• Title/Summary/Keyword: toxin inhibition

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Relationships between Structural Features and Biological Activities of HC-toxin

  • Kim, Shin-Duk
    • BMB Reports
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    • v.28 no.3
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    • pp.227-231
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    • 1995
  • In order to figure out the relationships between structural features and biological activity of the host-specific HC-toxin in maize, structurally related cyclic tetrapeptides, chlamydocin and CYL-2 were isolated, and their biological activities in maize were examined. Biological activities of preparations were determined by root growth inhibition and electrolyte leakage bioassays. Chlamydocin and CYL-2 showed toxicities to maize. However, the toxicities of these compounds were non-specific. Thus, the precise peptide ring structure of HC-toxin apparently does not play an important role in toxicity, while resistance of maize to HC-toxin is based on a precise ring conformation.

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Separation and Purification of two toxins produced by H. sativum P. K. & B. (H. sativum이 생성(生成)하는 식물(植物) 독소물질 분리(分離))

  • Lee, Sang-Sun;Vick, Brady A.;Stack, Robert W.
    • The Korean Journal of Mycology
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    • v.16 no.1
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    • pp.9-15
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    • 1988
  • Two kinds of toxins were demonstrated in the culture filtrate of H. sativum, and were called 'M' and 'D' toxins. The lettuce bioassay indicated that D-toxin caused less root growth inhibition than M-toxin. Chemical analysis indicated that M-toxin was a very unusual small peptide. D-toxin was shown to have chemical characteristics similar to helminthosporal based on ultraviolet, proton nuclear magnetic resonance and mass spectra. D-toxin was composed of at least two isomers.

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Effect of T-2 Toxin on the Mitogen-Induced Blastogenesis in Chick Splenic Cell (T-2 Toxin이 병아리 비장세포의 유전질 발생에 미치는 영향)

  • Chun, Hyang-Sook;Chung, Duck-Hwa;Lee, Su-Rae
    • Korean Journal of Food Science and Technology
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    • v.26 no.5
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    • pp.585-589
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    • 1994
  • The effects of T-2 toxin on mitogen-induced blastogenesis of chick splenic cells were investigated. The [$^3H$] thymidine incorporation in splenic cells stimulated by lipopolysaccharide and concanavalin A were equally inhibited as the concentration of T-2 toxin was increased. The effective dose of T-2 toxin causing a 50% reduction of [$^3H$] thymidine incorporation was inbetween 1.0 and 5.0 ng/ml for both mitogens. Mitogen-induced blastogenesis in chick splenic cells showed differences among experimental groups with different exposure time of T-2 toxin, exhibiting the most inhibition in the experimental group exposed to T-2 toxin at both embryonic and chick periods.

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Snake Venom synergized Cytotoxic Effect of Natural Killer Cells on NCI H358 Human Lung Cancer Cell Growth through Induction of Apoptosis

  • Oh, Jae Woo;Song, Ho Sueb
    • Journal of Acupuncture Research
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    • v.33 no.2
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    • pp.1-9
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    • 2016
  • Objectives : I investigated whether snake venom can synergistically strengthen the cytotoxic effects of NK-92 cells, and enhance the inhibition of the growth of lung cancer cells including NCI-H358 through the induction of death receptor dependent extrinsic apoptosis. Methods : Snake venom toxin inhibited cell growth of NCI-H358 Cells and exerted non influence on NK-92 cell viability. Moreover, when they were co-cultured with NK cells and concomitantly treated with $4{\mu}g/m{\ell}$ of snake venom toxin, more influence was exerted on the inhibition of growth of NCI-H358 cells than BV or NK cell co-culture alone. Results : The expression of Fas, TNFR2 and DR3 and in NCI-H358 lung cancer cells was significantly increased by co-culture of NK-92 cells and treatment of $4{\mu}g/m{\ell}$ of snake venom toxin, compared to co-culture of NK-92 cells alone. Coincidentally, Bax, caspase-3 and caspase-8 - expressions of pro-apoptotic proteins in the extrinsic apoptosis pathway, demonstrated significant increase. However, in anti-apoptotic NF-${\kappa}B$ activities, activity of the signal molecule was significantly decreased by co-culture of NK-92 cells and treatment of $4{\mu}g/m{\ell}$ of snake venom toxin, compared to co-culture of NK-92 cells or snake venom toxin treated by NCIH358 alone. Meanwhile, in terms of NO generation, there is a significant increase, in co-culture of NK-92 cells with NCI-H358 cells as well as the co-culture of NK-92 cells and concomitant treatment of $4{\mu}g/m{\ell}$ of snake venom toxin. However, no synergistic increase of NO generation was shown in co-culture of NK-92 cells and treatment of $4{\mu}g/m{\ell}$ of snake venom toxin, compared to co-culture of NK-92 cells with NCI-H358 cells. Conclusion : Consequently, this data provides that snake venom toxin could be useful candidate compounds to suppress lung cancer growth along with the cytotoxic effect of NK-92 cells through extrinsic apoptosis.

