19 research outputs found
13 C-, 15 N- and 31 P-NMR studies of oxidized and reduced low molecular mass thioredoxin reductase and some mutant proteins
Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65853/1/j.1432-1033.2004.04043.x.pd
Competitive cobalt for zinc substitution in mammalian methionine sulfoxide reductase B1 overexpressed in E. coli: structural and functional insight
Role of α5β1 Integrin Up-regulation in Radiation-Induced Invasion by Human Pancreatic Cancer Cells1
Radiotherapy is used in the management of pancreatic cancer because of its high propensity for locoregional relapse: one third of patients succumb to localized disease. Thus, strategies to improve the efficacy of radiotherapy in pancreatic cancer are important to pursue. We used naturally serum-free, selectively permeable basement membranes and confocal microscopy of fluorescent antibody-stained human Panc-1, MiaPaCa-2, and BxPC-3 pancreatic cancer cell lines to investigate the effects of ionizing radiation on α5β1 integrin fibronectin receptor expression and on α5β1-mediated invasion. We report that radiation rapidly induces pancreatic cancer cell invasion, and that radiation-induced invasion is caused by up-regulation of α5β1 integrin fibronectin receptors by transcriptional and/or postendocytic recycling mechanisms. We also report that radiation causes α5β1 up-regulation in Panc-1, MiaPaCa-2, and BxPC-3 tumor xenografts and that upregulated α5β1 colocalizes with upregulated early or late endosomes in Panc-1 or BxPC-3 tumors, respectively, although it may colocalize significantly with both endosome types in MiaPaCa-2 tumors. Our results suggest that systemic inhibition of α5β1-mediated invasion might be an effective way to reduce radiation-induced pancreatic cancer cell invasion, thereby improving the efficacy of radiotherapy
The Relationship of the Redox Potentials of Thioredoxin and Thioredoxin Reductase from Drosophila melanogaster
Analysis of the kinetic and redox properties of NADH peroxidase C42S and C42A mutants lacking the cysteine-sulfenic acid redox center
Vpliv učenja in obsega žoge na spremembo hitrosti rokometnega strela
Thioredoxin, involved in numerous
redox pathways, is maintained
in the dithiol state by the nicotinamide adenine dinucleotide phosphate-dependent
flavoprotein thioredoxin reductase (TrxR). Here, TrxR from <i>Lactococcus lactis</i> is compared with the well-characterized
TrxR from <i>Escherichia coli</i>. The two enzymes belong
to the same class of low-molecular weight thioredoxin reductases and
display similar <i>k</i><sub>cat</sub> values (∼25
s<sup>–1</sup>) with their cognate thioredoxin. Remarkably,
however, the <i>L. lactis</i> enzyme is inactivated by visible
light and furthermore reduces molecular oxygen 10 times faster than <i>E. coli</i> TrxR. The rate of light inactivation under standardized
conditions (λ<sub>max</sub> = 460 nm and 4 °C) was reduced
at lowered oxygen concentrations and in the presence of iodide. Inactivation
was accompanied by a distinct spectral shift of the flavin adenine
dinucleotide (FAD) that remained firmly bound. High-resolution mass
spectrometric analysis of heat-extracted FAD from light-damaged TrxR
revealed a mass increment of 13.979 Da, relative to that of unmodified
FAD, corresponding to the addition of one oxygen atom and the loss
of two hydrogen atoms. Tandem mass spectrometry confined the increase
in mass of the isoalloxazine ring, and the extracted modified cofactor
reacted with dinitrophenyl hydrazine, indicating the presence of an
aldehyde. We hypothesize that a methyl group of FAD is oxidized to
a formyl group. The significance of this not previously reported oxidation
and the exceptionally high rate of oxygen reduction are discussed
in relation to other flavin modifications and the possible occurrence
of enzymes with similar properties