Search results for "toxin"

Inefficient Termination of Antigen Responses in NF-ATp-Deficient Mice

1998

In order to elucidate the role of NF-ATp, one of the most prominent members of family of NF-AT transcription factors in peripheral T lymphocytes, in T cell activation and differentiation we created NF-ATp-deficient mice by gene targeting. Such NF-ATp-/- mice are born and appear to develop a normal immune system. Apart from clear-cut defects in the synthesis of mRNAs for Th2-type lymphokines, such as IL-4, IL-5, IL-10 and IL-13, in primary and secondary stimulations of spleen cells in vitro, of a distinct impaired deletion of V beta 11+/CD4+ T lymphocytes from these mice was detected after superantigen injection. Moreover, NF-ATp-/- mice older than 6 weeks show an 2-5 fold increase in number…

A Superantigen as Virulence Factor in an Acute Bacterial Infection

1994

This study addresses the role of a bacterial superantigen as a potential virulence factor during an acute systemic infection. BALB/c mice were intravenously infected with a recombinant Staphylococcus aureus strain capable of producing plasmid-encoded staphylococcal enterotoxin B (SEB) or with the SEB plasmid-deficient parental strain. Infection with SEB-producing bacteria resulted in an initial expansion and subsequent decrease of circulating V beta 8+ T lymphocytes. This numeric decrease was accompanied by a SEB-specific state of hyporesponsiveness of splenic T cells. In parallel with SEB-triggered unresponsiveness of a large proportion of T lymphocytes, a weakening of the overall T cell r…

Focal adhesions are hotspots for keratin filament precursor formation

2006

Recent studies showed that keratin filament (KF) formation originates primarily from sites close to the actin-rich cell cortex. To further characterize these sites, we performed multicolor fluorescence imaging of living cells and found drastically increased KF assembly in regions of elevated actin turnover, i.e., in lamellipodia. Abundant KF precursors (KFPs) appeared within these areas at the distal tips of actin stress fibers, moving alongside the stress fibers until their integration into the peripheral KF network. The earliest KFPs were detected next to actin-anchoring focal adhesions (FAs) and were only seen after the establishment of FAs in emerging lamellipodia. Tight spatiotemporal …

Towards the Development of Antitumor Vaccines: A Synthetic Conjugate of a Tumor-Associated MUC1 Glycopeptide Antigen and a Tetanus Toxin Epitope.

2000

Proliferation of cytotoxic T-cells, a prerequisite for the development of antitumor vaccines, was induced by 1, but not by its partial structures A and B. The conjugate 1 containing a tumor-associated Sialyl-TN -MUC-1 glycopeptide antigen A and a T-cell epitope B of tetanus toxin was synthesized by fragment condensation on a solid phase.

Botulinum toxin injections into the detrusor

2011

Glucosylation of Rho proteins by Clostridium difficile toxin B.

1995

TOXIN A and B, the major virulence factors of Clostridium difficile, are the causative agents of antibiotic-associated pseudomembran-ous colitis. In cultured cell lines their potent cytotoxicity results from their ability to induce disaggregation of the microfilament cytoskeleton1,2. Toxin B acts on the low-molecular-mass GTPase Rho A3,4, which is involved in the regulation of the actin cytoskeleton. We report here that toxin B catalyses the incorporation of up to one mole of glucose per mole of RhoA at the amino acid thre-onine at position 37. The modification was identified and localized by tandem electrospray mass spectrometry. UDP-glucose selectively serves as cosubstrate for the monogl…

Ras, Rap, and Rac Small GTP-binding Proteins Are Targets for Clostridium sordellii Lethal Toxin Glucosylation

1996

Lethal toxin (LT) from Clostridium sordellii is one of the high molecular mass clostridial cytotoxins. On cultured cells, it causes a rounding of cell bodies and a disruption of actin stress fibers. We demonstrate that LT is a glucosyltransferase that uses UDP-Glc as a cofactor to covalently modify 21-kDa proteins both in vitro and in vivo. LT glucosylates Ras, Rap, and Rac. In Ras, threonine at position 35 was identified as the target amino acid glucosylated by LT. Other related members of the Ras GTPase superfamily, including RhoA, Cdc42, and Rab6, were not modified by LT. Incubation of serum-starved Swiss 3T3 cells with LT prevents the epidermal growth factor-induced phosphorylation of m…

Oxidative DNA damage and disturbance of antioxidant capacity by alternariol in Caco-2 cells

2015

Oxidative stress occurs as a consequence of an imbalance between the prooxidant/antioxidant systems, causing an increase of intracellular generation of reactive oxygen species. Alternariol (AOH), a mycotoxin produced by Alternaria sp. can alter the action of glutathione (GSH) and the enzymes involved in the redox system, causing damage to cellular macromolecules such as DNA. The aims of this work were to determine the induction of oxidative stress by the antioxidant defenses imbalance in relation to glutathione (GSH), glutathione reductase (GR), glutathione transferase (GST), glutathione peroxidase (GPx) levels and DNA damage in Caco-2 cells derived from adenocarcinoma human colon. Oxidativ…

The actin-based motility of intracellularListeria monocytogenesis not controlled by small GTP-binding proteins of the Rho- and Ras-subfamilies

1999

In this study, we analyzed whether the actin-based motility of intracellular Listeria monocytogenes is controlled by the small GTP-binding proteins of the Rho- and Ras-subfamilies. These signalling proteins are key regulatory elements in the control of actin dynamics and their activity is essential for the maintenance of most cellular microfilament structures. We used the Clostridium difficile toxins TcdB-10463 and TcdB-1470 to specifically inactivate these GTP-binding proteins. Treatment of eukaryotic cells with either of these toxins led to a dramatic breakdown of the normal actin cytoskeleton, but did not abrogate the invasion of epithelial cells by L. monocytogenes and had no effect on …

Interactive effects of zearalenone and its metabolites on cytotoxicity and metabolization in ovarian CHO-K1 cells.

2014

Zearalenone (ZEA) is a non-steroidal estrogen mycotoxin with high binding affinity to estrogen receptors. ZEA is rapidly absorbed and metabolized in vivo to α-zearalenol (α-ZOL) and β-zearalenol (β-ZOL). So, mixtures of them may be present in biological systems and suppose a hazard to animals and human health. The aims of this study were to determine the cytotoxic effects of ZEA and its metabolites, alone and in combination in ovarian (CHO-K1) cells during 24, 48 and 72h by the MTT assay; and to investigate the metabolism of the CHO-K1 cells on ZEA, and its conversion into α-ZOL and β-ZOL by CHO-K1 cell after 24 and 48h of exposure. The IC50 value obtained for individual mycotoxins range fr…