• Title/Summary/Keyword: Thiol redox

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Survival of APC-mutant colorectal cancer cells requires interaction between tankyrase and a thiol peroxidase, peroxiredoxin II

  • Kang, Dong Hoon;Lee, Joanna H.S.;Kang, Sang Won
    • BMB Reports
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    • v.50 no.8
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    • pp.391-392
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    • 2017
  • Overexpression of mammalian 2-Cys peroxiredoxin (Prx) enzymes is observed in most cancer tissues. Nevertheless, their specific roles in colorectal cancer (CRC) progression has yet to be fully elucidated. Here, a novel molecular mechanism by which PrxII/Tankyrase (TNKS) interaction mediates survival of adenomatous polyposis coli (APC)-mutant CRC cells was explored. In mice with an inactivating APC mutation, a model of spontaneous intestinal tumorigenesis, deletion of PrxII reduced intestinal adenomatous polyposis and thereby increased survival. In APC-mutant human CRC cells, PrxII depletion hindered PARP-dependent Axin1 degradation through TNKS inactivation. $H_2O_2-sensitive$ Cys residues in the zinc-binding domain of TNKS1 was found to be crucial for PARsylation activity. Mechanistically, direct binding of PrxII to ARC4/5 domains of TNKS conferred vital redox protection against oxidative inactivation. As a proof-of-concept experiment, a chemical compound targeting PrxII inhibited the growth of tumors xenografted with APC-mutation-positive CRC cells. Collectively, the results provide evidence revealing a novel redox mechanism for regulating TNKS activity such that physical interaction between PrxII and TNKS promoted survival of APC-mutant colorectal cancer cells by PrxII-dependent antioxidant shielding.

Regulation of Apoptosis by Nitrosative Stress

  • Kim, Ki-Mo;Kim, Peter K.M.;Kwon, Young-Guen;Bai, Se-Kyung;Nam, Woo-Dong;Kim, Young-Myeong
    • BMB Reports
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    • v.35 no.1
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    • pp.127-133
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    • 2002
  • Nitrosative stress can prevent or induce apoptosis. It occurs via S-nitrosylation by the interaction of nitric oxide (NO) with the biological thiols of proteins. Cellular redox potential and non-heme iron content determine S-nitrosylation. Apoptotic cell death is inhibited by S-nitrosylation of the redox-sensitive thiol in the catalytic site of caspase family proteases, which play an essential role in the apoptotic signal cascade. Nitrosative stress can also promote apoptosis by the activation of mitochondrial apoptotic pathways, such as the release of cytochrome c, an apoptosis-inducing factor, and endonuclease G from mitochondria, as well as the suppression of NF-${\kappa}B$ activity. In this article we reviewed the mechanisms whereby S-nitrosylation and nitrosative stress regulate the apoptotic signal cascade.

Determining the Self-Assembly and Redox Process of a Viologen Monolayer by Electrochemical Quartz Crystal Microbalance (수정진동자를 이용한 Viologen 단분자막의 자기조립화와 산화,환원 반응 측정)

  • Ock, J.Y.;Song, S.H.;Shin, H.K.;Chang, J.S.;Chang, S.M.;Kwon, Y.S.
    • Proceedings of the Korean Institute of Electrical and Electronic Material Engineers Conference
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    • 2003.05c
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    • pp.23-27
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    • 2003
  • Molecular self-assembled of surfactant viologen are of recent interest because they can from functional electrodes as well as micellar assemblies, which can be profitably utilized for display devices, photoelectrochemical studies and electrocatalysis as electron acceptor or electron mediator. Fromherz et al studied the self-assembly of thiol and disulfide derivatives of viologens bearing long n-alkyl chains on Au electrode surface. The electrochemical behavior of self-assembled viologen monolayer has been investigated with QCM, which has been known as nano-gram order mass detector. The self-assembly process of viologen was monitored using resonant frequency$({\Delta}F)$ and resonant resistance(R). The redox process of viologen was observed with resonant frequency $({\Delta}F)$.

