• Molecules and Cells
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• 제41권1호
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• pp.35-44
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• 2018

Mitochondria are responsible for supplying of most of the cell's energy via oxidative phosphorylation. However, mitochondria also can be deleterious for a cell because they are the primary source of reactive oxygen species, which are generated as a byproduct of respiration. Accumulation of mitochondrial and cellular oxidative damage leads to diverse pathologies. Thus, it is important to maintain a population of healthy and functional mitochondria for normal cellular metabolism. Eukaryotes have developed defense mechanisms to cope with aberrant mitochondria. Mitochondria autophagy (known as mitophagy) is thought to be one such process that selectively sequesters dysfunctional or excess mitochondria within double-membrane autophagosomes and carries them into lysosomes/vacuoles for degradation. The power of genetics and conservation of fundamental cellular processes among eukaryotes make yeast an excellent model for understanding the general mechanisms, regulation, and function of mitophagy. In budding yeast, a mitochondrial surface protein, Atg32, serves as a mitochondrial receptor for selective autophagy that interacts with Atg11, an adaptor protein for selective types of autophagy, and Atg8, a ubiquitin-like protein localized to the isolation membrane. Atg32 is regulated transcriptionally and post-translationally to control mitophagy. Moreover, because Atg32 is a mitophagy-specific protein, analysis of its deficient mutant enables investigation of the physiological roles of mitophagy. Here, we review recent progress in the understanding of the molecular mechanisms and functional importance of mitophagy in yeast at multiple levels.

• Journal of Nutrition and Health
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• 제29권2호
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• pp.159-165
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• 1996

This study was performed to investigate the effects of concentration and degree of unsaturation of fatty acids on cellular proliferation and lipid peroxide production, using primary skin fibroblasts from neonate rats Fibroblasts (CPD : 2.8-5.4). Cells were cultured either in control medium (Dulbecco's modified Eagle's medium supplement with 10% fetal bovine serum) or in media supplemented with various kinds (stearic, oleic, linoleic, arachidonic, linolenic, eicosapentaenoic acid) and amounts (5, 10, 25, 50, 100, 150uM)of fatty acids. Cellular proliferation ratio and lipid peroxice production were measured and morphological changes were observed. Cellular proliferation was inhibited and morphological changes were observed. Cellular proliferation was inhibited and morphological changes were observed in cells grown in stearic containing media. Oleic, arachidonic, and eicosapentaenoic aicd tend to stimulate cellualar proliferation, and linolenic acid had no effects. Lipid peroxide concentrations in fibroblasts increased in proportion to the contents and unsaturation of fatty acids in media. Especially supplementation of arachidonic acid accelerated cellualr lipid peroxidation. Free radicals may cause severs damage to biological molecules, so lipid peroxidation probably contributes cellular membrane damages. However there were little relationship between lipid peroxide production and cellular proliferation in this study. (Korean J Nutrition 29(2) : 159~165, 1996)

• BMB Reports
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• 제52권1호
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• pp.24-34
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• 2019

Sirtuin is an essential factor that delays cellular senescence and extends the organismal lifespan through the regulation of diverse cellular processes. Suppression of cellular senescence by Sirtuin is mainly mediated through delaying the age-related telomere attrition, sustaining genome integrity and promotion of DNA damage repair. In addition, Sirtuin modulates the organismal lifespan by interacting with several lifespan regulating signaling pathways including insulin/IGF-1 signaling pathway, AMP-activated protein kinase, and forkhead box O. Although still controversial, it is suggested that the prolongevity effect of Sirtuin is dependent with the level of and with the tissue expression of Sirtuin. Since Sirtuin is also believed to mediate the prolongevity effect of calorie restriction, activators of Sirtuin have attracted the attention of researchers to develop therapeutics for age-related diseases. Resveratrol, a phytochemical rich in the skin of red grapes and wine, has been actively investigated to activate Sirtuin activity with consequent beneficial effects on aging. This article reviews the evidences and controversies regarding the roles of Sirtuin on cellular senescence and lifespan extension, and summarizes the activators of Sirtuin including Sirtuin-activating compounds and compounds that increase the cellular level of nicotinamide dinucleotide.

