• 제목/요약/키워드: Cell disruption

검색결과 313건 처리시간 0.02초

다양한 환경변이원의 분자독성학적 메커니즘 연구에 있어서 항종양 인자 p53의 중요성 고찰 (The Overview of the Importances of Tumor Suppressor p53 for Investigating Molecular Toxicological Mechanisms of Various Environmental Mutagens)

  • 정화진;류재천;서영록
    • Environmental Analysis Health and Toxicology
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    • 제19권3호
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    • pp.321-326
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    • 2004
  • The study of p53 tumor suppressor protein is one of most important subjects in an environmental toxicology as well as in cancer biology. Generally, p53 has been known to involve the cell cycle regulation and apoptosis by the activation of its target genes such as p21 and bax in a number of cellular stress responses. In addition, associations of p53 with cellular proteins presumably reflect the involvement of p53 in critical cellular processes such as DNA repair. The complex formation of p53 and exogenous proteins such as viral or cellular proteins has been shown in many cases to play important roles in carcinogenic processes against environmental mutagen. Recently, the disruption of p53 protein by oxidative stress has been also reported to have relevance to carcinogenesis. These findings suggested that the maintaining of stability and functional activity of p53 protein was also important aspect to play as a tumor suppressor protein. Therefore, the detection of functional status of p53 proteins might be an effective biomarker for the cancer and human diseases under the environmental toxicologic carcinogen.

Pre-clinical QT Risk Assessment in Pharmaceutical Companies - Issues of Current QT Risk Assessment -

  • Takasuna, Kiyoshi; Katsuyoshi, Chiba;Manabe, Sunao
    • Biomolecules & Therapeutics
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    • 제17권1호
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    • pp.1-11
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    • 2009
  • Since the Committee for Proprietary Medicinal Products (CPMP) of the European Union issued in 1997 a "points to consider" document for the assessment of the potential for QT interval prolongation by non-cardiovascular agents to predict drug-induced torsades de pointes (TdP), the QT liability has become the critical safety issue in the development of pharmaceuticals. As TdP is usually linked to delayed cardiac repolarization, international guideline (ICH S7B) has advocated the standard repolarization assays such as in vitro IKr (hERG current) and in vivo QT interval, or in vitro APD (as a follow up) as the best biomarkers for predicting the TdP risk. However, the recent increasing evidence suggests that the currently used above biomarkers and/or assays are not fully predictive for TdP, but also does not address potential new druginduced TdP due to the selective disruption of hERG protein trafficking to the cell membrane or VT and/or VF with QT shortening. There is, therefore, an urgent need for other surrogate markers or assays that can predict the proarrhythmic potential of drug candidate. In this review, we provide an ideal pre-clinical strategy to predict the potentials of QT liability and lethal arrhythmia of the drug candidates with recent issues in this field in mind, not at the expense of discarding therapeutically innovative drugs.

전통 약용 식물 권백(Selaginella tamariscina)의 항암효과에 대한 혈액 암세포주 U937의 감수성 및 그 작용기구에 대한 분자생물학적 연구 (Molecular-vased sensitivity of human leukemia cell line U937 to antineoplastic activity in a traditional medicinal plants(Selaginella tamariscina))

  • 이인자;이인선;박성희
    • 한국식품위생안전성학회지
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    • 제11권1호
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    • pp.71-75
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    • 1996
  • In order to study the antitumoral effect of Selaginella tamariscina extracts, the cytotoxicities to human histiocytic leukemia cells (U937) and lymphocyte were measured by MTT method. The water extract of Selaginella tamariscina was partitioned into chloroform (CHCl3), ethylacetate (EtAc), n-butanol (BuOH) and water (H2O), successively. CHCl3, EtAc and BuOH fractions of Selaginella tamariscina showed the cytotoxicity to the U937 cells but they had effect on the cytotoxicity of lymphocyte under the same conditions. The tumor-specific cytotoxicity of Selaginella tamariscina fractions migh have been attributed to their genotoxic effect on actively proliferating cells. The expression of p53 tumor suppressor gene was then evaluated by northern blotting. The increased expression of p53 was induced by Selaginella tamariscina fraction V but no expression of p53 was induced by CHCl3, EtAc, and BuOH fractions of Selaginella tamariscina water extract (fraction V) should be required for the cytotoxcity on U937 and the other fractions of Selaginella tamariscina mediated the U937 disruption.

