• 제목/요약/키워드: Redox factor-1

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Heme oxygenase-1 유도를 통한 화학 암예방 및 세포보호와 그 분자생물학적 기전 (Chemoprevention and Chemoprotection Through Heme Oxygenase-1 Induction and Underlying Molecular Mechanisms)

  • 김은희;김성환;나혜경;서영준
    • 한국환경성돌연변이발암원학회지
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    • 제26권4호
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    • pp.97-112
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    • 2006
  • Heme oxygenase(HO)-1 is an important antioxidant enzyme that plays a pivotal role in cellular adaptation and protection in response to a wide array of noxious stimuli. Thus, HO-1 induction has been associated with prevention or mitigation of pathogenesis of various diseases, including acute inflammation, atherosclerosis, degenerative diseases, and carcinogenesis. Recent progress in our understanding of the function of molecules in the cellular signaling network as key modulators of gene transcription sheds light on the molecular mechanisms underlyuing HO-1 gene expression. A panel of redox-sensitive transcription factors such as activator protein-1, nuclear factor-kB, and nuclear factor E2-related factor-2, and some of the upstream kinases have been identified as prime regulators of HO-1 gene induction. This review summarizes molecular mechanisms underlying HO-1 expression and the significance of targeted induction of HO-1 as a potential chemopreventive or chemoprotective strategy.

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Heme Oxygenase-1 as a Potential Therapeutic Target for Hepatoprotection

  • Farombi, Ebenezer Olatunde;Surh, Young-Joon
    • BMB Reports
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    • 제39권5호
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    • pp.479-491
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    • 2006
  • Heme oxygenase (HO), the rate limiting enzyme in the breakdown of heme into carbon monoxide (CO), iron and bilirubin, has recently received overwhelming research attention. To date three mammalian HO isozymes have been identified, and the only inducible form is HO-1 while HO-2 and HO-3 are constitutively expressed. Advances in unveiling signal transduction network indicate that a battery of redox-sensitive transcription factors, such as activator protein-1 (AP-1), nuclear factor-kappa B (NF-${\kappa}B$) and nuclear factor E2-related factor-2 (Nrf2), and their upstream kinases including mitogen-activated protein kinases play an important regulatory role in HO-1 gene induction. The products of the HO-catalyzed reaction, particularly CO and biliverdin/bilirubin have been shown to exert protective effects in several organs against oxidative and other noxious stimuli. In this context, it is interesting to note that induction of HO-1 expression contributes to protection against liver damage induced by several chemical compounds such as acetaminophen, carbon tetrachloride and heavy metals, suggesting HO-1 induction as an important cellular endeavor for hepatoprotection. The focus of this review is on the significance of targeted induction of HO-1 as a potential therapeutic strategy to protect against chemically-induced liver injury as well as hepatocarcinogenesis.

γ-Al2O3에 담지된 Cu-Mn 산화물 촉매의 활성 및 특성 (Activity and Characteristics of Cu-Mn Oxide Catalysts Supported on γ-Al2O3)

  • 김혜진;최성우;이창섭
    • Korean Chemical Engineering Research
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    • 제44권2호
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    • pp.193-199
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    • 2006
  • ${\gamma}-Al_2O_3$에 담지한 Cu-Mn 산화물 촉매에서 톨루엔 완전산화 반응을 $160{\sim}280^{\circ}C$의 온도 범위에서 고정층 반응기로 조사하였다. BET, SEM, TPR, TPO, XPS 및 XRD를 이용하여 촉매 특성분석을 하였다. 톨루엔의 완전산화 반응은 $280^{\circ}C$ 이하에서 이루어졌으며, 적절한 Cu-Mn 담지량은 15.0 wt%Cu-10.0 wt%Mn인 것으로 나타났다. TPR/TPO 및 XPS 분석 결과, 15 Cu-10 Mn 촉매의 산화환원 봉우리가 낮은 온도로 이동하였으며 결합에너지가 높은 값으로 이동하였다. XRD 결과, 고분산된 Mn 산화물과 CuO 보다 $Cu_{1.5}Mn_{1.5}O_4$의 촉매활성 인자로서의 역할이 더욱 우수한 것으로 추측되며, 촉매의 활성은 촉매의 산화환원 능력과 촉매의 높은 산화 상태에 기인하는 것으로 사료된다.