Clostridium difficile Toxin A Inhibits Wnt Signaling Pathway in Gut Epithelial Cells (대장상피세포 속 Wnt 신호 경로에 대한 C. difficile 톡신A의 영향)

  • Yoon, I Na;Kim, Ho
    • Journal of Life Science
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    • v.28 no.9
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    • pp.1016-1021
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    • 2018
  • Clostridium difficile toxin A causes pseudomembranous colitis. The pathogenesis of toxin A-induced colonic inflammation includes toxin A-dependent epithelial cell apoptosis, resulting in the loss of barrier function provided by epithelial cells against luminal pathogens. Toxin A-dependent epithelial cell apoptosis has been linked to toxin A-induced production of reaction oxygen species and subsequent p38MAPK activation; $p21^{CIP1/WAF1}$ upregulation-dependent cell cycle arrest; cytoskeletal disaggregation; and/or the induction of Fas ligand on epithelial cells. However, the molecular mechanisms underlying toxin A-induced apoptosis remain poorly understood. This study tested whether toxin A could block the Wnt signaling pathway, which is involved in gut epithelial cell proliferation, differentiation and antiapoptotic progression. Toxin A treatment of nontransformed human colonocytes (NCM460) rapidly reduced ${\beta}$-catenin protein, an essential component of the Wnt signaling pathway. Exposure of mouse ileum to toxin A also significantly reduced ${\beta}$-catenin protein levels. MG132 inhibition of proteasome-dependent protein degradation resulted in the recovery of toxin A-mediated reduction of ${\beta}$-catenin, indicating that toxin A may activate intracellular processes, such as $GSK3{\beta}$, to promote degradation of ${\beta}$-catenin. Immunoblot analysis showed that toxin A increased active phosphorylation of $GSK3{\beta}$. Because the Wnt signaling pathway is essential for gut epithelial cell proliferation and anti-apoptotic processes, our results suggest that toxin A-mediated inhibition of the Wnt signaling pathway may be required for maximal toxin A-induced apoptosis of gut epithelial cells.

Cells Transformed by PLC-Gamma 1 Overexpression are Highly Sensitive to Clostridium difficile Toxin A-Induced Apoptosis and Mitotic Inhibition