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NF-kB Activation by Disruption of Microtubule Array during Myogenesis of L6 Cells

  • Sangmyung Rhee;Lee, Kun-Ho;Hyockman Kwon
    • Animal cells and systems
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    • 제1권1호
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    • pp.63-69
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    • 1997
  • We have previously reported that NF-kB is involved in the regulation of nitric oxide synthase gene expression during differentiation of chick embryonic myoblasts. However, how NF-kB is timely activated during myogenesis remains elusive. One of the most prominent events in myogenesis is myoblast membrane fusion, which is accompanied with massive cytoskeletal reorganization. Here we show that the activity of NF-kB markedly increases in L6 rat myogenic cells that have just initiated morphological changes by treating nocodazole, a microtubule-disrupting agent. Furthermore, the induction of NF-kB activation was closely correlated with the myoblast fusion. In addition, a variety of agents that disrupt microtubules stimulated the myoblast fusion as well as the induction of NF-kB activation. In contrast, taxol, a microtubule-stabilizing agent, suppressed the induction of NF-kB activation and inhibited spontaneous differentiation of L6 cells as well. In addition, we found that the NF-KB in the cells consists of p50/p65 heterodimers. These results support the idea that reorganization of microtubule at early stages of differentiation plays a role as a signal for NF-KB activation during myogenesis.

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Lactococcus sp. 1112-1 균주가 생산하는 Bacteriocin의 정제 및 성질 (Purification and Properties of Bacteriocin Produced by Lactococcus sp. 1112-1)

  • 최신양;이상호;유진영;정건섭;구영조;이인선
    • 한국미생물·생명공학회지
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    • 제19권3호
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    • pp.209-214
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    • 1991
  • Lactococcus sp. 1112-1 균주가 생산하는 bacteriocin을 정제하고 특성을 조사하였다. CM-sephadex ion exchange column chromatography, Sephadex G-50 gel filtration, SDS-PAGE를 행함으로서 수율 16.2 정제도 123배의 단일물질을 얻었다. 이 물질은 열에 비교적 안정하여 $60^{\circ}C$에서 60분간 열처리 할 때 38의 잔존활성을 유지하였으며 알카리쪽에서는 비교적 불안정하여 pH 8.0에서 48시간 처리시 77의 활성을 소실하였다. 이 물질은 26개의 아미노산 잔기를 이루고 있었다.

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Effective Thermal Inactivation of the Spores of Bacillus cereus Biofilms Using Microwave

  • Park, Hyong Seok;Yang, Jungwoo;Choi, Hee Jung;Kim, Kyoung Heon
    • Journal of Microbiology and Biotechnology
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    • 제27권7호
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    • pp.1209-1215
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    • 2017
  • Microwave sterilization was performed to inactivate the spores of biofilms of Bacillus cereus involved in foodborne illness. The sterilization conditions, such as the amount of water and the operating temperature and treatment time, were optimized using statistical analysis based on 15 runs of experimental results designed by the Box-Behnken method. Statistical analysis showed that the optimal conditions for the inactivation of B. cereus biofilms were 14 ml of water, $108^{\circ}C$ of temperature, and 15 min of treatment time. Interestingly, response surface plots showed that the amount of water is the most important factor for microwave sterilization under the present conditions. Complete inactivation by microwaves was achieved in 5 min, and the inactivation efficiency by microwave was obviously higher than that by conventional steam autoclave. Finally, confocal laser scanning microscopy images showed that the principal effect of microwave treatment was cell membrane disruption. Thus, this study can contribute to the development of a process to control food-associated pathogens.

Mass Spectrometry-Based Screening Platform Reveals Orco Interactome in Drosophila melanogaster

  • Yu, Kate E.;Kim, Do-Hyoung;Kim, Yong-In;Jones, Walton D.;Lee, J. Eugene
    • Molecules and Cells
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    • 제41권2호
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    • pp.150-159
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    • 2018
  • Animals use their odorant receptors to receive chemical information from the environment. Insect odorant receptors differ from the G protein-coupled odorant receptors in vertebrates and nematodes, and very little is known about their protein-protein interactions. Here, we introduce a mass spectrometric platform designed for the large-scale analysis of insect odorant receptor protein-protein interactions. Using this platform, we obtained the first Orco interactome from Drosophila melanogaster. From a total of 1,186 identified proteins, we narrowed the interaction candidates to 226, of which only two-thirds have been named. These candidates include the known olfactory proteins Or92a and Obp51a. Around 90% of the proteins having published names likely function inside the cell, and nearly half of these intracellular proteins are associated with the endomembrane system. In a basic loss-of-function electrophysiological screen, we found that the disruption of eight (i.e., Rab5, CG32795, Mpcp, Tom70, Vir-1, CG30427, Eaat1, and CG2781) of 28 randomly selected candidates affects olfactory responses in vivo. Thus, because this Orco interactome includes physiologically meaningful candidates, we anticipate that our platform will help guide further research on the molecular mechanisms of the insect odorant receptor family.

