• 제목/요약/키워드: potential-induced degradation

검색결과 216건 처리시간 0.022초

독활 에탄올 추출물의 대장암 세포에서 Cyclin D1 단백질 분해 유도를 통한 세포 생육 억제활성 (Anti-proliferative Activity of Ethanol Extracts of Root of Aralia cordata var. continentalis through Proteasomal Degradation of Cyclin D1 in Human Colorectal Cancer Cells)

  • 박수빈;박광훈;송훈민;박지혜;신명수;손호준;엄유리;정진부
    • 한국약용작물학회지
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    • 제25권5호
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    • pp.328-334
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    • 2017
  • Background: In this study, we evaluated the anti-cancer activity and potential molecular mechanism of 70% ethanol extracts of the root of Aralia cordata var. continentalis (Kitagawa) Y. C. Chu (RAc-E70) against human colorectal cancer cells. Methods and Results: RAc-E70 suppressed the proliferation of the human colorectal cancer cell lines, HCT116 and SW480. Although RAc-E70 reduction cyclin D1 expression at the protein and mRNA levels, RAc-E70-induced reduction in cyclin D1 protein level occurred more dramatically than that of cyclin D1 mRNA. The RAc-E70-induced downregulation of cyclin D1 expression was attenuated in the presence of MG132. Additionally, RAc-E70 reduced HA-cyclin D1 levels in HCT116 cells transfected with HA-tagged wild type-cyclin D1 expression vector. RAc-E70-mediated cyclin D1 degradation was blocked in the presence of LiCl, a $GSK3{\beta}$ inhibitorbut, but not PD98059, an ERK1/2 inhibitor and SB203580, a p38 inhibitor. Furthermore, RAc-E70 phosphorylated cyclin D1 at threonine-286 (T286), and LiCl-induced $GSK3{\beta}$ inhibition reduced the RAc-E70-mediated phosphorylation of cyclin D1 at T286. Conclusions: Our results suggested that RAc-E70 may downregulate cyclin D1 expression as a potential anti-cancer target through $GSK3{\beta}$-dependent cyclin D1 degradation. Based on these findings, RAc-E70 maybe a potential candidate for the development of chemopreventive or therapeutic agents for human colorectal cancer.

교류전류를 이용한 새로운 비파괴탐상법의 개발;표면결함과 이면결함의 평가 및 실기 부재의 결함 검출 (Development of the Advanced NDI Technique Using an Alternating Current : the Evaluation of surface crack and blind surface crack and the detection of defects in a field component)

  • 김훈;임재규
    • Journal of Welding and Joining
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    • 제13권2호
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    • pp.42-52
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    • 1995
  • In the evaluation of aging degradation on the structural materials based on the fracture mechanics, the detection and size prediction of defect are very important. Aiming at nondestructive detection and size prediction ol defect with high accuracy and resolution, therefore, an lnduced Current Focusing Potential Drop(ICFPD) technique has been developed. The principle of this technique is to induce a focusing current at an exploratory region by an induction wire flowing an alternating current(AC) that is a constant ampere and frequency. Defects are assessed with the potential drops that are measured the induced current on the surface of metallic material by the potential pick-up pins. In this study, the lCFPD technique was applied for evaluating the location and size of the surface crack and blind crack made in plate specimens, and also for detecting the defects existing in valve, a field component, that were developed by SCC etc. during the service. The results of this present study show that surface crack and blind crack are able to defect with potential drop. these cracks are distinguished with the distribution of potential drop, and the crack depths can be estimated with each normalized potential drop that are parameters estimating the depth of each type crack. In the field component, the defects estimated by experiment result correspond with those in the cutting face of the measuring point within a higher sensitivity.