• Molecules and Cells
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• 제25권4호
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• pp.457-461
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• 2008

DNA damage checkpoint is an important self-defense mechanism for the maintenance of genome stability. Defects in DNA damage signaling and repair lead to various disorders and increase tumor incidence in humans. In the past 10 years, we have identified many components involved in the DNA damage-signaling pathway, including the product of breast cancer susceptibility gene 1 (BRCA1). Mutations in BRCA1 are associated with increased risk of breast and ovarian cancers, highlighting the importance of this DNA damage-signaling pathway in tumor suppression. While it becomes clear that BRCA1 plays a crucial role in the DNA damage responsive pathway, exactly how BRCA1 receives DNA damage signals and exerts its checkpoint function has not been fully addressed. A series of recent studies reported the discovery of many novel components involved in DNA damage-signaling pathway. These newly identified checkpoint proteins, including RNF8, RAP80 and CCDC98, work in concern in recruiting BRCA1 to DNA damage sites and thus regulate BRCA1 function in G2/M checkpoint control. This review will summarize these recent findings and provide an updated view of the regulation of BRCA1 in response to DNA damage.

• Geomechanics and Engineering
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• 제36권2호
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• pp.121-130
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• 2024

Many foundation projects are built on red-bed soft rocks, and the damage evolution of this kind of rocks affects the safety of these projects. At present, there is insufficient research on the damage evolution of red-bed soft rocks, especially the progressive process from mesoscopic texture change to macroscopic elastoplastic deformation. Therefore, based on the dual-porosity characteristics of pores and fissures in soft rock, we adopted a cellular automata model to simulate the propagation of these voids in soft rocks under an external load. Further, we established a macro-mesoscopic damage model of red-bed soft rocks, and its reliability was verified by tests. The results indicate that the relationship between the number and voids size conformed to a quartic polynomial, whereas the relationship between the damage variable and damage porosity conformed to a logistic curve. The damage porosity was affected by dual-porosity parameters such as the fractal dimension of pores and fissures. We verified the reliability of the model by comparing the test results with an established damage model. Our research results described the progressive process from mesoscopic texture change to macroscopic elastoplastic deformation and provided a theoretical basis for the damage evolution of these rocks.

• Molecules and Cells
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• 제26권4호
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• pp.350-355
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• 2008

Chk2 is a well characterized protein kinase with key roles in the DNA damage response. Chk2 is activated by phosphorylation following DNA damage, and relays that signal to various substrate proteins to induce cell cycle arrest, DNA repair, and apoptosis. In order to identify novel components of the Chk2 signaling pathway in Drosophila, we screened 2,240 EP misexpression lines for dominant modifiers of an adult rough eye phenotype caused by Chk2 overexpression in postmitotic cells of the eye imaginal disc. The rough eye phenotype was suppressed by mutation of the ATM kinase, a well-described activator of Chk2. Twenty-five EP modifiers were identified (three enhancers and 22 suppressors), none of which correspond to previously known components of Chk2 signaling. Three EPs caused defects in G2 arrest after irradiation with incomplete penetrance when homozygous, and are likely directly involved in the response to DNA damage. Possible roles for these modifiers in the DNA damage response and Chk2 signaling are discussed.

• Journal of Nutrition and Health
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• 제36권6호
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• pp.570-576
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• 2003

스트레스에 의해서 생체는 에너지 대사를 증가시키며, 에너지 대사의 증가는 높은 반응성의 ROS를 생성한다. ROS는 높은 반응성으로 인해 지질, 단백질 등을 과산화시켜 원래의 활성을 잃게 한다. 이런 ROS에 대해서 높은 소거능을 지닌 vitamin I의 투여는 스트레스로 인한 생체내 산화적 손상을 억제할 수 있을 것으로 생각된다. 이런 효능을 확인하기 위하여 실험용 흰 쥐에게 4주간의 noise 및 고정화 스트레스를 가한 결과, 스트레스를 가함으로서 체중증가량을 감소시켰으며, 스트레스 지표 물질인 5-HIAA와 혈청내 유리 지방산의 증가 및 뇌조직의 산화적 손상이 증가되어 정상적으로 스트레스가 가해졌음을 확인할 수 있었다. 또한, vitamin E 투여군의 경우 혈청내에서의 vitamin E 농도가 유의적으로 증가하여 정상적인 vitamin E의 투여도 이루어졌음을 확인하였다. Vitamin E의 투여는 스트레스로 인한 체중 증가량의 감소를 억제하였으며, 또한 뇌조직의 단백질 및 지질의 산화적 손상을 억제하는 효능을 보였으며, SOD의 활성 또한 증가시키는 효능을 나타냈다. 따라서, vitamin E 투여는 스트레스로 인하여 발생하는 뇌조직의 산화적 손상을 억제함으로서 스트레스에 대한 방어 효능이 일부 있는 것으로 생각된다.

