• Title/Summary/Keyword: 독성 발현 기작

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Study of Atmospheric Dry Deposition Fluxes of Heavy Metals (대기 중 입자상 중금속의 건식 침적량에 관한 연구)

  • 윤희정;이승묵;김용표
    • Proceedings of the Korea Air Pollution Research Association Conference
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    • 2001.11a
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    • pp.111-112
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    • 2001
  • 대기로부터 침적된 물질로 인해 토양오염과 수질오염 현상이 심화될 뿐만 아니라 환경 생태계도 영향을 받는다는 것이 밝혀지면서 대기 침적 현상에 대한 관심이 커지고 있다. 침적은 대기 중의 여러 미량 물질들이 환경계에 미치는 영향과 그들의 이동을 조절하는 중요한 기작 중 하나이다. 중금속은 가장 오래전부터 알려진 독성물질로서, 약 30가지 금속이 사람에게 독성을 발현하는 것으로 알려져 있고, 그 중 일부 중금속은 발암성을 가지고 있다. (중략)

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Study on the Mechanism of Manifestation of Ecological Toxicity in Heavy Metal Contaminated Soil Using the Sensing System of Earthworm Movement (지렁이 움직임 감지 시스템을 이용한 중금속 오염 토양의 생태독성 발현 메커니즘에 대한 연구)

  • Lee, Woo-Chun;Lee, Sang-Hun;Jeon, Ji-Hun;Lee, Sang-Woo;Kim, Soon-Oh
    • Economic and Environmental Geology
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    • v.54 no.3
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    • pp.399-408
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    • 2021
  • Natural soil was artificially contaminated with heavy metals (Cd, Pb, and Zn), and the movement of earthworm was characterized in real time using the ViSSET system composed of vibration sensor and the other components. The manifestation mechanism of ecological toxicity of heavy metals was interpreted based on the accumulative frequency of earthworm movement obtained from the real-time monitoring as well as the conventional indices of earthworm behavior, such as the change in body weight before and after tests and biocumulative concentrations of each contaminant. The results showed the difference in the earthworm movement according to the species of heavy metal contaminants. In the case of Cd, the earthworm movement was decreased with increasing its concentration and then tended to be increased. The activity of earthworm was severely increased with increasing Pb concentration, but the movement of earthworm was gradually decreased with increasing Zn concentration. The body weight of earthworm was proved to be greatly decreased in the Zn-contaminated soil, but it was similarly decreased in Cd- and Pb-contaminated soils. The bioaccumulation factor (BAF) was higher in the sequence of Cd > Zn > Pb, and particularly the biocumulative concentration of Pb did not show a clear tendency according to the Pb concentrations in soil. It was speculated that Cd is accumulated as a metallothionein-bound form in the interior of earthworm for a long time. In particular, Cd has a bad influence on the earthworm through the critical effect at its higher concentrations. Pb was likely to reveal its ecotoxicity via skin irritation or injury of sensory organs rather than ingestion pathway. The ecotoxicity of Zn seemed to be manifested by damaging the cell membranes of digestive organs or inordinately activating metabolism. Based on the results of real-time monitoring of earthworm movement, the half maximal effective concentration (EC50) of Pb was estimated to be 751.2 mg/kg, and it was similar to previously-reported ones. The study confirmed that if the conventional indices of earthworm behavior are combined with the results of newly-proposed method, the mechanism of toxicity manifestation of heavy metal contaminants in soils is more clearly interpreted.

Characterization of UV-Inducible Gene (UVI-180) in Schizosaccharomyces pombe (분열형 효모 Schizosaccharomyces pombe에서 자외선 유도유전자 UVI-180의 특성 연구)

  • Park, In-Soon
    • Environmental Analysis Health and Toxicology
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    • v.18 no.3
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    • pp.225-230
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    • 2003
  • 본 연구는 DNA 상해유도기작을 규명하기 위하여 하등 진핵생물인 분열형 효모 Schizosaccharomyces Pombe로부터 subtraction hybridization방법을 이용하여 자외선 유도 유전자인 UVI-180을 분리하고 그 유전자 구조와 발현양상을 조사하였다. UVI-180유전자의 발현양상을 Northern hybridization 방법으로 살펴본 결과 자외선(ultraviolet-light)조사 1시간 후에 최대의 발현 증가를 나타내었다. 반면 알킬화제인 MMS(methyl methanesulfonate)처리에 의해서는 전혀 발현이 증가되지 않았다. 이 결과 UVI-180유전자는 DNA상해에 따라 각기 다른 발현양상을 나타냄을 알 수 있었다. 유전자의 기능을 알기 위하여 null-mutant세포 주를 제조하여 그 특성을 살펴본 결과 이 유전자는 세포의 성장에 필수적인 유전자임을 알 수 있었다.