Dysregulation of NRF2 in Cancer: from Molecular Mechanisms to Therapeutic Opportunities

  • Jung, Byung-Jin;Yoo, Hwan-Sic;Shin, Sooyoung;Park, Young-Joon;Jeon, Sang-Min
    • Biomolecules & Therapeutics
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    • 제26권1호
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    • pp.57-68
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    • 2018
  • Nuclear factor E2-related factor 2 (NRF2) plays an important role in redox metabolism and antioxidant defense. Under normal conditions, NRF2 proteins are maintained at very low levels because of their ubiquitination and proteasomal degradation via binding to the kelch-like ECH associated protein 1 (KEAP1)-E3 ubiquitin ligase complex. However, oxidative and/or electrophilic stresses disrupt the KEAP1-NRF2 interaction, which leads to the accumulation and transactivation of NRF2. During recent decades, a growing body of evidence suggests that NRF2 is frequently activated in many types of cancer by multiple mechanisms, including the genetic mutations in the KEAP1-NRF2 pathway. This suggested that NRF2 inhibition is a promising strategy for cancer therapy. Recently, several NRF2 inhibitors have been reported with anti-tumor efficacy. Here, we review the mechanisms whereby NRF2 is dysregulated in cancer and its contribution to the tumor development and radiochemoresistance. In addition, among the NRF2 inhibitors reported so far, we summarize and discuss repurposed NRF2 inhibitors with their potential mechanisms and provide new insights to develop selective NRF2 inhibitors.

Oxidative Stress, Chromatin Remodeling and Gene Transcription in Inflammation and Chronic Lung Diseases

  • Rahman, Irfan
    • BMB Reports
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    • 제36권1호
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    • pp.95-109
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    • 2003
  • Inflammatory lung diseases are characterized by chronic inflammation and oxidant/antioxidant imbalance. The sources of the increased oxidative stress in patients with chronic inflammatory lung diseases such as asthma and chronic obstructive pulmonary disease (COPD) derive from the increased burden of inhaled oxidants, and from the increased amounts of reactive oxygen species (ROS) generated by several inflammatory, immune and various structural cells of the airways. Increased levels of ROS produced in the airways is reflected by increased markers of oxidative stress in the airspaces, sputum, breath, lungs and blood in patients with lung diseases. ROS, either directly or via the formation of lipid peroxidation products such as 4-hydroxy-2-nonenal may play a role in enhancing the inflammation through the activation of stress kinases (JNK, MAPK, p38) and redox sensitive transcription factors such as NF-${\kappa}B$ and AP-1. Recent evidences have indicated that oxidative stress and pro-inflammatory mediators can alter nuclear histone acetylation/deacetylation allowing access for transcription factor DNA binding leading to enhanced pro-inflammatory gene expression in various lung cells. Understanding of the mechanisms of redox signaling, NF-${\kappa}B$/AP-1 regulation, the balance between histone acetylation and deacetylation and the release and expression of pro- and anti-inflammatory mediators may lead to the development of novel therapies based on the pharmacological manipulation of antioxidants in lung inflammation and injury. Antioxidants that have effective wide spectrum activity and good bioavailability, thiols or molecules which have dual antioxidant and anti-inflammatory activity, may be potential therapeutic agents which not only protect against the direct injurious effects of oxidants, but may fundamentally alter the underlying inflammatory processes which play an important role in the pathogenesis of chronic inflammatory lung diseases.