  • Nam, Hyo-Jung;Kang, Jin-Ku;Chang, Jong-Soo;Lee, Min-Soo;Nam, Seung-Taek;Jung, Hyun-Woo;Kim, Sung-Kuk;Ha, Eun-Mi;Seok, Heon;Son, Seung-Woo;Park, Young-Joo;Kim, Ho
    • Journal of Microbiology and Biotechnology
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    • v.22 no.1
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    • pp.50-57
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    • 2012
  • Phospholipase C-${\gamma}l$ (PLC-${\gamma}l$) expression is associated with cellular transformation. Notably, PLC-${\gamma}$ is up-regulated in colorectal cancer tissue and breast carcinoma. Because exotoxins released by Clostridium botulinum have been shown to induce apoptosis and promote growth arrest in various cancer cell lines, we examined here the potential of Clostridium difficile toxin A to selectively induce apoptosis in cells transformed by PLC-${\gamma}l$ overexpression. We found that PLC-${\gamma}l$-transformed cells, but not vector-transformed (control) cells, were highly sensitive to C. difficile toxin A-induced apoptosis and mitotic inhibition. Moreover, expression of the proapoptotic Bcl2 family member, Bim, and activation of caspase-3 were significantly up-regulated by toxin A in PLC-${\gamma}l$-transformed cells. Toxin A-induced cell rounding and paxillin dephosphorylation were also significantly higher in PLC-${\gamma}l$-transformed cells than in control cells. These findings suggest that C. difficile toxin A may have potential as an anticancer agent against colorectal cancers and breast carcinomas in which PLC-${\gamma}l$ is highly up-regulated.

Clostridium difficile Toxin A Inhibits Erythropoietin Receptor-Mediated Colonocyte Focal Adhesion Through Inactivation of Janus Kinase-2

  • Nam, Seung Taek;Seok, Heon;Kim, Dae Hong;Nam, Hyo Jung;Kang, Jin Ku;Eom, Jang Hyun;Lee, Min Bum;Kim, Sung Kuk;Park, Mi Jung;Chang, Jong Soo;Ha, Eun-Mi;Shong, Ko Eun;Hwang, Jae Sam;Kim, Ho
    • Journal of Microbiology and Biotechnology
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    • v.22 no.12
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    • pp.1629-1635
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    • 2012
  • Previously, we demonstrated that the erythropoietin receptor (EpoR) is present on fibroblasts, where it regulates focal contact. Here, we assessed whether this action of EpoR is involved in the reduced cell adhesion observed in colonocytes exposed to Clostridium difficile toxin A. EpoR was present and functionally active in cells of the human colonic epithelial cell line HT29 and epithelial cells of human colon tissues. Toxin A significantly decreased activating phosphorylations of EpoR and its downstream signaling molecules JAK-2 (Janus kinase 2) and STAT5 (signal transducer and activator of transcription 5). In vitro kinase assays confirmed that toxin A inhibited JAK 2 kinase activity. Pharmacological inhibition of JAK2 (with AG490) abrogated activating phosphorylations of EpoR and also decreased focal contacts in association with inactivation of paxillin, an essential focal adhesion molecule. In addition, AG490 treatment significantly decreased expression of occludin (a tight junction molecule) and tight junction levels. Taken together, these data suggest that inhibition of JAK2 by toxin A in colonocytes causes inactivation of EpoR, thereby enhancing the inhibition of focal contact formation and loss of tight junctions known to be associated with the enzymatic activity of toxin A.

Tumor Surpressor Gene Therany, and Natural Product with Vectors[Aoenouirus, Aoenn associated virus] in Human Papilloma virus (HPV[Human papilloma virus]유래 바이러스 벡터[Adenovirus, Adeno associated virus]를 이용한 암 억제유전자치료법과 자연산물에서의 암 억제 효과)