Isolation and Characterization of UV-Inducible Gene UV150 and UV200 in Eukaryotic Cells (진핵세포에서 DNA 상해에 반응하는 유전자 (UV150과 UV200) 기능연구 분리 및 특성 연구)

  • Choi In-Soon
    • Environmental Analysis Health and Toxicology
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    • v.21 no.1 s.52
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    • pp.21-26
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    • 2006
  • 본 연구는 DNA 상해유도기작을 규명하기 위하여 하등 진핵생물인 분열형 효모 Schizosaccharomyces pombe로부터 subtraction hybridization방법을 이용하여 자외선 유도 유전자인 UV150과 UV200을 분리하고 그 유전자 구조와 발현양상을 조사하였다. 분리한 유전자의 발현양상을 Northern hybridization 방법으로 살펴본 결과 자외선 조사 1시간 후부터 발현이 증가되었다. 또한 알킬화제인 Methyl Methanesulfonate (MMS) 처리에 의해서도 발현이 증가되었다. 이 결과 다른 UV-inducible유전자와는 다르게 분리한 UV150유전자는 UV에 UV200유전자는 MMS에 의하여 발현이 증가됨을 알 수 있었다. 유전자의 기능을 알기 위하여 URA4 유전자를 이용하여 null-mutant 세포주를 제조하여 그 특성을 살펴본 결과 분리한 UV150 유전자는 세포의 성장에 필수적인 유전자임을 알 수 있었다.

Effects of Fenvalerate on Apoptosis Level and GFAP Expression in the Brain Tissue of the Pale Chub (Pisces: Zacco platypus) (Fenvalerate가 피라미(Zacco platypus) 뇌 조직에서 apoptosis 정도와 GFAP 발현에 미치는 영향)

  • Kim, Sung-Woo;Park, No-Kwan;Lee, Sang-Rae;Reu, Dong-Suck
    • Applied Microscopy
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    • v.42 no.2
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    • pp.53-59
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    • 2012
  • We evaluated the level of toxicity by LC50 and investigated the mechanism of brain impairment and GFAP expression by light and fluorescence microscopes in the pale chub, Zacco platypus, treated with fenvalerate. Survival rate was decreased according to the rise of fenvalerate concentration, and LC50 concentration was $27.79{\mu}g/L$. Apoptosis was increased according to the rise of fenvalerate concentration by TUNEL assay which determine apoptotic cell death population. Also, GFAP expression was increased in the periventricular zone. These results suggest that apoptosis might be a major mechanism to brain impairment of the pale chub by fenvalrerate. Increased GFAP expression in the periventricular zone would be an index of brain impairment. Taken together, this study might contribute to reveal the pathological mechanism of fish brain impairment by insecticide of pyrethroid, and to be an useful basic data for preservation of aquatic ecosystem.

Mechanism of Apoptosis Induced by Spermine in MCF-7 Breast Cancer Cells (MCF-7 유방암 세포주에 있어서 spermine에 의해 유도된 세포사멸 기작)

  • Jang, Eun-Seong;Kim, Byeong-Gee
    • Journal of Life Science
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    • v.18 no.9
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    • pp.1177-1185
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    • 2008
  • In the present work, we show that spermine (spm)-induced cytotoxicity is due to the mitochondrial-dependent pathway triggered by the intracellular $Ca^{2+}$ increase in MCF-7 human breast cancer cells. Spm induced the intracellular $Ca^{2+}$ increase in a dose-dependent manner in the medium containing 1.5 mM $Ca^{2+}$. Even in the $Ca^{2+}$-free medium, spm could induce a minor $Ca^{2+}$ increase in a dose-dependent fashion, suggesting a probable leak from the internal storage. The cytotoxic effect of $Ca^{2+}$ could be further proved by using either BAPTA or ionophore. Spm-induced $Ca^{2+}$ increase led to the release of cytochrome c from mitochondria into the cytosol and the change of mitochondrial membrane potential. In MCF-7 cells, caspase-7 plays a key role in the downstream of apoptosis because caspase-3 is absent. In the cells treated with spm, the cleavage of caspase-7 and -12 was increased almost two-fold. The level of anti-apoptotic Bcl-2 protein decreased to 35% of the control; however, the cells showed increased expression of pro-apoptotic Bax protein about two-fold in response to spm. These results imply that the apoptotic signaling pathway activated by spm is likely to be mediated via the mitochondrial-dependent pathway.