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Protective effects against alcoholic liver damage: potential of herbal juice (HJ), blend of Zingiber officinale Roscoe and Pueraria lobata Ohwi extracts

  • 정영윤;최유연;양웅모;안광석
    • 대한융합한의학회지
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    • 제5권1호
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    • pp.45-54
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    • 2023
  • Objectives : Alcohol-induced liver disease advances as to reactive oxygen species (ROS) and cellular lipid peroxidation increase. We examined the hepatoprotective effects of Zingiber officinale Roscoe rhizome extract (ZR), Pueraria lobata Ohwi flower extracts (PF), and a newly developed herbal juice (HJ), which was a combination of ZR and PF extracts, against ethanol-induced hepatotoxicity. Methods: The study utilized the human hepatoma cell line HepG2 cells to validate the hepatoprotective effect of HJ (50~200 ㎍/mL) against ethanol (EtOH, 700 mM)-induced liver damage. Results: HJ effectively reduced the protein expression of sterol regulatory element-binding transcription factor 1, adiponectin, and AMP-activated protein kinase in EtOH-induced HepG2 cells. The levels of ROS, total cholesterol, and triglycerides, which are the result of various synthesis and lipogenesis processes induced by EtOH in the liver, were reduced by HJ. Furthermore, the activities of alcohol dehydrogenase and aldehyde dehydrogenase, enzymes linked to alcohol degradation, were more effectively downregulated by HJ treatment compared to treatment with ZR and PF alone, all without causing cytotoxic effects. Conclusions: HJ protects the liver by inhibiting EtOH-induced lipogenesis, lowering ROS generation, and improving alcohol degradation, which is more effective than ZR and PF alone. Further, in vivo experiments can offer additional evidence regarding the effectiveness, safety, and underlying mechanism of action of HJ.

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Bortezomib Is Toxic but Induces Neurogenesis and Inhibits TUBB3 Degradation in Rat Neural Stem Cells

  • Seung Yeon Sohn;Thin Thin San;Junhyung Kim;Hyun-Jung Kim
    • Biomolecules & Therapeutics
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    • 제32권1호
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    • pp.65-76
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    • 2024
  • Bortezomib (BTZ) is a proteasome inhibitor used to treat multiple myeloma (MM). However, the induction of peripheral neuropathy is one of the major concerns in using BTZ to treat MM. In the current study, we have explored the effects of BTZ (0.01-5 nM) on rat neural stem cells (NSCs). BTZ (5 nM) induced cell death; however, the percentage of neurons was increased in the presence of mitogens. BTZ reduced the B-cell lymphoma 2 (Bcl-2)/Bcl-2 associated X protein ratio in proliferating NSCs and differentiated cells. Inhibition of βIII-tubulin (TUBB3) degradation was observed, but not inhibition of glial fibrillary acidic protein degradation, and a potential PEST sequence was solely found in TUBB3. In the presence of growth factors, BTZ increased cAMP response element-binding protein (CREB) phosphorylation, brain-derived neurotrophic factor (Bdnf) transcription, BDNF expression, and Tubb3 transcription in NSCs. However, in the neuroblastoma cell line, SH-SY5Y, BTZ (1-20 nM) only increased cell death without increasing CREB phosphorylation, Bdnf transcription, or TUBB3 induction. These results suggest that although BTZ induces cell death, it activates neurogenic signals and induces neurogenesis in NSCs.

진균독소 Gliotoxin-유도성 산화적 손상에 의한 Apoptosis (Gliotoxin-Induced Oxidative Stress Mediates the Apoptotic Death in Human Leukemic HL-60 cells)

  • 장해란;김영희;김남송;원진숙;조정환;윤재도;임창인;김호찬;최익준
    • Toxicological Research
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    • 제18권3호
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    • pp.275-283
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    • 2002
  • Fungal metabolite, gliotoxin is an epipolythiodioxopiperazin (ETP) class and has various roles including immunomodulatory and apoptotic effects. This study was designed to evaluate the mechanism by which gliotoxin exerts the apoptosis on human promyelocytic leukemic HL-60 cells. Herein, we demonstrated that the gliotoxin decreased the cell viability in a time-dependent manner Gliotoxin-induced cell death was confirmed us apoptosis characterized by chromatin condensation and ladder-pattern fragmentation of genomic DNA. Gliotoxin increased the catalytic activities of caspase-3 and caspase-9. Activation of caspase-3 was further confirmed by degradation of procaspase-3 and poly(ADP-ribose) polymerase (PARP) by gliotoxin in HL-60 cells. Furthermore, gliotoxin induced the changes of mitochondrial transmembrane potential (MTP). Antioxidants, including GSH and NAC, markedly inhibited apoptosis with conistent suppression of enzymatic activity of caspase-3, caspase-9, and MTP loss in gliotoxin-treated cells. Taken together, we suggest that gliotoxin function as an oxidant and ploys proapoptotic roles in HL-60 cells via activation of intrinsic caspase cascades as well as mitochondrial dysfunction.