산화환원에 따른 hHSF1의 DNA binding domain의 역할 (The Role of DNA Binding Domain in hHSF1 through Redox State)

  • 김솔;황윤정;김희은;여명;김안드레;문지영;강호성;박장수
    • 생명과학회지
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    • 제16권6호
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    • pp.1052-1059
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    • 2006
  • 다양한 종류의 박테리아에서부터 사람의 세포에 이르기까지 환경적인 스트레스나 병에 의한 스트레스 혹은 스트레스가 없는 상황에서도 열충격반응(heat shock response) 유도되어진다. 열충격반응에 노출된 세포에서는 모든 단백질의 발현이 정지되는 반면, 열충격단백질(heat shock proteins: HSPs)은 발현되어 스트레스로부터 세포를 보호한다. HSF1(heat shock factor 1)이라는 HSPs 유도단백질은 열충격반응시 단량체형태에서 삼중체의 형태로 구조변화를 일으켜 heat shock element(HSE)라고 불리우는 HSP gene의 발현 promoter에 특이적으로 결합하게 되어 HSPs를 발현시킨다. Human HSF1(hHSF1)은 다섯 개의 시스테인 잔기를 가지고 있는데 이 시스테인의 thiol(-SH)기는 강한 친전자성을 띔으로 급격히 산화되거나 질산화된다. 이러한 고찰은 시스테인 잔기가 산화 환원 의존적인 황산기/이황화결합 전환을 통해 구조적인 변화를 가져온다는 사실을 의미하고 있다. 따라서 본 연구에서는 여러 가지 산화환원제를 이용하여 HSF1에 존재하는 다섯 개의 시스테인 잔기의 역할과 삼량체 형성에 관여하는 잔기에 대하여 알아보고자 하였다. 또한 이황화결합을 통한 삼량체형성의 구조적변화의 관점에서 HSF1의 구조 변화와 DNA 결합력과의 상관관계에 관하여도 알아보고자 하였다. 본 연구결과로 HSF1의 DNA binding domain은 삼량체를 형성하는 구조적인 변화를 통해서 DNA에 대한 결합력이 증가되는 것을 알 수 있었는데 이것은 삼량체가 됨으로서 HSF1의 내부에 위치해 있던 DNA binding domain이 외부로 노출 되어져 DNA에 쉽게 결합할 수 있게 된다는 사실을 시사한다.

TATA-Binding Protein-Related Factor 2 Is Localized in the Cytoplasm of Mammalian Cells and Much of It Migrates to the Nucleus in Response to Genotoxic Agents

  • Park, Kyoung-ae;Tanaka, Yuji;Suenaga, Yusuke;Tamura, Taka-aki
    • Molecules and Cells
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    • 제22권2호
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    • pp.203-209
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    • 2006
  • TBP (TATA-binding protein)-related factor 2 (TRF2) regulates transcription during a nuber of cellular processes. We previously demonstrated that it is localized in the cytoplasm and is translocated to the nucleus by DNA-damaging agents. However, the cytoplasmic localization of TRF2 is controversial. In this study, we reconfirmed its cytoplasmic localization in various ways and examined its nuclear migration. Stresses such as heat shock, redox agents, heavy metals, and osmotic shock did not affect localization whereas genotoxins such as methyl methanesulfonate (MMS), cisplatin, etoposide, and hydroxyurea caused it to migrate to the nucleus. Adriamycin, mitomycin C and ${\gamma}$-rays had no obvious effect. We determined optimal conditions for the nuclear migration. The proportions of cells with nuclei enriched for TRF2 were 25-60% and 5-10% for stressed cells and control cells, respectively. Nuclear translocation was observed after 1 h, 4 h and 12 h for cisplatin, etoposide and MMS and hydroxyurea, respectively. The association of TRF2 with the chromatin and promoter region of the proliferating cell nuclear antigen (PCNA) gene, a putative target of TRF2, was increased by MMS treatment. Thus TRF2 may be involved in genotoxin-induced transcriptional regulation.