식물추출물에 의한 벼 도열병균(Magnaprothe oryzae)의 ABC transporter발현 억제 및 포장에서의 방제

  • Ju, Myeong-Ho;Yeo, Yu-Mi;Choe, Pil-Seon;;Yang, Gwang-Yeol;Lee, Yeong-Jin
    • Proceedings of the Plant Resources Society of Korea Conference
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    • 2019.04a
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    • pp.37-37
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    • 2019
  • 벼 재배포장에서 화학약제의 반복적인 사용으로 인한 병원균의 약제내성과 환경오염은 커다란 문제가 되고 있다. 이러한 약제내성을 극복하기 위한 노력의 하나로 유전자수준의 약제내성기작의 규명과 대체물질의 발굴이 필요하다고 사료된다. 이에 본 연구에서는 식물종이 지니는 광범위한 다양성에 주목하였고, 700여 종의 식물추출물을 벼 도열병균에 처리해 균사성장억제효과를 조사하는 선별실험을 실시하였고, 영릉향과 지모추출물이 높은 균사성장억제효과를 보이는 것을 확인했다. 영릉향과 지모 추출물이 화학약제를 대체하는 대안물질로서 가능성을 조사하기위해 균사성장억제능력 확인실험, 분획, HPLC (High Performance Liquid Chromatography), 포자발아 및 부착기 형성확인검정, ABC transporter의 발현조사, 환경독성실험등을 실시했다. 실험 결과, 영릉향과 지모 추출물을 벼 도열병균에 처리하였을 때 약제저항성유전자 ABC transporter의 기능이 저하되고 화학약제에 대한 내성이 감소를 확인했으며, 분획과 HPLC분석을 통해 영릉향과 지모의 유효성분을 확인했다. 또한, 실제 포장에서 영릉향 추출물과 지모 추출물을 사용하여 벼 도열병 방제가를 확인하는 포장시험을 실시한 결과, 각각 63%와 62%의 목 도열병 방제가를 확인 하였으며, 인축환경에 대한 유해성을 조사하기 위해 어류, 설치류, 중치류, 곤충을 대상으로 영릉향 추출물을 처리해 급성독성시험 실시한 결과, 고농도의 투여량에서도 독성이 없는 것을 확인했다. 위의 실험 결과를 토대로, 영릉향과 지모추출물이 화학농약에 의한 환경오염을 막을 수 있고, 인축과 환경에 피해를 입히지 않는 친환경자재로 친환경적인 생물농약의 신소재로서 가능성을 나타냈다고 사료된다.

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Anti-adipogenic Effect of Undaria pinnatifida Extracts by Ethanol in 3T3-L1 Adipocytes (미역 에탄올 추출물이 지방세포 형성과정에 미치는 영향)

  • Kim, Hye-Jin;Kang, Chang-Han;Kim, Sung-Koo
    • Journal of Life Science
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    • v.22 no.8
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    • pp.1052-1056
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    • 2012
  • Undaria pinnatifada has been used as a natural diet food with few calories and as a source of iodine. Even though U. pinnatifida has been regarded as a diet food, the mechanisms of its inhibitory effects on adipocyte differentiation and the accumulation of fat in adipocytes are poorly understood. In this study, the effect and mechanism of U. pinnatifida ethanol extract on 3T3-L1 differentiation into adipocytes were investigated. The effects of U. pinnatifida ethanol extract on cell viability and the anti-adipogenic effect were investigated via MTT assay, Oil red O staining, RT-PCR, and western blot. The U. pinnatifida ethanol extract did not show toxicity up to a concentration of 50 ${\mu}g/ml$. The addition of U. pinnatifida ethanol extract decreased triglyceride contents by 40% when 50 ${\mu}g/ml$ of U. pinnatifida ethanol extract was added during 3T3-L1 differentiation and adipocyte triglyceride formation. The transcription and expression of peroxisome proliferator-activated receptor ${\gamma}$ ($PPAR{\gamma}$), leptin, and hormone-sensitive lipase (HSL) as adipocyte-specific proteins were determined by RT-PCR and western blot. The overexpression of $PPAR{\gamma}$ could accelerate adipocyte differentiation. Also, leptin was secreted for triglyceride accumulation in the adipocytes and the increase of adipocyte cell size. Thus, $PPAR{\gamma}$ and leptin were used as indicators of obesity. $PPAR{\gamma}$ and leptin were repressed by the increased addition of U. pinnatifida ethanol extract. This indicates that U. pinnatifida was effective as an anti-obesity agent by repressing the differentiation of 3T3-L1 into adipocytes and inhibiting triglyceride formation in adipocytes.

