75 research outputs found
Metabolic Fingerprinting in Toxicological Assessment Using FT-ICR MS
Detection of the toxicity of a candidate compound at an early stage of drug
development is an emerging area of interest. It is difficult to determine all of
the effects of metabolism of a compound using traditional approaches such as
histopathology and serum biochemistry. The goal of a metabolomics approach is to
determine all metabolites in a living system, with the potential to detect and
identify biomarkers involved in toxicity onset. Here, we summarize the metabolic
fingerprints for detection and identification of metabolic changes and
biomarkers related to drug-induced toxicity using Fourier transform ion
cyclotron resonance mass spectrometry (FT-ICR MS)
Slit3 regulates cell motility through Rac/Cdc42 activation in lipopolysaccharide-stimulated macrophages
AbstractThree slit genes, slit1 to slit3, have been cloned to date. Slit1 and slit2 act as chemorepellent factors for axon guidance. Slit3 is involved in the formation of the diaphragm and kidney during embryogenesis. However, its molecular function remains unclear. We found that slit3 expression was induced by lipopolysaccharide (LPS)-stimulation in macrophages and that it was localized in the mitochondria and along the plasma membrane. Silencing of slit3 expression by RNA interference reduced cell motility and Rac/Cdc42 activation. These results suggest that slit3 functions as an intracellular signaling molecule for cell motility as part of the LPS-induced signaling cascade
Characterization of a novel monoclonal antibody that senses nitric oxide-dependent activation of soluble guanylate cyclase
AbstractTwo monoclonal antibodies (mAbs) against bovine lung soluble guanylate cyclase (sGC) were prepared and characterized. mAb 3221 recognized both the α- and β-subunits of sGC and had greater binding affinity to the enzyme in the presence of NO. mAb 28131 recognized only the β-subunit and its affinity did not change with NO. Neither mAb cross-reacted with particulate GC. Cultured Purkinje cells from rats were treated with S-nitroso-N-acetylpenicillamine, an NO donor, and examined by immunocytochemical methods. The immunoreactivity associated with mAb 3221 increased with the cGMP content in a crude extract of cerebellum and the NO2 generated in the culture medium increased
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