EC Number   |
Application |
Reference |
|---|
   3.4.24.83 | medicine |
mice immunized with chloroplast-derived anthrax protective antigen survive anthrax lethal toxin challenge |
668928 |
| 3.4.24.83 | medicine |
neuronal nitric oxide synthase deficiency in mice causes strikingly increased sensitivity to anthrax lethal toxin, while deficiencies in NOS enzymes iNOS and eNOS have no effect on anthrax lethal toxin-mediated mortality. The increased sensitivity of nNOS2/2 mice is independent of macrophage sensitivity to toxin, or cytokine responses, and can be replicated in nNOS-sufficient wild-type mice through pharmacological inhibition of the enzyme with 7-nitroindazole. Anthrax lethal toxin induces architectural changes in heart morphology of nNOS2/2 mice, with rapid appearance of novel inter-fiber spaces but no associated apoptosis of cardiomyocytes. Anthrax lethal toxin-treated wild-type mice have no histopathology observed at the light microscopy level. Electron microscopic analyses reveal striking pathological changes in the hearts of both nNOS2/2 and wild-type mice, varying only in severity and timing. Endothelial andcapillary necrosis and degeneration, inter-myocyte edema, myofilament and mitochondrial degeneration, and altered sarcoplasmic reticulum cisternae are observed in both anthrax lethal toxin-treated wild-type and nNOS2/2 mice. Biomarkers of cardiac injury, myoglobin, cardiac troponin-I, and heart fatty acid binding protein, are elevated in anthrax lethal toxin-treated mice very rapidly and reach concentrations rarely reported in mice. The potent nitric oxide scavenger, 2-(4-carboxyphenyl)-4,5-dihydro-4,4,5,5-tetramethyl-1H-imidazolyl-1-oxy-3-oxide, i.e. carboxy-PTIO, shows some protective effect against anthrax lethal toxin |
713382 |
| 3.4.24.83 | medicine |
seven of eleven acute myeloid leukemia cell lines show cytotoxic responses to anthrax lethal toxin LeTx. Cytotoxicity is mimicked by the specific mitogen-activated protein/extracellular signal-regulated kinase kinase 1/2 inhibitor U0126, indicating involvement of the ERK1/2 branch of the MAPK pathway. The four LeTx-resistant cell lines are sensitive to the phosphatidylinositol 3-kinase inhibitor LY294002. with a lack of additive/synergistic effects when both pathways are inhibited. Phospho-ERK1/2 is only present in LeTx-sensitive cells. LeTx-induced cell death is caspase-independent and nonapoptotic |
735320 |
| 3.4.24.83 | medicine |
sublethal doses of Bacillus anthracis lethal toxin inhibit inflammation with lipopolysaccharide and Escherichia coli challenge but have opposite effects on survival |
669743 |
| 3.4.24.83 | medicine |
the antitumor toxin has potential for use in cancer therapy |
680918 |
| 3.4.24.83 | medicine |
the use of drugs capable of inhibiting Rho GTPase activity, such as statins, may provide a means to attenuate intoxication during Bacillus anthracis infection |
698254 |
| 3.4.24.83 | molecular biology |
anthrax lethal toxin treatment of neutrophils disrupts signaling to downstream MAPK targets in response to TLR stimulation. Following anthrax lethal toxin treatment, ERK family and p38 phosphorylation are nearly completely blocked, but signaling to JNK family members persists in vitro and ex vivo. In contrast to previous reports involving human neutrophils, anthrax lethal toxin treatment of murine neutrophils increases their production of superoxide in response to PMA or TLR stimulation in vitro or ex vivo. Although this enhanced superoxide production correlates with effects due to the lethal toxin-induced blockade of ERK signaling, it requires JNK signaling that remains largely intact despite the activity of anthrax lethal toxin |
699322 |
| 3.4.24.83 | molecular biology |
Bacillus anthracis represses the immune response, in part by altering chromatin accessibility of IL-8 promoter to NFkappaB in epithelial cells. This epigenetic reprogramming, in addition to previously reported effects of lethal toxin, represents an efficient strategy used by Bacillus anthracis for invading the host |
700915 |
| 3.4.24.83 | molecular biology |
celastrol is identified as an inhibitor of lethal toxin-mediated macrophage lysis and suggests an inhibitory mechanism involving inhibition of the proteasome pathway |
700878 |
| 3.4.24.83 | molecular biology |
it is shown that treatment of RAW 264.7 murine macrophage cells with anthrax lethaltoxin induces autophagy suggesting a protective role as autophagy inhibition using 3-methyladenine results in an accelerated cell death |
696028 |