Transient Receptor Potential Cation Channel V1 (TRPV1) Is Degraded by Starvation- and Glucocorticoid-Mediated Autophagy

  • Ahn, Seyoung;Park, Jungyun;An, Inkyung;Jung, Sung Jun;Hwang, Jungwook
    • Molecules and Cells
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    • 제37권3호
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    • pp.257-263
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    • 2014
  • A mammalian cell renovates itself by autophagy, a process through which cellular components are recycled to produce energy and maintain homeostasis. Recently, the abundance of gap junction proteins was shown to be regulated by autophagy during starvation conditions, suggesting that transmembrane proteins are also regulated by autophagy. Transient receptor potential vanilloid type 1 (TRPV1), an ion channel localized to the plasma membrane and endoplasmic reticulum (ER), is a sensory transducer that is activated by a wide variety of exogenous and endogenous physical and chemical stimuli. Intriguingly, the abundance of cellular TRPV1 can change dynamically under pathological conditions. However, the mechanisms by which the protein levels of TRPV1 are regulated have not yet been explored. Therefore, we investigated the mechanisms of TRPV1 recycling using HeLa cells constitutively expressing TRPV1. Endogenous TRPV1 was degraded in starvation conditions; this degradation was blocked by chloroquine (CLQ), 3MA, or downregulation of Atg7. Interestingly, a glucocorticoid (cortisol) was capable of inducing autophagy in HeLa cells. Cortisol increased cellular conversion of LC3-I to LC-3II, leading autophagy and resulting in TRPV1 degradation, which was similarly inhibited by treatment with CLQ, 3MA, or downregulation of Atg7. Furthermore, cortisol treatment induced the colocalization of GFP-LC3 with endogenous TRPV1. Cumulatively, these observations provide evidence that degradation of TRPV1 is mediated by autophagy, and that this pathway can be enhanced by cortisol.

Safflower Seed Oil and Its Active Compound Acacetin Inhibit UVB-Induced Skin Photoaging

  • Jeong, Eun Hee;Yang, Hee;Kim, Jong-Eun;Lee, Ki Won
    • Journal of Microbiology and Biotechnology
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    • 제30권10호
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    • pp.1567-1573
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    • 2020
  • Ultraviolet (UV) is one of the major factors harmful to skin health. Irradiation with ultraviolet accelerates the decline of skin function, causing the skin to have deep wrinkles, dryness, decreased procollagen production, and degradation of collagen. Novel materials are needed to prevent the aging of the skin by blocking the effects of UV. Safflower seed oil (Charthamus tinctorius L., SSO) contains significantly high levels of unsaturated fatty acids and phytochemicals. SSO has been traditionally used in China, Japan, and Korea to improve skin and hair. Our objective in this study was to determine the effect of SSO and its active compound acacetin on UVB-induced skin photoaging in HaCaT cells and human dermal fibroblasts (HDF). SSO inhibited UVB-induced matrix metalloproteinase-1 (MMP-1) at both protein and mRNA levels in HaCaT cells and HDF. MMP-1 is known to play important roles in collagen degradation and wrinkle formation. Acacetin, a type of flavonoid, is present in SSO. Similar to SSO, acacetin also inhibited UVB-induced MMP-1 protein and mRNA levels in HaCaT cells and HDF. MMP-1 mRNA is primarily regulated by the mitogen-activated kinase (MAPK) signaling pathway. Acacetin regulated the phosphorylation of JNK1/2 and c-jun, but did not inhibit the phosphorylation of ERK1/2, p38 and AKT. Taken together, these results indicate that SSO and its active compound acacetin can prevent UVB-induced MMP-1 expression, which leads to skin photoaging, and may therefore have therapeutic potential as an anti-wrinkle agent to improve skin health.