Fenbendazole의 항암활성에서 활성산소종의 관련성 (Involvement of reactive oxygen species in the anti-cancer activity of fenbendazole, a benzimidazole anthelmintic)

  • 한용;주홍구
    • 대한수의학회지
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    • 제60권2호
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    • pp.79-83
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    • 2020
  • Fenbendazole (FBZ) is a benzimidazole anthelmintic that has been widely used in treatments for gastrointestinal parasites including pinworms and roundworms in animals. Recently, some studies demonstrated that FBZ has anti-cancer effects related to disruption of microtubule polymerization. In this study, we investigated whether FBZ has anti-cancer activity in HL-60 cells, a human leukemia cell line, and assessed its relationship with the production of reactive oxygen species (ROS). FBZ treatment at 0.25-1 μM significantly decreased the metabolic activity of HL-60 cells. The mitochondrial membrane potential of FBZ-treated HL-60 cells decreased in a concentration-dependent manner. Apoptosis analysis using annexin V-FITC/propidium iodide staining demonstrated that 1 μM FBZ increased the percentages of cells in apoptosis and necrosis. In addition, Hoechst 33342 staining showed the presence of broken nuclei in HL-60 cells treated with 0.5 and 1 μM FBZ. To investigate the anti-cancer mechanism of FBZ, HL-60 cells were treated with FBZ in the absence or presence of N-acetyl cysteine (NAC), an inhibitor of ROS production. NAC significantly recovered the decreased metabolic activity of HL-60 induced by 0.5 and 1 μM FBZ treatments. This study provides evidence that FBZ has anti-cancer activity in HL-60 cells provided, in part, via ROS production.

A Receiver-Aided Seamless And Smooth Inter-RAT Handover At Layer-2

  • Liu, Bin;Song, Rongfang;Hu, Haifeng
    • KSII Transactions on Internet and Information Systems (TIIS)
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    • 제9권10호
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    • pp.4015-4033
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    • 2015
  • The future mobile networks consist of hyper-dense heterogeneous and small cell networks of same or different radio access technologies (RAT). Integrating mobile networks of different RATs to provide seamless and smooth mobility service will be the target of future mobile converged network. Generally, handover from high-speed networks to low-speed networks faces many challenges from application perspective, such as abrupt bandwidth variation, packet loss, round trip time variation, connection disruption, and transmission blackout. Existing inter-RAT handover solutions cannot solve all the problems at the same time. Based on the high-layer convergence sublayer design, a new receiver-aided soft inter-RAT handover is proposed. This soft handover scheme takes advantage of multihoming ability of multi-mode mobile station (MS) to smooth handover procedure. In addition, handover procedure is seamless and applicable to frequent handover scenarios. The simulation results conducted in UMTS-WiMAX converged network scenario show that: in case of TCP traffics for handover from WiMAX to UMTS, not only handover latency and packet loss are eliminated completely, but also abrupt bandwidth/wireless RTT variation is smoothed. These delightful features make this soft handover scheme be a reasonable candidate of mobility management for future mobile converged networks.

Protective Effect of Right Ventricular Mitochondrial Damage by Cyclosporine A in Monocrotaline-induced Pulmonary Hypertension

  • Lee, Dong Seok;Jung, Yong Wook
    • Korean Circulation Journal
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    • 제48권12호
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    • pp.1135-1144
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    • 2018
  • Background and Objectives: Mitochondria play a key role in the pathophysiology of heart failure and mitochondrial permeability transition pore (MPTP) play a critical role in cell death and a critical target for cardioprotection. The aim of this study was to evaluate the protective effects of cyclosporine A (CsA), one of MPTP blockers, and morphological changes of mitochondria and MPTP related proteins in monocrotaline (MCT) induced pulmonary arterial hypertension (PAH). Methods: Eight weeks old Sprague-Dawley rats were randomized to control, MCT (60 mg/kg) and MCT plus CsA (10 mg/kg/day) treatment groups. Four weeks later, right ventricular hypertrophy (RVH) and morphological changes of right ventricle (RV) were done. Western blot and reverse transcription polymerase chain reaction (RT-PCR) for MPTP related protein were performed. Results: In electron microscopy, CsA treatment prevented MCT-induced mitochondrial disruption of RV. RVH was significantly increased in MCT group compared to that of the controls but RVH was more increased with CsA treatment. Thickened medial wall thickness of pulmonary arteriole in PAH was not changed after CsA treatment. In western blot, caspase-3 was significantly increased in MCT group, and was attenuated in CsA treatment. There were no significant differences in voltage-dependent anion channel, adenine nucleotide translocator 1 and cyclophilin D expression in western blot and RT-PCR between the 3 groups. Conclusions: CsA reduces MCT induced RV mitochondrial damage. Although, MPTP blocking does not reverse pulmonary pathology, it may reduce RV dysfunction in PAH. The results suggest that it could serve as an adjunctive therapy to PAH treatment.