Biosynthesis and Processing by Phorbol Ester of the Cell Surface-Associated Precursor Form of Heparin-Binding EGF-like Growth Factor
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Diphtheria Toxin
Diphtheria Toxin
Corynebacterium diphtheriae
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The action of ricin toxin was stimulated by addition of methylamine or some other amines, as shown by measuring the inhibition of protein synthesis of cultured cells by the toxin. Under the same conditions, however, the action of diphtheria toxin was completely inhibited by the amines. In a cell-free protein-synthesizing system, methylamine had no effect on the action of the A chain of ricin toxin and fragment A of diphtheria toxin. Studies on the interactions of 125I-labeled toxins with cells revealed that methylamine did not alter toxin-receptor bindings, but affected the entry of the toxins into the cells. Studies were also made on the effects of methylamine on the actions of two hybrid toxins, formed from a subunit of Wistaria floribunda lectin and fragment A of diphtheria toxin and the A chain of ricin toxin, respectively. Results suggested that the processes of entry of ricin toxin and diphtheria toxin, or at least parts of these processes, are different.
Diphtheria Toxin
Ricin
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Platelet-derived growth factor
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This study describes the expression, purification, and characterization of a recombinant fusion toxin, DAB(389)TTC, composed of the catalytic and membrane translocation domains of diphtheria toxin (DAB(389)) linked to the receptor binding fragment of tetanus toxin (C-fragment). As determined by its ability to inhibit cellular protein synthesis in primary neuron cultures, DAB(389)TTC was approximately 1,000-fold more cytotoxic than native diphtheria toxin or the previously described fusion toxin, DAB(389)MSH. The cytotoxic effect of DAB(389)TTC on cultured cells was specific toward neuronal-type cells and was blocked by coincubation of the chimeric toxin with tetanus antitoxin. The toxicity of DAB(389)TTC, like that of diphtheria toxin, was dependent on passage through an acidic compartment and ADP-ribosyltransferase activity of the DAB(389) catalytic fragment. These results suggest that a catalytically inactive form of DAB(389)TTC may be useful as a nonviral vehicle to deliver exogenous proteins to the cytosolic compartment of neurons.
Diphtheria Toxin
Corynebacterium diphtheriae
Anthrax toxin
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Heparin-Binding Epidermal Growth Factor (HB-EGF) is growth factor member of EGF family that stimulate differentiation and growth. HB-EGF was initially identified as a secreted product of human macrophage-like cells, it is sinthetized as a transmembrana protein; proHB-EGF; that is shed by specific metalloproteases, releasing soluble growth factor(sHB-EGF). It exerts biological activity trough activation of the EGFR. sHB-EGF is implicated in diverse biological processes: angiogenesis, shin wound, blastocysts implantation, atherosclerosis, tumor formation moreover it acts as the Diphtheria Toxin (DT) receptor. HB-EGF It's an important molecule because could be a novel targeting for cancer and atherosclerosis therapy.
Diphtheria Toxin
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Diphtheria toxin-binding glycoproteins of high molecular weight (greater than 100,000) were identified on the surface of lymph node and thymus cells from hamsters, a diphtheria toxin-sensitive species. These diphtheria toxin-binding glycoproteins also interacted with CRM197 protein, which possesses toxin-blocking activity, but not with diphtheria toxoid, fragment A of diphtheria toxin, or cholera toxin, all of which lack toxin-blocking activity. These observations are consistent with the hypothesis that the detected diphtheria toxin-binding glycoproteins are involved in intoxication of cells by this toxin and possibly serve as the plasma membrane receptors for diphtheria toxin.
Diphtheria Toxin
ADP-ribosylation
Cholera toxin
Corynebacterium diphtheriae
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Differences in sensitivity to diphtheria toxin of several toxin-sensitive and toxin-resistant human and non-human cell lines were compared. A method is described whereby it is possible to compare the sensitivity of one cell line with another and obtain meaningful quantitative results. Based on the concentration of toxin required to produce 50% inhibition of protein synthesis after 24 h of exposure the ID50 (24) value toxin-resistant cells were found to be 105 to 106 times more resistant to toxin than toxin-sensitive cells. There was little variation in the ID50 (24) values for cells in each of the two groups. The toxin-resistant cells used in this study, naturally resistant as well as selected variants, possess elongation factor 2 which is susceptible to inactivation by toxin. It is suggested that they are capable of activation of toxin but either cannot bind toxin or are unable to transport toxin across the plasma membrane. Protein synthesis is inhibited when these resistant cells are exposed to high concentrations of toxin. Under these conditions it is likely that enough toxin is able to bypass the block in toxin-specific entry and reach the cytosol by a second, less efficient, nonspecific mechanism to catalyze the inactivation of elongation factor 2 and inhibit protein synthesis.
