ABSTRACT
O-linked N-Acetylglucosamine (O-GlcNAc) post-translational modifications originate from the activity of the hexosamine pathway, and are known to affect intracellular signaling processes. As aberrant responses to microenvironmental signals are a feature of chronic lymphocytic leukemia (CLL), O-GlcNAcylated protein levels were measured in primary CLL cells. In contrast to normal circulating and tonsillar B cells, CLL cells expressed high levels of O-GlcNAcylated proteins, including p53, c-myc and Akt. O-GlcNAcylation in CLL cells increased following activation with cytokines and through toll-like receptors (TLRs), or after loading with hexosamine pathway substrates. However, high baseline O-GlcNAc levels were associated with impaired signaling responses to TLR agonists, chemotherapeutic agents, B cell receptor crosslinking and mitogens. Indolent and aggressive clinical behavior of CLL cells were found to correlate with higher and lower O-GlcNAc levels, respectively. These findings suggest that intracellular O-GlcNAcylation is associated with the pathogenesis of CLL, which could potentially have therapeutic implications.
Subject(s)
Acetylglucosamine/metabolism , Leukemia, Lymphocytic, Chronic, B-Cell/metabolism , Acylation , Adult , Aged , Aged, 80 and over , Base Sequence , Cytokines/metabolism , DNA Primers , Female , Humans , Immunophenotyping , Leukemia, Lymphocytic, Chronic, B-Cell/pathology , Male , Middle Aged , Polymerase Chain Reaction , Toll-Like Receptors/metabolism , Tumor Cells, CulturedABSTRACT
We present high resolution 133Cs-13C double resonance NMR data and 13C-13C NMR correlation spectra of 13C enriched samples of the polymeric phase of CsC60. These data lead to a partial assignment of the lines in the 13C NMR spectrum of CsC60 to the carbon positions on the C60 molecule. A plausible completion of the assignment can be made on the basis of an ab initio calculation. The data support the view that the conduction electron density is concentrated at the C60 "equator," away from the interfullerene bonds.
ABSTRACT
The hydrothermal synthesis, single-crystal structure analysis, spectroscopic studies, and thermal stability of the compounds Ca(2)(In(1)(-)(x)()Fe(x)())(PO(4))(HPO(4))(2).H(2)O (0
ABSTRACT
Chloramphenicol (CAP, RNHCOCHCl2) has previously been shown to be dechlorinated to CAP aldehyde (RNHCOCHO) and CAP oxamic acid (RNHCOCO2H) by rat liver cytosol. In the present study we have further characterized these reactions and have found that several homogeneous rat liver GSH transferases, particularly transferases A, metabolize CAP to CAP aldehyde by an apparent hydrolytic dechlorination mechanism. The aldehyde is further metabolized to CAP oxamic acid by an aldehyde oxidizing enzyme(s) which does not require GSH, but can utilize either NAD+ or NADP+. Thiamphenicol, the p-methylsulfonylphenyl derivative of CAP, also appears to be metabolized through these pathways, but to a lesser extent than is CAP.