Methods to Improve Light Harvesting Efficiency in Dye-Sensitized Solar Cells

  • Park, Nam-Gyu
    • Journal of Electrochemical Science and Technology
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    • 제1권2호
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    • pp.69-74
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    • 2010
  • Methodologies to improve photovoltaic performance of dye-sensitized solar cell (DSSC) are reviewed. DSSC is usually composed of a dye-adsorbed $TiO_2$ photoanode, a tri-iodide/iodide redox electrolyte and a Pt counter electrode. Among the photovoltaic parameters of short-circuit photocurrent density, open-circuit voltage and fill factor, short-circuit photocurrent density is the collective measure of light harvesting, charge separation and charge collection efficiencies. Internal quantum efficiency is known to reach almost 100%, which indicates that charge separation occurs without loss by recombination. Thus, light harvesting efficiency plays an important role in improvement of photocurrent. In this paper, technologies to improve light harvesting efficiency, including surface area improvement by nano-dispersion, size-dependent light scattering efficiency, bi-functional nano material, panchromatic absorption by selective positioning of three different dyes and transparent conductive oxide (TCO)-less DSSC, are introduced.

Longevity Genes: Insights from Calorie Restriction and Genetic Longevity Models

  • Shimokawa, Isao;Chiba, Takuya;Yamaza, Haruyoshi;Komatsu, Toshimitsu
    • Molecules and Cells
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    • 제26권5호
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    • pp.427-435
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    • 2008
  • In this review, we discuss the genes and the related signal pathways that regulate aging and longevity by reviewing recent findings of genetic longevity models in rodents in reference to findings with lower organisms. We also paid special attention to the genes and signals mediating the effects of calorie restriction (CR), a powerful intervention that slows the aging process and extends the lifespan in a range of organisms. An evolutionary view emphasizes the roles of nutrient-sensing and neuroendocrine adaptation to food shortage as the mechanisms underlying the effects of CR. Genetic and non-genetic interventions without CR suggest a role for single or combined hormonal signals that partly mediate the effect of CR. Longevity genes fall into two categories, genes relevant to nutrient-sensing systems and those associated with mitochondrial function or redox regulation. In mammals, disrupted or reduced growth hormone (GH)-insulin-like growth factor (IGF)-1 signaling robustly favors longevity. CR also suppresses the GH-IGF-1 axis, indicating the importance of this signal pathway. Surprisingly, there are very few longevity models to evaluate the enhanced anti-oxidative mechanism, while there is substantial evidence supporting the oxidative stress and damage theory of aging. Either increased or reduced mitochondrial function may extend the lifespan. The role of redox regulation and mitochondrial function in CR remains to be elucidated.

Evaluation of Methane Emissions with Water Regime before the Cultivation Period in Paddy Fields

  • Park, Jun-Hong;Park, Sang-Jo;Kim, Jong-Su;Seo, Dong-Hwan;Park, So-Deuk;Kim, Jin-Ho
    • 한국토양비료학회지
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    • 제48권4호
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    • pp.271-277
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    • 2015
  • Anaerobic decomposition of organic material in flooded rice fields produces methane, which escapes to the atmosphere primarily by transport through the rice plants. The annual amount of $CH_4$ emitted from a given area of rice is a function of the number and duration of crops grown, water regimes before and during cultivation period, and organic and inorganic soil amendments. Soil type, temperature, and rice cultivar also affect $CH_4$ emissions. The field experiment was conducted for three years to develop methane emission factor for water regime before the cultivation period from the rice fields. It was treated with three different water regimes prior to rice cultivation, namely: non-flooded pre-season < 180 days, non-flooded pre-season > 180 days, flooded per-season in which the minimum flooding interval is set to 30 days. Methane emission increased with days after transplanting and soil redox potential (Eh) decreased rapidly after flooding during the rice cultivation. The average methane emission fluxes were $5.47kg\;CH_4\;ha^{-1}day^{-1}$in flooded pre-season > 30 days, 5.04 in non-flooded pre-season < 180 days and 4.62 in non-flooded pre-season > 180. Methane emission flux was highly correlated with soil temperature and soil Eh. Rice yields showed no difference among treatments with water regime before the cultivation period.