  • 천병수;노민석;유종수;김준명
    • KSBB Journal
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    • v.16 no.6
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    • pp.579-591
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    • 2001
  • The cell growth inhibitor effect of cervical cancer cells was investigated by liposome mediated transfection (pRcCMVp53/lipofectin) and by transfection using adenovirus (AdCMVp57). The papilloma virus cancer cell lines we used in this study were HPV16 positive, having inhibiter gene, wild p53 gene, CaSki, SiHa, HPV18 positive HeLa, HeLaS3 and HPV negative C33A, HT3. LacZ gene of E.coli was used as the marker gene for the transfection efficiency. The effect on the inhibition of tumor cell growth was measured by cell count and cell viability though ELISA analysis and MTT assay. The inhibition of tumor cell growth was confirmed by measuring each assay for six days, comparing with the normal control cell growth. The cell growth of cervical cancer calls by transfection was significantly reduced and showed tittle differences among the cell lines. To eliminate the potential problem of Ad(adenovirus) contamination during rAAV production, rAAV can be produced by a triple transfection of vector plasmic, packaging plasmid, and adenovirus helper plasmid. To examine the helper functions of Ad plasmids on the production of rAAV vector, we carried out cotransfection of three plasmids, AAV vector, packaging construct, and Ad helper plasmids. The optimized transfection condition for calcium phosphate method is 25ug of total DNA per 10-cm-diameter plate of 293 cell. We found that rAAV yields peaked at 48hr after Ad infection. The titer of rAAV was measured by the dot blot analysis to measure the number of particles/ml based on the quantification of viral DNA. Recent1y, Kombucha(fungi) was identified as a very potent antileukefic agent. In the present study, effect of natural toxin(plankton) and Kombucha is PSP(GTXI-3, neoSTX), on various MTT assay cervical cancer cell line. Toxin(GTX 1-3, neoSTX) also inhibited the proliferation in primary cervical cancer calls in a dose-dependent toxin concentration. These results showed that toxin was very potent in inhibiting the proliferation of cervical cancer calls in vitro. Toxins and Kombuoha exhibited a dose dependent inhibition of cellular proliferation in cancer cell line.

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Pertussis Toxin Inhibits Colchicine-Induced DNA Synthesis in Human Fibroblast

  • Jang, Won-Hee;Rhee, In-Ja
    • Archives of Pharmacal Research
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    • v.17 no.3
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    • pp.199-203
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    • 1994
  • Several lines evidence indicate that microtubule depolymerization initiates DNA synthesis or enhances the effects of serum or purified growth factors in many types of fibroblasts. Yet little is known about the intracellular events responsible for the mitogenic effect of microtubule disrupting agents. The effects of antitubulin agents on DNA synthesis in sparse and dense cultures in the presence or absence of serum and possible involvement of G-proteins in their mitotic action were examined. In these studies, colchicine by itself appeared to be mitogenic only for confluent quiesecent human lung fibroblasts. In sparse culture, however, colchicine inhibited serum-stimulated DNA synthesis. Colcemid, another antitubulin agent, showed similar effects of growth inhibition and stimulation in sparse and confluent cultures while lumicolhicine, inactive colchicine, did not. The mitogenic effect of two antitubulin agents, colchicine and colcemid, was partially inhibited by pertussis toxin. These data suggest that microtubular integrity is associated with the expression of either negative or positive control on DNA synthesis and mitogenic effect of antitubulin agents may be partially mediated by pertussis toxin-sensitive G protein.

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Inhibition of Bacillus cereus Growth and Toxin Production by Bacillus amyloliquefaciens RD7-7 in Fermented Soybean Products

  • Eom, Jeong Seon;Choi, Hye Sun
    • Journal of Microbiology and Biotechnology
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    • v.26 no.1
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    • pp.44-55
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    • 2016
  • Bacillus cereus is a gram-positive, rod-shaped, spore-forming bacterium that has been isolated from contaminated fermented soybean food products and from the environment. B. cereus produces diarrheal and emetic toxins and has caused many outbreaks of foodborne diseases. In this study, we investigated whether B. amyloliquefaciens RD7-7, isolated from rice doenjang (Korean fermented soybean paste), a traditional Korean fermented soybean food, shows antimicrobial activity against B. cereus and regulates its toxin gene expression. B. amyloliquefaciens RD7-7 exhibited strong antibacterial activity against B. cereus and inhibited the expression of B. cereus toxin-related genes (groEL, nheA, nheC, and entFM). We also found that addition of water extracts of soybean and buckwheat soksungjang (Korean fermented soybean paste made in a short time) fermented with B. amyloliquefaciens RD7-7 significantly reduced the growth and toxin expression of B. cereus. These results indicate that B. amyloliquefaciens RD7-7 could be used to control B. cereus growth and toxin production in the fermented soybean food industry. Our findings also provide a basis for the development of candidate biological control agents against B. cereus to improve the safety of fermented soybean food products.