Effect of quercetin on the production of nitric oxide in murine macrophages stimulated with lipopolysaccharide from Prevotella intermedia

  • Cho, Yun-Jung;Kim, Sung-Jo
    • Journal of Periodontal and Implant Science
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    • 제43권4호
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    • pp.191-197
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    • 2013
  • Purpose: Nitric oxide (NO) is a short-lived bioactive molecule that is known to play an important role in the pathogenesis of periodontal disease. In the current study, we investigated the effect of the flavonoid quercetin on the production of NO in murine macrophages activated with lipopolysaccharide (LPS) from Prevotella intermedia, a pathogen related to inflammatory periodontal disease, and tried to elucidate the underlying mechanisms of action. Methods: LPS was isolated from P. intermedia ATCC 25611 cells by the standard hot phenol-water method. The concentration of NO in cell culture supernatants was determined by measuring the accumulation of nitrite. Inducible NO synthase (iNOS) and heme oxygenase-1 (HO-1) protein expression, phosphorylation of c-Jun N-terminal kinase (JNK) and p38, inhibitory ${\kappa}B$ $(I{\kappa}B)-{\alpha}$ degradation, and signal transducer and activator of transcription 1 (STAT1) phosphorylation were analyzed via immunoblotting. Results: Quercetin significantly attenuated iNOS-derived NO production in RAW246.7 cells activated by P. intermedia LPS. In addition, quercetin induced HO-1 protein expression in cells activated with P. intermedia LPS. Tin protoporphyrin IX (SnPP), a competitive inhibitor of HO-1, abolished the inhibitory effect of quercetin on LPS-induced NO production. Quercetin did not affect the phosphorylation of JNK and p38 induced by P. intermedia LPS. The degradation of $I{\kappa}B-{\alpha}$ induced by P. intermedia LPS was inhibited when the cells were treated with quercetin. Quercetin also inhibited LPS-induced STAT1 signaling. Conclusions: Quercetin significantly inhibits iNOS-derived NO production in murine macrophages activated by P. intermedia LPS via anti-inflammatory HO-1 induction and inhibition of the nuclear factor-${\kappa}B$ and STAT1 signaling pathways. Our study suggests that quercetin may contribute to the modulation of host-destructive responses mediated by NO and appears to have potential as a novel therapeutic agent for treating inflammatory periodontal disease.

흙의 종류에 따른 강도와 강성저하 특성 (Degradation Characteristics of Strength and Stiffness due to Soils)

  • 송병웅;김홍택;안원일재;촌상철;박인준
    • 한국지반공학회:학술대회논문집
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    • 한국지반공학회 2004년도 춘계학술발표회
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    • pp.253-260
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    • 2004
  • Many scholars and researchers has been studied for many kinds of soil characteristics, but a lot of part are still unsolved. Cyclic load-induced decreasing characteristics of strength and stiffness of soils are also well not known among them. To know that, the characteristics of five kinds of soils; clay, plastic and non-plastic silt, sand, and a weathered soil are compared with dividing two types as plastic or non-plastic soils through direct simple shear(DSS) test. From the results of DSS test, it is known that decreasing characteristics of strength and stiffness are different according to soil types. The strength of plastic and non-plastic soils increases with increment of plasticity index and decrement of volume decrease potential, respectively. And the decreasing stiffness of plastic and non-plastic soils increases with decrement of plasticity index and increment of volume decrease potential, respectively.

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RNA Interference in Infectious Tropical Diseases

  • Kang, Seok-Young;Hong, Young-S.
    • Parasites, Hosts and Diseases
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    • 제46권1호
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    • pp.1-15
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    • 2008
  • Introduction of double-stranded RNA (dsRNA) into some cells or organisms results in degradation of its homologous mRNA, a process called RNA interference (RNAi). The dsRNAs are processed into short interfering RNAs (siRNAs) that subsequently bind to the RNA-induced silencing complex (RISC), causing degradation of target mRNAs. Because of this sequence-specific ability to silence target genes, RNAi has been extensively used to study gene functions and has the potential to control disease pathogens or vectors. With this promise of RNAi to control pathogens and vectors, this paper reviews the current status of RNAi in protozoans, animal parasitic helminths and disease-transmitting vectors, such as insects. Many pathogens and vectors cause severe parasitic diseases in tropical regions and it is difficult to control once the host has been invaded. Intracellularly, RNAi can be highly effective in impeding parasitic development and proliferation within the host. To fully realize its potential as a means to control tropical diseases, appropriate delivery methods for RNAi should be developed, and possible off-target effects should be minimized for specific gene suppression. RNAi can also be utilized to reduce vector competence to interfere with disease transmission, as genes critical for pathogenesis of tropical diseases are knockdowned via RNAi.