• Molecules and Cells
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• 제41권2호
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• pp.127-133
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• 2018

Chromatin remodeling factors are involved in many cellular processes such as transcription, replication, and DNA damage response by regulating chromatin structure. As one of chromatin remodeling factors, remodeling and spacing factor 1 (RSF1) is recruited at double strand break (DSB) sites and regulates ataxia telangiectasia mutated (ATM) -dependent checkpoint pathway upon DNA damage for the efficient repair. RSF1 is overexpressed in a variety of cancers, but regulation of RSF1 levels remains largely unknown. Here, we showed that protein levels of RSF1 chromatin remodeler are temporally upregulated in response to different DNA damage agents without changing the RSF1 mRNA level. In the absence of SNF2h, a binding partner of RSF1, the RSF1 protein level was significantly diminished. Intriguingly, the level of RSF1-3SA mutant lacking ATM-mediated phosphorylation sites significantly increased, and upregulation of RSF1 levels under DNA damage was not observed in cells overexpressing ATM kinase. Furthermore, failure in the regulation of RSF1 level caused a significant reduction in DNA repair, whereas reconstitution of RSF1, but not of RSF1-3SA mutants, restored DSB repair. Our findings reveal that temporal regulation of RSF1 levels at its post-translational modification by SNF2h and ATM is essential for efficient DNA repair.

• 한국식품과학회지
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• 제49권6호
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• pp.659-667
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• 2017

본 연구는 in vitro에서 나린진과 나린제닌의 항산화 활성을 평가하고, in vivo에서 BALB/c 마우스에 나린진과 나린제닌을 7일 동안 경구투여 한 후 6Gy의 감마선을 조사시켜 24시간 뒤 감마선 조사로 인한 세포 손상 및 산화적 스트레스에 대한 방사선 예방효과를 검토하였다. 나린진과 나린제닌의 항산화 활성평가에서 나린제닌이 나린진보다 ABTS 제거 활성 및 FRAP을 유의적으로 증가시켜 아글리콘 형태인 나린제닌이 글리코사이드 형태의 나린진보다 항산화 능력이 뛰어난 것을 확인하였다. 감마선 조사 전 나린제닌을 투여 한 군이 감마선 조사군에 비해 비장 지수, 흉선 지수 및 백혈구 수치가 증가하여 조혈 면역계 손상에 대해 보호효과가 있음을 확인하였다. 나린제닌을 투여 후 감마선을 조사한 군의 ALT와 AST가 감마선 조사군에 비해 유의적으로 감소하여 간세포 손상에 대한 예방효과를 확인하였다. 감마선 조사 전에 나린제닌을 투여한 군의 지방질과산화는 감마선 조사군에 비해 유의적으로 낮게 나타남을 보였으며, XO는 감마선 조사군에 비해 유의적으로 감소하여 방사선에 의한 장해를 감소시킨 것으로 판단할 수 있다. 감마선 조사 전 나린제닌을 투여한 군의 GSH와 항산화 효소의 활성은 감마선 조사군에 비해 유의적으로 증가하여 생체 내에 항산화 활성을 회복시켰다. 이 상의 결과를 통해 방사선 조사 전에 나린제닌의 투여는 방사선에 의한 세포 손상과 산화적 스트레스에 대해 보호 효과가 있어 방사선보호제로 유용하게 사용될 수 있다.

• 공업화학
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• 제24권5호
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• pp.483-488
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• 2013

본 연구에서는, 레스베라트롤의 산화적 손상대한 세포 보호 효과와 항산화능을 조사하였다. 레스베라트롤의 Free radical (1,1-diphenyl-2-picrylhydrazyl, DPPH) 소거활성은 ($FSC_{50}$) $103{\mu}M$로 나타났다. 루미놀화학발광법을 이용하여 $Fe^{3+}-EDTA/H_2O_2$계에서 레스베라트롤의 활성산소(Reactive oxygen species, ROS) 소거활성은($OSC_{50}$)을 평가하였다. 레스베라트롤은 $0.042{\mu}M$로 나타나 비교물질로 사용한 L-ascorbic acid ($0.405{\mu}M$)보다 9.6배 우수한 활성산소 소거활성을 보였다. 또한 레스베라트롤은 지용성 항산화제로 알려진 (+)-${\alpha}$-tocopherol보다 우수한 세포보호 활성을 나타내었다. 세포독성 조사에서 레스베라트롤은 $50{\mu}M$에서 세포독성을 나타내지 않았다. HaCaT 세포에 $800mJ/cm^2$의 UVB 또는 $30{\mu}M$의 rose-bengal을 처리하였을 때, 레스베라트롤은 농도의존적으로 세포의 산화적 손상에 대항하여 세포를 보호하였다. 그러나 10 mM의 $H_2O_2$를 처리한 경우에, 레스베라트롤은 세포보호 효과를 나타내지 않았다. 이들의 결과들은 레스베라트롤이 항산화능 및 세포보호 효과를 통해서 피부 노화를 예방하고 개선하는데 있어 이용 가능함을 시사한다.