate buckling and various arrangements of shear connectors on the post-peak behavior of the strengthened beams are discussed.

Investigation of the Relationship between Protein, Message and Inducer Concentrations in Recombinant E. coli Cells

  • Jorgensen, Lene;Connor J. Thomas;Brian K. Oneill;Anton P.J. Middelbeg
    • Journal of Microbiology and Biotechnology
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    • 제7권1호
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    • pp.21-24
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    • 1997
  • Chloramphenicol acetyl transferase (CAT) protein and mRNA levels in E. coli were determined following induction of a tac::cat construct by isopropyl-${\beta}$-thiogalactopyranoside (IPTG). High cat mRNA levels did not directly reflect CAT protein levels, in either shakeflask experiments or fermentations. Furthermore, concentrations of IPTG resulting in the highest levels of expression of cat mRNA, were different to those resulting in highest levels of CAT protein. The data suggest that high transcriptional activities lead to limitations at the translational level.

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Peroxiredoxins and the Regulation of Cell Death

  • Hampton, Mark B.;O'Connor, Karina M.
    • Molecules and Cells
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    • 제39권1호
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    • pp.72-76
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    • 2016
  • Cell death pathways such as apoptosis can be activated in response to oxidative stress, enabling the disposal of damaged cells. In contrast, controlled intracellular redox events are proposed to be a significant event during apoptosis signaling, regardless of the initiating stimulus. In this scenario oxidants act as second messengers, mediating the post-translational modification of specific regulatory proteins. The exact mechanism of this signaling is unclear, but increased understanding offers the potential to promote or inhibit apoptosis through modulating the redox environment of cells. Peroxiredoxins are thiol peroxidases that remove hydroperoxides, and are also emerging as important players in cellular redox signaling. This review discusses the potential role of peroxiredoxins in the regulation of apoptosis, and also their ability to act as biomarkers of redox changes during the initiation and progression of cell death.