• 제목/요약/키워드: 독성 발현 기작

검색결과 46건 처리시간 0.049초

Neuroprotective Effects of Parkin and Bcl-2 against Dieldrin-induced Endoplasmic Reticulum Stress (디엘드린 유도성 소포체 스트레스에서의 parkin과 Bcl-2의 신경보호 효과)

  • Seo, Jeong-Yeon;Kim, Jae-Sung;Kim, Do Kyung;Chun, Hong Sung
    • Journal of Life Science
    • /
    • 제32권10호
    • /
    • pp.771-777
    • /
    • 2022
  • Dopaminergic (DA) cell death in Parkinson's disease (PD) has been attributed to multiple, distinct genetic and environmental factors. In rare familial PD loss of parkin function mutations play a key role in nigral DA neuron-specific pathogenesis primarily via endoplasmic reticulum (ER) stress. In more prevalent sporadic PD, environmental exposure to pesticides has a significant epidemiological role. However, it is largely unknown how environmental exposure to xenobiotics is etiologically linked with the known etiology in familial PD. In the present study biochemical evidence for a common pathogenic mechanism between sporadic and familial PD has been identified employing the recently characterized mesencephalic DA cell line, N27-A. Dieldrin, an organochlorine pesticide epidemiologically implicated in sporadic PD, induced the markers of ER stress response such as a chaperone BiP/Grp78, heme oxygenase-1 and especially, parkin. Accordingly, dieldrin activated the ER resident Caspase-12, a mediator of ER stress-specific apoptosis, during cell death of N27-A cells. Of great interest the dieldrin-induced DA neuronal cell death was synergistically rescued by the overexpression of ER resident neuroprotective proteins, parkin and Bcl-2. The present findings implicate that accumulation of ER stress could be one of common pathogenic mechanisms in idiopathic and familial PD, and some ER proteins, such as parkin and Bcl-2 may effectively attenuate ER stress-mediated N27-A DA cell death.

Can Hinokitiol Kill Cancer Cells? Alternative Therapeutic Anticancer Agent via Autophagy and Apoptosis (Hinokitiol에 의해 유도된 Autophagy 및 Apoptosis에 의한 대체 항암요법 연구)

  • Lee, Tae Bok;Jun, Jin Hyun
    • Korean Journal of Clinical Laboratory Science
    • /
    • 제51권2호
    • /
    • pp.221-234
    • /
    • 2019
  • Cancer is genetically, metabolically and infectiously induced life threatening disorder showing aggressive growing pattern with invasive tendency. In order to prevent this global menace from jeopardizing human life, enormous studies on carcinogenesis and treatment for chemotherapy resistance have been intensively researched. Hinokitiol (${\beta}$-thujaplicin) extracted from heart wood of cupressaceous is a well-known bioactive compound demonstrating anti-inflammation, anti-bacteria and anti-cancer effects on several cancer types via apoptosis and autophagy. This study proposed that hinokitiol activates transcription factor EB (TFEB) nuclear translocation for autophagy and lysosomal biogenesis regardless of nutrient condition in cancer cells. Mitophagy and ${\beta}$-catenin translocation into the nucleus under treatment of hinokitiol on non-small cell lung cancer (NSCLC) cells and HeLa cells were investigated. Hinokitiol exerted cytotoxicity on HeLa and HCC827 cells; moreover, artificially induced autophagy by overexpression of TFEB granted imperfect sustainability onto HeLa cells. Taken together, hinokitiol is the prominent autophagy inducer and activator of TFEB nuclear translocation. Alternative cancer therapy via autophagy is pros and cons since the autophagy in cancer cells is related to prevention and survival mechanism depending on nutrition. To avoid paradox of autophagy in cancer therapy, fine-tuned regulation and application of hinokitiol in due course for successful suppressing cancer cells are recommended.

Enhancement of Skin Immune Activation Effect of Collagen Peptides Isolated from Asterias amurensis (불가사리 유래 콜라겐 펩타이드의 피부 면역 증진 효과)