Induction of NADPH oxidases and antioxidant proteins by Porphyromonas gingivalis in KB cells (Porphyromonas gingivalis 감염된 구강상피세포에서 NADPH oxidase와 항산화단백의 발현)

  • Kim, Min-Jeong;Chung, Hyun-Ju;Park, Byung-Ju;Park, Hae-Ryoung;Lee, Tae-Hun
    • Journal of Periodontal and Implant Science
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    • v.36 no.4
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    • pp.863-878
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    • 2006
  • Porphyromonas gingivalis는 치주질환을 야기하는 독성세균으로서, 구강상피세포에 p. gingivalis가 감염되었을 때, 세포형태에 변화를 초래함으로 인해 방어기작이 작동하게 된다. 치주질환과 관련되어 생성된 활성 산소종의 소거에 관여하는 항산화성분은 p. gingivalis 이 감염된 구강상피세포에서 그 분포와 발현수준이 달라지리라 예상된다. 따라서 이번 연구에서는 구강상피세포(KB 세포)에 p. gingivalis가 감염되었을 때 야기되는 활성산소종과 이를 소거하는 역할을 하는 항산화단백들의 역할들을 규명하고자 하였다. 활성산소종 형성을 조절하는 NADPH oxidase 중 NOX4와 Rac1 전사체는 구강상피세포에서 p. gingivalis세균에 의해 증가하였으며 $gp91^{phox}$, Rac2, $p47^{phox}$$p67^{phox}$는 세균에 의한 변화가 관찰되지 않았다. 반면에 $p40^{phox}$ 전사체는 감소하는 경향을 보였다. NOX1 전사체는 p. gingivalis 처리 30분 후 감소하였다가 60분 후에는 다시 증가하는 양상을 보였다. 같은 시간에 NOX 활성화 단백인 NOXA1은 감소하고, NOX 구성단백질인 NOXO1은 증가하는 경향을 보였다. p. gingivalis가 감염된 구강상피세포를 방어하는 항산화단백 발현수준을 평가한 결과, SOD1, 2, 3 모두 p. gingivalis 처리시간에 따라 증가하는 양상을 보였다. GPx 발현 양상도 SOD와 유사하게 나타났다. $H_2O_2$를 소거하는 Prx는 감염된 KB 세포에서 Prx4와 Prx5가 4-6배 증가하는 것을 알 수 있었다. 반면 endocytosis 과정 중 $H_2O_2$ 생산은 변화되지 않았다. 이번 연구의 결과, p. gingivalis의 감염은 KB 세포의 NOX4와 Rac1의 NADPH oxidase 발현을 증가시켰으며, NOX1은 NOXA1과 NOXO1의 조절에 의해 영향을 받음을 알 수 있었다. 또한 항산화기작으로는 SOD, GPx, Prx가 증가하였는데, 이것은 Prx4와 Prx5가 중요한 역할을 할 것을 시사하였다.

Effects of Mifepristone and Tamoxifen on Calcium Modulation in DU-145 Prostate Cancer Cells (DU-145 전립선 암세포에 있어서 mifepristone과 tamoxifen이 칼슘조절에 미치는 영향)

  • Kim, Yeo-Reum;Kim, Byeong-Gee
    • Journal of Life Science
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    • v.20 no.9
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    • pp.1324-1331
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    • 2010
  • Mifepristone (MIF) and Tamoxifen (TAM) have been used in the treatment of prostate cancer and breast cancer for more than a decade. MIF can induce apoptosis in both AR-positive and negative prostate cancer cells. Because of its pleiotropic ligand-receptor properties, TAM exerts cytotoxic activity in estrogen (ER)-positive and various ER.negative cancer cells. However, the molecular mechanisms of these two substances are not yet clear. In the present work, we report that the cytotoxic effects of MIF and TAM are due to the modulation of intracellular $Ca^{2+}$ level in DU-145, androgen-insensitive cells. When the cells were treated with micromolar concentrations of either MIF or TAM, the growth and viability were significantly decreased in a dose- and time-dependent manner. The apoptosis induced by MIF or TAM was further proved and analyzed by confocal laser scanning microscopy (CLSM) and fluorescence-activated cell sorting (FACS). In the cells cultivated in a normal 1.5 mM $Ca^{2+}$ medium, both MIF and TAM also induced an increase of the intracellular $Ca^{2+}$ level in a dose-dependent fashion. Since a change in calcium level could not be found in cells of the $Ca^{2+}$-free medium, the increase of intracellular $Ca^{2+}$ level might be due to an increase in extracellular calcium uptake. Our results show that the apoptotic effect was more prominent in TAM treatment compared to MIF treatment in DU-145 cells. The above findings might be due to the difference in the uppermost pathways of apoptosis induced by either MIF or TAM. When we checked the level of procaspase-8 activation, TAM showed minor level of activation, as opposed to MIF, which exerted strong activation. In both treatments, the levels of anti-apoptotic protein Bcl-2 decreased, and pro-apoptotic protein Bax level increased more than 2-fold. The activation of caspase-3, a key protease enzyme in the downstream pathway of apoptosis, was much higher in the cells treated with TAM, compared to the MIF treatment. The overall apoptotic activity shown in the present work was closely related to intracellular $Ca^{2+}$ concentration levels. Therefore, the cytotoxic activity induced by MIF and TAM might have been due to intracellular calcium modulation.