• 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.

• Molecules and Cells
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• 제39권1호
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• pp.20-25
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• 2016

Photosynthesis is a highly robust process allowing for rapid adjustment to changing environmental conditions. The efficient acclimation depends on balanced redox metabolism and control of reactive oxygen species release which triggers signaling cascades and potentially detrimental oxidation reactions. Thiol peroxidases of the peroxiredoxin and glutathione peroxidase type, and ascorbate peroxidases are the main peroxide detoxifying enzymes of the chloroplast. They use different electron donors and are linked to distinct redox networks. In addition, the peroxiredoxins serve functions in redox regulation and retrograde signaling. The complexity of plastid peroxidases is discussed in context of suborganellar localization, substrate preference, metabolic coupling, protein abundance, activity regulation, interactions, signaling functions, and the conditional requirement for high antioxidant capacity. Thus the review provides an opinion on the advantage of linking detoxification of peroxides to different enzymatic systems and implementing mechanisms for their inactivation to enforce signal propagation within and from the chloroplast.

• Toxicological Research
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• 제35권4호
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• pp.303-310
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• 2019

We are exposed to numerous xenobiotic electrophiles on a daily basis through the environment, lifestyle, and dietary habits. Although such reactive species have been associated with detrimental effects, recent accumulated evidence indicates that xenobiotic electrophiles appear to act as signaling molecules. In this review, we introduce our findings on 1) activation of various redox signaling pathways involved in cell proliferation, detoxification/excretion of electrophiles, quality control of cellular proteins, and cell survival during exposure to xenobiotic electrophiles at low concentrations through covalent modification of thiol groups in sensor proteins, and 2) negative regulation of reactive sulfur species (RSS) in the modulation of redox signaling and toxicity caused by xenobiotic electrophiles.

• 한국미생물·생명공학회지
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• 제35권1호
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• pp.36-40
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• 2007

Redox signaling은 단백질을 산화환원 시키는 세포의 중요 신호가 전달되어, 그 단백질의 기능이 변화함으로써 세포의 성장 및 사멸을 조절하게 되는 과정이다. 단백질 합성 구성원의 산화, 환원 과정에 의한 단백질 합성 조절을 알아보기 위해 환원제인 DTT 존재 하에 단백질 합성 활성을 관찰한 결과 DTT가 존재하지 않는 것에 비해 단백질합성이 1.4배 정도 증가됨이 관찰되어 redox potential을 보이는 것으로 보아 환원제가 단백질 합성을 좀 더 증진시키는 것으로 사료된다. DTT에 의한 이러한 현상은 산화환원 조절 단백질인 thioredoxin를 첨가한다면 thiol기에 환원력이 전달되어 단백질합성이 더욱 촉진되기 때문에 효모에서 thioredoxin유전자를 cloning하고 이로부터 효모에서 GST-thioredoxin을 분리하였다. DTT 존재 하에 산화환원 조절 단백질인 thioredoxin을 농도별로 첨가하였을 때의 단백질 합성이 어떻게 조절되는지 알아보았다. 반응 액에 DTT를 넣은 것과 넣지 않은 것을 사용하여 thioredoxin을 0ng, 18ng, 90ng, 460ng, 2,300 ng의 농도로 각각 넣어서 반응시켜 보았다. 이렇게 반응시킨 반응물에서 만들어진 단백질 활성을 측정하였는데 thioredoxin의 농도가 높아질수록 그 활성이 높게 나타났으며, thioredoxin을 넣은 것이 넣지 않은 것에 비해 활성이 약 4배 이상 높게 나왔다 이 결과는 산화환원 조절 단백질인 thioredoxin이 환원력을 단백질합성구성원에 효율적으로 전달하는데 관여함을 보여주는 것이며, 산화환원이 단백질 합성 시 중요한 신호전달 과정임을 암시한다.

• Molecules and Cells
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• 제26권4호
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• pp.329-337
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• 2008

Src-family kinases are critically involved in the control of cytoskeleton organization and in the generation of integrin-dependent signaling responses, inducing tyrosine phosphorylation of many signaling and cytoskeletal proteins. Activity of the Src family of tyrosine kinases is tightly controlled by inhibitory phosphorylation of a carboxy-terminal tyrosine residue, inducing an inactive conformation through binding with its SH2 domain. Dephosphorylation of C-ter tyrosine, as well as its deletion of substitution with phenylalanine in oncogenic Src kinases, leads to autophosphorylation at a tyrosine in the activation loop, thereby leading to enhanced Src activity. Beside this phophorylation/dephosphorylation circuitry, cysteine oxidation has been recently reported as a further mechanism of enzyme activation. Mounting evidence describes Src activation via its redox regulation as a key outcome in several circumstances, including growth factor and cytokines signaling, integrin-mediated cell adhesion and motility, membrane receptor cross-talk as well in cell transformation and tumor progression. Among the plethora of data involving Src kinase in physiological and pathophysiological processes, this review will give emphasis to the redox component of the regulation of this master kinase.