  • Jeong, Hyang-Suk;Kwon, Min-Chul;Han, Jae-Gun;Ha, Ji-Hye;Jin, Ling;Kim, Jin-Chul;Kwak, Hyeong-Geun;Hwang, Bo-Young;Lee, Hyeon-Yong
    • Korean Journal of Food Science and Technology
    • /
    • 제40권5호
    • /
    • pp.522-527
    • /
    • 2008
  • Low molecular peptides were isolated from Asterias amurensis via SDS-PAGE. The peptides were separated via consecutive gel filtration as five fractions (F1-F5) according to molecular weights, based on the results of MALDI-TOF MS analysis. The molecular weight of the most active peptide was estimated as 15,000 daltons. The peptide showed cytotoxicity on normal human fibroblast cells at levels as low as 20% when 1.0 mg/mL of the samples was added. The peptide also exhibited higher levels of nitric oxide production from macrophages than the lipopolysaccaharides. It was determined that prostaglendin $E_2$ production was significantly inhibited, up to 127.8% as compared to the control. The low molecular peptide inhibited hyaluronidase activity as 535.7 ${\mu}g/mL$ of $IC_{50}$. It can be concluded that the relatively low molecular weight peptide, fucoidan, from A. amurensis has excellent cosmetic and immunomodulatory activities, which can be considered as a possible resource of new cosmetic agents for skin immunomodulation.

Apoptotic Effect of Rubia cordifolia Dichloromethane Extracts on Human Acute Jurkat T Cells (천초근 dichloromethane 추출물의 Jurkat T 세포에서 세포사멸 효과)

  • Kim, Ji-Hye;Lee, Jong-Hwan;Kim, Young-Ho;Kim, Kwang-Hyeon
    • Journal of Life Science
    • /
    • 제19권2호
    • /
    • pp.163-168
    • /
    • 2009
  • To understand cytotoxic activity of Rubia cordifolia L. (Rubiaceae), which has been used as a traditional oriental medicine, the mechanism underlying cytotoxic effect of its extract on human acute Jurkat T cells was investigated. The methanol extract of roots (3 kg) of R. codifolia was evaporated, dissolved in water, and then extracted by dichloromethane. The substances in the chloroform extract showing the most cytotoxic activity were further purified by a series of preparative HPLC. The extracted active substance (65 mg) was designated as CCH1. When Jurkat T cells were treated with CCH1 at concentration ranging from 0.5 to 2.0 ${\mu}g$/ml, apoptotic phenomena of cells companying several subsequent biochemical reactions such as mitochondria cytochrome c release, activation of casapase-8, -9, and caspase- 3, degradation of PARP and DNA fragmentation occurred via mitochondria-dependent pathway. However, abrogation of apoptosis was observed in an ectopic expression of Bcl-xL, which is a suppressor for mitochondrial cytochrome c release. These results demonstrate that the cytotoxicity of CCH1 against Jurkat T cells is attributable to apoptosis mediated by mitochodria-dependent death-signaling regulated by Bcl-xL. In addition, the CCH1 is more potent to leukemia Jurkat T cell than to human peripheral blood monocyte cells (PBMC).

Optimal Extract Condition for the Enhancement of Anticancer Activities of Artemisia princeps Pampanini (강화 사자발쑥의 항암활성 증진을 위한 추출조건의 최적화)

  • Kwon, Min-Chul;Kim, Cheol-Hee;Kim, Hyou-Sung;Lee, Sang-Hee;Chio, Geun-Pyo;Park, Uk-Yeon;You, Sang-Guan;Lee, Hyeon-Young
    • Korean Journal of Medicinal Crop Science
    • /
    • 제15권4호
    • /
    • pp.233-240
    • /
    • 2007
  • Extractions of Artemisia princeps Pampanini were obtained by using water and ethanol at different temperatures ($60^{\circ}C,\;100^{\circ}C$) with or without ultrasonification process (40 kHz). Yield of ultrasonificated extracts were about 20% higher than that of control group. Cytotoxicity of all conditions through adding 1.0 mg/$m{\ell}$ was below 37%, and treated with ultrasonification group was lower than the other group, about $5{\sim}8%$. $100^{\circ}C$ water extract with ultrasonification was higher anticancer activities as maximum 73% and higher selectivities at concentrations over 0.8 mg/$m{\ell}$. The extracts treated with ultrasonification were higher anticancer activities than the control. Densitometric analysis of bcl-2 revealed that extracts of high anticancer activity had low density. This results suggest that expression of bcl-2 protein by adding of Artemisia princeps Pampanini extracts relative to taking cancer. To conclude, optimum condition for efficient extraction of Artemisia princeps Pampanini is using water with ultrasonification at over $60^{\circ}C$ below $100^{\circ}C$.