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Optical and Electrochemical Property of Self-Assembled Monolayers Containing Viologen Derivative by EQCM Study (EQCM법을 이용한 자기조립된 Viologen 유도체의 광학적 특성 및 전기화학적 특성 연구)

  • Lee, Dong-Yun;Park, Sang-Hyun;Park, Jae-Chul;Kwon, Young-Soo
    • Proceedings of the KIEE Conference
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    • 2006.07c
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    • pp.1305-1306
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    • 2006
  • A monolayer assembly of anthracene-viologen linked thiol ($AMVC_{8}SH$) was fabricated on a gold electrode by self-assembly method. Structural property of the self-assembled monolayers (SAMs) was carried out by optical and electrochemical method. Firstly, we investigated PL spectrum and UV/visible absorption for the optical properties in solution state. Secondly, we determined the characteristics of charge transfer in different electrolyte solutions by electrochemical quartz crystal microbalance (EQCM). From the data, the PL spectrum and UV/visible absorption were observed and the well-defined shape peaks were nearly equal charges during redox reactions and existed to an excellent linear relationship between the scan rates and existed to currents. The mass change was determined during redox reaction. The mass change behavior of SAMs was not only governed by the mobility of the ion in the viologen but the valence of the ion in the electrolyte solution.

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Role of Protein Disulfide Isomerase in Molecular Fate of Thyroglobulin and its Regulation by Endogenous Oxidants and Reductants

  • Liu, Xi-Wen;Sok, Dai-Eun
    • Archives of Pharmacal Research
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    • v.25 no.4
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    • pp.485-492
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    • 2002
  • The molecular fate of thyroglobulin (Tg) is controlled by oligomerization, a means of storing Tg at high concentrations, and deoligomerization. The oligomerization of bovine Tg are intermolecular reactions that occur through oxidative processes, such as disulfide and dityrosine formation, as well as isopeptide formation; disulfide formation is primarily responsible for Tg oligomerization. Here, the protein disulfide isomerase (PDI) and/or peroxidase-induced oligomerization of unfolded thyroglobulins, which were prepared by treating bovine Tg with heat, urea or thiol/urea, was investigated using SDS-PAGE analyses. In addition, the enzymatic oligomerization was compared with non-enzymatic oligomerization. The thermally-induced oilgomerization of Tg, dependent on glutathione redox state, was affected by the ionic strength or the presence of a surfactant. Meanwhile, PDI-catalyzed oligomerization, time and pH-dependent, was the most remarkable with unfolded/reduced Tg, which was prepared from a treatment with urea/DTT, while the thermally-unfolded Tg was less sensitive. Similarly, the oligomerization of unfolded/reduced Tg was also mediated by peroxidase. However, PDI showed no remarkable effect on the peroxidase-mediated oligomerization of either the unfolded or unfolded/reduced Tg. Additionally, the reductive deoligomerization of oligomeric Tg was exerted by PDI in an excessively reducing state. Based on these results, it is proposed that PDI catalyzes the oligomerization of Tg through the disulfide linkage and its deoligomerization in the molecular fate, and this process may require a specific molecular form of Tg, optimally unfolded/reduced, in a proper redox state.

Electrochemical Properties of Viologen Self-Assembly Monolayer Using QCM (수정진동자를 이용한 Viologen Self-Assembly 단분자막의 전기화학적 특성)

  • 옥진영;신훈규;박재철;장정수;권영수
    • Journal of the Korean Institute of Electrical and Electronic Material Engineers
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    • v.16 no.6
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    • pp.496-500
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    • 2003
  • Molecular self-assembled of surfactant viologen are of recent interest because they can from functional electrodes as well as micellar assemblies, which can be profitably utilized for display devices, photoelectrochemical studies and electrocatalysis as electron acceptor or electron mediator. Fromherz et al studied the self-assembly of thiol and disulfide derivatives of viologens bearing long n-alkyl chains on Au electrode surface[1]. The electrochemical behavior of self-assembled viologen monolayer has been investigated with QCM, which has been known as nano-gram order mass detector. The self-assembly process of viologen was monitored using resonant frequency(ΔF) and resonant resistance(R). The redox process of viologen was observed with resonant frequency(ΔF).