• Molecules and Cells
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• 제39권1호
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• pp.65-71
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• 2016

A challenge in the redox field is the elucidation of the molecular mechanisms, by which $H_2O_2$ mediates signal transduction in cells. This is relevant since redox pathways are disturbed in some pathologies. The transcription factor OxyR is the $H_2O_2$ sensor in bacteria, whereas Cys-based peroxidases are involved in the perception of this oxidant in eukaryotic cells. Three possible mechanisms may be involved in $H_2O_2$ signaling that are not mutually exclusive. In the simplest pathway, $H_2O_2$ signals through direct oxidation of the signaling protein, such as a phosphatase or a transcription factor. Although signaling proteins are frequently observed in the oxidized state in biological systems, in most cases their direct oxidation by $H_2O_2$ is too slow ($10^1M^{-1}s^{-1}$ range) to outcompete Cys-based peroxidases and glutathione. In some particular cellular compartments (such as vicinity of NADPH oxidases), it is possible that a signaling protein faces extremely high $H_2O_2$ concentrations, making the direct oxidation feasible. Alternatively, high $H_2O_2$ levels can hyperoxidize peroxiredoxins leading to local building up of $H_2O_2$ that then could oxidize a signaling protein (floodgate hypothesis). In a second model, $H_2O_2$ oxidizes Cys-based peroxidases that then through thiol-disulfide reshuffling would transmit the oxidized equivalents to the signaling protein. The third model of signaling is centered on the reducing substrate of Cys-based peroxidases that in most cases is thioredoxin. Is this model, peroxiredoxins would signal by modulating the thioredoxin redox status. More kinetic data is required to allow the identification of the complex network of thiol switches.

• Molecules and Cells
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• 제28권3호
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• pp.139-148
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• 2009

Cell death has been traditionally classified in apoptosis and necrosis. Apoptosis, known as programmed cell death, is an active form of cell death mechanism that is tightly regulated by multiple cellular signaling pathways and requires ATP for its appropriate process. Apoptotic death plays essential roles for successful development and maintenance of normal cellular homeostasis in mammalian. In contrast to apoptosis, necrosis is classically considered as a passive cell death process that occurs rather by accident in disastrous conditions, is not required for energy and eventually induces inflammation. Regardless of different characteristics between apoptosis and necrosis, it has been well defined that both are responsible for a wide range of human diseases. Glycogen storage disease type I (GSD-I) is a kind of human genetic disorders and is caused by the deficiency of a microsomal protein, glucose-6-phosphatase-${\alpha}$ ($G6Pase-{\alpha}$) or glucose-6-phosphate transporter (G6PT) responsible for glucose homeostasis, leading to GSD-Ia or GSD-Ib, respectively. This review summarizes cell deaths in GSD-I and mostly focuses on current knowledge of the neutrophil apoptosis in GSD-Ib based upon ER stress and redox signaling.

• 한국미생물학회:학술대회논문집
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• 한국미생물학회 2000년도 추계학술발표대회
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• pp.3-5
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• 2000

• 한국광과학회:학술대회논문집
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• 한국광과학회 2005년도 제12회 학술대회 논문초록
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• pp.49-49
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• 2005

• The Korean Journal of Physiology and Pharmacology
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• 제14권3호
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• pp.139-144
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• 2010

In this study, we evaluated the role of apurinic/apyrimidinic endonuclease1/redox factor-1 (Ref-1) on the tumor necrosis factor-$\alpha$ (TNF-$\alpha$) induced cyclooxygenase-2 (COX-2) expression using A549 lung adenocarcinoma cells. TNF-$\alpha$ induced the expression of COX-2 in A549 cells, but did not induce BEAS-2B expression. The expression of COX-2 in A549 cells was TNF-$\alpha$ dose-dependent (5~100 ng/ml). TNF-$\alpha$-stimulated A549 cells evidenced increased Ref-1 expression in a dose-dependent manner. The adenoviral transfection of cells with AdRef-1 inhibited TNF-$\alpha$-induced COX-2 expression relative to that seen in the control cells ($Ad{\beta}gal$). Pretreatment with $10\;{\mu}M$ of SB203580 suppressed TNF-$\alpha$-induced COX-2 expression, thereby suggesting that p38 MAPK might be involved in COX-2 expression in A549 cells. The phosphorylation of p38 MAPK was increased significantly after 5 minutes of treatment with TNF-$\alpha$, reaching a maximum level at 10 min which persisted for up to 60 min. However, p38MAPK phosphorylation was markedly suppressed in the Ref-1-overexpressed A549 cells. Taken together, our results appear to indicate that Ref-1 negatively regulates COX-2 expression in response to cytokine stimulation via the inhibition of p38 MAPK phosphorylation. In the lung cancer cell lines, Ref-1 may be involved as an important negative regulator of inflammatory gene expression.