Prediction and Annotation of ABC Transporter Genes from Magnaporthe oryzae Genome Sequence (벼도열병균 게놈서열로부터 ABC transporter 유전자군의 예측 및 특성 분석)

  • Kim, Yong-Nam;Kim, Jin-Soo;Kim, Su-Young;Kim, Jeong-Hwan;Lee, Jong-Hwan;Choi, Woo-Bong
    • Journal of Life Science
    • /
    • 제20권2호
    • /
    • pp.176-182
    • /
    • 2010
  • Magnaporthe oryzae is destructive plant-pathogenic fungus and causes rice blast. The pathogen uses several mechanisms to circumvent the inhibitory actions of fungicides. ATP-binding cassette (ABC) transporters are known to provide protection against toxic compounds in the environment. PC facilitated bioinformatic analysis, particularly with respect to accessing and extracting database information and domain identification. We predicted ABC transporter genes from the M. oryzae genome sequence with computation and bioinformatics tools. A total of thirty three genes were predicted to encode ABC transporters. Three of thirty three putative genes corresponded to three known ABC transporter genes (ABC1, ABC2 and ABC3). Copy numbers of the ABC transporter genes were proven by Southern blot analysis, which revealed that twenty genes tested exist as a single copy. We amplified the DNA complementary to RNA corresponding to eleven of these by reverse transcriptase polymerase chain reaction.

Immunostimulatory activity and intracellular signaling pathways of a rhamnogalcaturonan II polysaccharide isolated from ginseng berry (인삼열매로부터 분리한 Rhamnogalacturonan II 다당의 면역활성과 세포 내 신호전달 기작 규명)

  • Cha, Ha Young;Son, Seung-U;Shin, Kwang-Soon
    • Korean Journal of Food Science and Technology
    • /
    • 제53권6호
    • /
    • pp.722-730
    • /
    • 2021
  • In this study, we aimed to elucidate the intracellular signaling pathways for macrophage activation by the polysaccharide GBW-II purified from ginseng berry. GBW-II consists of 14 different sugars, including rarely observed sugars such as 2-O-methyl-xylose, apiose, aceric acid, 2-keto-3-deoxy-D-manno-2-octulosonic acid, and 2-keto-3-deoxy-D-lyxo-2-heptulosaric acid, which are typical RG-II component sugars. GBW-II enhanced the production of IL-6 and TNF-α in RAW 264.7 cells. In experiments evaluating specific inhibitor activity, it was found that the production of IL-6 was suppressed by inhibitors of SB, PD, and BAY, and the production of TNF-α was suppressed by PD and BAY. The experiments with neutralizing antibodies showed that TLR4 was involved in the stimulation of IL-6 production by GBW-II in RAW 264.7 cells, whereas TNF-α production was regulated through SR and TLR2. These results suggest that GBW-II activates the MAPK and NF-κB pathways via several macrophage receptors, including SR, TLR2, and TLR4, and subsequently induces the secretion of IL-6 and TNF-α.

A study of the lipoprotein lipase inhibitory mechanism of Poncirus trifoliata water extracts (탱자 (Poncirus trifoliata)의 lipoprotein lipase 억제메커니즘)

  • Lee, Sung Mee;Kang, Yun Hwan;Kim, Kyoung Kon;Kim, Tae Woo;Choe, Myeon
    • Journal of Nutrition and Health
    • /
    • 제48권1호
    • /
    • pp.9-18
    • /
    • 2015
  • Purpose: Poncirus trifoliata has been reported to have anti-inflammatory, antioxidant, and immune activities. However, its anti-obesity activity and the mechanism by which the water extract of dried, immature fruit of Poncirus trifoliata (PF-W) acts are not clear. This study suggests a potential mechanism associated with the anti-obesity activity of PF-W. Methods: We measured the effect of PF-W on lipoprotein lipase (LPL) regulation using enzyme-linked immunosorbent assay (ELISA) and an activity assay. The LPL regulation mechanism was examined by reverse transcription polymerase chain reaction (RT-PCR) to measure the mRNA expression of biomarkers related to protein transport and by western blot for analysis of the protein expression of the transcription factor CCAAT-enhancer-binding protein ($C/EBP{\beta}$). Results: The total polyphenol and flavonoid content of PF-W was $52.15{\pm}4.02$ and $6.56{\pm}0.47mg/g$, respectively. PF-W treatment decreased LPL content in media to $58{\pm}5%$ of that in control adipocyte media, and increased LPL content to $117{\pm}3.5%$ of that in control adipocytes, but did not affect the mRNA expression of LPL. PF-W also increased the mRNA expression of sortilin-related receptor (SorLA), a receptor that induces endocytosis and intracellular trafficking of LPL, in a concentration- and time-dependent manner. Finally, cell fractionation revealed that PF-W treatment induced the expression of $C/EBP{\beta}$, a SorLA transcription factor, in the nuclei of 3T3-L1 adipocytes. Conclusion: The LPL secretion and activity assay showed PF-W to be an LPL secretion inhibitor, and these results suggest the potential mechanism of PF-W involving inhibition of LPL secretion through $C/EBP{\beta}$-mediated induction of SorLA expression.