Diphtheria Toxin
ADP-ribosylation
Elongation factor
Anthrax toxin
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치주인대섬유모세포들은 완전탈구 된 치아의 성공적인 재식을 위한 중요한 요소이다. 따라서, 외상으로 인해 완전탈구된 치아의 보존을 위한 보관액을 선택하는 것이 중요하다. 성장인자들과 호르몬들은 치주인대섬유모세포들의 생존을 위한 치료적 제제로 고려되고 있다. Epidermal growth factor(EGF)는 다른 조직에서 재생과 상처 치유 과정의 중요한 역할인자로 대두되고 있다. 따라서, 완전탈구 된 치아를 위한 치료적 적용을 위해 EGF의 세포 증식에 미치는 영향을 평가하였다. 또한 EGF와 tri-iodothyronine(T3)의 혼합액, EGF와 Heparin-binding epidermal growth factor-like growth factor(HB-EGF)의 혼합액이 세포 증식에 미치는 상승 효과를 평가하였다. 치주인대섬유모세포의 세포증식은 EGF 농도가 증가함에 따라 증가하였고, 10 ng/ml 농도에서 최대 세포증식을 보였다. EGF는 상처치유분석에서 상처 치유촉진과 이동성을 보여주었다. EGF에 T3와 HB-EGF를 첨가한 혼합액에서 배양한 세포는 EGF만 처리한 경우보다 세포 증식이 상승되었다. EGF와 T3 혼합액의 상승효과 기전을 유추하기 위해서 RT-PCR로 EGF 수용기의 발현을 확인하였고, T3가 EGF 수용기 발현을 증가시켰음을 확인하였다. 따라서 EGF와, EGF와 T3, EGF와 HB-EGF의 혼합액은 완전탈구된 치아의 치료에 있어 유용한 선택이 될 것이다. 【Viable cells of periodontal ligament would be an important factor for the successful replantation of an avulsed tooth. Therefore, it is critical to choose the storage medium for the preservation of traumatically avulsed teeth. Growth factors and hormones could be considered for the therapeutic application of the maintenance of viable periodontal ligament fibroblasts (PDLFs). Epidermal growth factor (EGF) has been suggested as an important player for the regeneration and wound healing process on other tissues. Therefore, EGF was evaluated for the therapeutic application on avulsed teeth. In addition, the synergic effect of EGF with tri-iodothyronine (T3) and heparin-binding epidermal growth factor-like growth factor (HB-EGF). The cell proliferation of PDLFs was determined by MTT assay and increased dose-dependently up to 10 ng/ml in the presence of EGF. Maximum cellular growth was shown at the concentration of 10 ng/ml EGF. Also, EGF promoted the wound healing of PDLFs examined by in vitro wound healing assay. Combined effects of EGF with T3 or HB-EGF on the proliferation of PDLFs were also studied. Interestingly, EGF showed the synergic effect on the proliferation of PDLFs with T3 and HB-EGF. To find out the mechanism of the synergic effect of EGF and T3, the effect of T3 on the expression of endogenous EGF receptor was determined by RT-PCR. The result was that T3 enhanced the expression of EGF receptor in PDLFs. It suggested that EGF might be a good choice for a therapeutic application, which can be used as combination with T3 and HB-EGF.】
Periodontal fiber
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Human ectocervical epithelial cells are a primary target for infection by oncogenic papillomaviruses, which are strongly implicated as causative agents in the genesis of cervical cancer. Growth factors have been implicated as agents that stimulate proliferation and enhance the possibility of malignant transformation. In the present study we utilize several human papillomavirus (HPV) type 16-immortalized ectocervical epithelial cell lines to investigate the effects of epidermal growth factor (EGF) and insulin-like growth factor I (IGF-I) on cell proliferation and the production of IGF binding proteins (IGFBPs). ECE16-1 cells, an HPV16-immortalized/nontumorigenic cell line, maintained in defined medium, produce and release high levels of IGFBP-3 (38/42 kDa) as well as smaller amounts of a 24-kDa IGFBP. Supplementation of defined medium with EGF causes a dose-dependent increase in cell growth and a concomitant decrease in the levels of IGFBP-3 released into the culture medium. EGF suppression of IGFBP-3 is maintained even when EGF-stimulated cell growth is suppressed 67% due to the simultaneous presence of 3 ng/ml of TGF beta 1, indicating that EGF suppression of IGFBP-3 levels is independent of EGF effects on cell growth. EGF suppression of IGFBP-3 production is correlated with a reduction in IGFBP-3 mRNA level. In the presence of EGF, the growth response of the cells to ng amounts of IGF-I is significantly enhanced. Moreover, the simultaneous presence of both EGF and IGF-I reduces the level of IGFBP-3 more efficiently than EGF alone. We also observe that the IGFBP-3 level is decreased and the 24-kDa IGFBP level is increased in HPV16-positive tumorigenic versus nontumorigenic cell lines. This is the first report of EGF acting as a positive regulator of IGF-I action via the IGFBPs. On the basis of these findings, we propose that EGF stimulates ECE16-1 cell growth via a dual-action mechanism by (a) stimulating growth directly via the EGF mitogenic pathway and (b) stimulating growth indirectly by reducing the levels of inhibitory IGFBPs and thereby potentiating the effects of IGF-I. In addition, the observation that more highly transformed cell types produce lower levels of IGFBP-3 and higher levels of 24-kDa IGFBP suggests that tumor cells in more advanced cervical cancers may have an altered response to IGF-I.
Immortalised cell line
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Summary Whereas diphtheria and the mechanism of action of diphtheria toxin, the bacterial molecule that induces the disease, have been studied and understood for some time, the receptor that allows animal cells to bind the toxin escaped identification until recently. The receptor was identified by its ability to confer toxin‐sensitivity to mouse cells, which are normally toxin‐resistant. Although mice are also naturally resistant, we now demonstrate that transgenic mice expressing the diphtheria toxin receptor are as sensitive to the toxin as are humans and other toxin‐sensitive animals. These transgenic mice provide a suitable model for studying modern antidotes for diphtheria.
Diphtheria Toxin
Corynebacterium diphtheriae
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