Development of New DNA Chip and Genome Detection Using an Indicator-free Target DNA (비수식화 DNA를 이용한 유전자 검출 및 새로운 DNA칩의 개발)

  • Park, Yong-Sung;Park, Dae-Hee;Kwon, Young-Soo;Tomoji Kawai
    • The Transactions of the Korean Institute of Electrical Engineers C
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    • v.52 no.8
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    • pp.365-370
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    • 2003
  • This research aims to develop an indicator-free DNA chip using micro-fabrication technology. At first, we fabricated a DNA microarray by lithography technology. Several probe DNAs consisting of thiol group at their 5-end were immobilized on the gold electrodes. Then indicator-free target DNA was hybridized by an electrical force and measured electrochemically in potassium ferricyanide solution. Redox peak of cyclic-voltammogram showed a difference between target DNA and mismatched DNA in an anodic peak current. Therefore, it is able to detect various genes electrochemically after immobilization of various probe DNAs and hybridization of indicator-free DNA on the electrodes simultaneously It suggested that this DNA chip could recognize the sequence specific genes.

Development of Next Generation Biochip Using Indicator-free DNA (비수식화 DNA를 이용한 차세대형 바이오칩의 개발)

  • Choi, Yong-Sung;Moon, Jong-Dae;Lee, Kyung-Sup
    • Proceedings of the Korean Institute of Electrical and Electronic Material Engineers Conference
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    • 2006.05a
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    • pp.71-73
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    • 2006
  • This research aims to develop a multiple channel electrochemical DNA chip using micro- fabrication technology. At first, we fabricated a high integrated type DNA chip array by lithography technology. Several probe DNAs consisting of thiol group at their 5-end were immobilized on the gold electrodes. Then target DNAs were hybridized by an electrical force. Redox peak of cyclic-voltammogram showed a difference between target DNA and mismatched DNA in the anodic peak current. Therefore. it is able to detect a various genes electrochemically after immobilization of a various probe DNA and hybridization of label-free DNA on the electrodes simultaneously. It suggested that this DNA chip could recognize the sequence specific genes.

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Development of New Biochip and Genome Detection Using an Non-labeling Target DNA (차세대형 바이오칩의 개발 및 비수식화 표적 DNA를 이용한 유전자 검출)

  • Choi, Yong-Sung;Park, Dae-Hee;Kwon, Young-Soo;Kawai, Tomoji
    • Proceedings of the KIEE Conference
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    • 2002.11a
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    • pp.51-53
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    • 2002
  • This research aims to develop a multiple channel electrochemical DNA chip using micro-fabrication technology. At first, we fabricated a high integrated type DNA chip array by lithography technology. Several probe DNAs consisting of thiol group at their 5-end were immobilized on the sold electrodes. Then target DNAs were hybridized by an electrical force. Redox peak of cyclic-voltammogram showed a difference between target DNA and mismatched DNA in the anodic peak current. Therefore, it is able to detect a various genes electrochemically after immobilization of a various probe DNA and hybridization of label-free DNA on the electrodes simultaneously. It suggested that this DNA chip could recognize the sequence specific genes.

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Overview on Peroxiredoxin

  • Rhee, Sue Goo
    • Molecules and Cells
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    • v.39 no.1
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    • pp.1-5
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    • 2016
  • Peroxiredoxins (Prxs) are a very large and highly conserved family of peroxidases that reduce peroxides, with a conserved cysteine residue, designated the "peroxidatic" Cys ($C_P$) serving as the site of oxidation by peroxides (Hall et al., 2011; Rhee et al., 2012). Peroxides oxidize the $C_P$-SH to cysteine sulfenic acid ($C_P$-SOH), which then reacts with another cysteine residue, named the "resolving" Cys ($C_R$) to form a disulfide that is subsequently reduced by an appropriate electron donor to complete a catalytic cycle. This overview summarizes the status of studies on Prxs and relates the following 10 minireviews.