Effects of Vitexin from Mung Bean on 3T3-L1 Adipocyte Differentiation and Regulation According to Adipocytokine Secretion (녹두의 Vitexin이 비만전구세포에서 세포분화 및 아디포사이토카인 분비능에 미치는 영향)

  • Wi, Hae-Ri;Choi, Mun-Ji;Choi, Se-Lim;Kim, Ae-Jung;Lee, Myoung-Sook
    • Journal of the Korean Society of Food Science and Nutrition
    • /
    • 제41권8호
    • /
    • pp.1079-1085
    • /
    • 2012
  • Obesity is an important issue worldwide as it may associated with increased prevalence of metabolic diseases. Mung bean is known as a functional food for decreasing the glycemic index and lipid profile of plasma. The purpose of this study was to investigate the anti-obesity effects of vitexin from mung bean on the regulation of adipocyte differentiation and adipocytokine secretion. When 3T3-L1 adipocytes were treated with vitexin from days 0 to 14 at various levels of 25, 50, 100, and $200{\mu}M$, there was no change in cell viability. Vitexin treatment at 50, 100, and $200{\mu}M$ decreased triacylglycerol levels in cells, but only $100{\mu}M$ vitexin induced lipolysis. At $200{\mu}M$ of vitexin, phosphorylation of p38 and ERK, which causes secretion of inflammatory adipocytokines, was depressed, whereas there was an increase in expression of $PPAR{\gamma}$, the key regulator of adipocyte differentiation. Phosphorylation of AMPK increased at $100{\mu}M$ vitexin. TNF-${\alpha}$ and aP2 mRNA expression increased at $25{\mu}M$ vitexin, whereas only TNF-${\alpha}$ mRNA expression increased at $200{\mu}M$ vitexin. Further, the mRNA levels of TNF-${\alpha}$ and aP2 decreased at other concentrations in a dose-dependent manner. Since we observed that mRNA expression of C/EBP, SREBP1, and $PPAR{\gamma}$ did not change upon vitexin treatment, our future studies will investigate other genes such as mTOR, which is related with apoptosis signaling, or SIRT1, which is associated with inhibition of adipogenesis. Our results indicate that vitexin at concentrations between 100 and $200{\mu}M$ is suitable in vivo for the development of mung bean as an anti-obesity therapy or functional food.

Inhibition of Acetylcholinesterase and Butyrylcholinesterase by Phosalone via Bioactivation (Phosalone의 활성화과정을 통한 acetylcholinesterase와 butyrylcholinesterase에 대한 활성 저해)

  • Lim, Geum-Choon;Han, Dae-Sung;Hur, Jang-Hyun
    • Applied Biological Chemistry
    • /
    • 제38권2호
    • /
    • pp.174-178
    • /
    • 1995
  • The purpose of this study was to investigate a role of cytochrome $P_{450}$, for the toxicity of the phosalone in in vitro and in vivo bioactivation systems. The bimolecular inhibition rate constants$(k_i)$ of the phosalone to acetylcholinesterase(AChE) and butyrylcholinesterase(BuChE) were approximately $10^2M^{-1}{\cdot}min^{-1}$, respectively, which meant a poor inhibitor. The potency of the phosalone as an inhibitor of AChE and BuChE was increased about 300 and 40 fold, respectively, when the inhibitor and the ChE were incubated with microsomes fortified with NADPH compared with microsome alone. Piperonyl butoxide(PB) addition to these coupled systems greatly reduced the inhibition of both target enzymes by blocking a bioactivation process. The $I_{50}$ value of the Phosalone alone for rat brain AChE was 170 mg/kg. When PB was pretreated, that value was altered to 42.5 mg/kg. PB pretreatment synergized the inhibition of brain AChE with four times. Rat blood erythrocyte AChE and plasma BuChE were similarly inhibited in vivo by the phosalone and PB pretreatment didn't affect significantly the pattern of the inhibition. The in vivo studies showed different results in the role of cytochrome $P_{450}$ from those of the in vitro studies.

  • PDF