|Quantitative proteomic analysis of oligodendrogliomas with and without 1p/19q deletion. |
Robert C Rostomily,Donald E Born,Richard P Beyer,Jinghua Jin,Ellsworth C Alvord,Andrei M Mikheev,Russell T Matthews,Catherine Pan,Leila Khorasani,Josh A Sonnen,Thomas J Montine,Min Shi,Jing Zhang
Journal of proteome research
Approximately 50-80% of oligodendrogliomas demonstrate a combined loss of chromosome 1p and 19q. Chromosome 1p/19q deletion, appearing early in tumorigenesis, is associated with improved clinical outcomes, including response to chemotherapy and radiation. Although many hypotheses have been proposed, the molecular mechanisms underlying improved clinical outcomes with 1p/19q deletion in oligodendrogliomas have not been characterized fully. To investigate the molecular differences between oligodendrogliomas, we employed an unbiased proteomic approach using microcapillary liquid chromatography mass spectrometry, along with a quantitative technique called isotope-coded affinity tags, on patient samples of grade II oligodendrogliomas. Following conventional biochemical separation of pooled tumor tissue from five samples of undeleted and 1p/19q deleted grade II oligodendrogliomas into nuclei-, mitochondria-, and cytosol-enriched fractions, relative changes in protein abundance were quantified. Among the 442 total proteins identified, 163 nonredundant proteins displayed significant changes in relative abundance in at least one of the three fractions between oligodendroglioma with and without 1p/19q deletion. Bioinformatic analyses of differentially regulated proteins supported the potential importance of metabolism and invasion/migration to the codeleted phenotype. A subset of altered proteins, including the pro-invasive extracellular matrix protein BCAN, was further validated by Western blotting as candidate markers for the more aggressive undeleted phenotype. These studies demonstrate the utility of proteomic analysis to identify candidate biological motifs and molecular mechanisms that drive differential malignancy related to 1p19q phenotypes. Future analysis of larger patient samples are warranted to further refine biomarker panels to predict biological behavior and assist in the identification of deleted gene products that define the 1p/19q phenotype.Full Text Article
|The function, composition, and particle size of high-density lipoprotein were severely impaired in an oliguric phase of hemorrhagic fever with renal syndrome patients. |
Kyung-Hyun Cho, Sun-Hyun Park, Jeong Euy Park, Young Ok Kim, Inho Choi, Jong-Joo Kim, Jae-Ryong Kim
BACKGROUND: Patients suffering from hemorrhagic fever with renal syndrome (HFRS) often showed strikingly reduced high-density lipoprotein (HDL)-cholesterol levels during the oliguric phase, indicating severe alterations in lipoprotein metabolism. OBJECTIVE: To compare changes in the functions and composition of HDL, lipoprotein metabolism parameters were analyzed in the sera of HFRS patients in the oliguric phase and after recovery. METHODS: The serum cholesterol, triglyceride (TG), and lipoprotein/apolipoprotein profiles of HFRS patients in the oliguric and recovery phases were compared with those of normal reference sera. The activities of HDL-associated enzymes, lecithin:cholesterol acyltransferase (LCAT), and paraoxonase (PON) were also assessed. RESULTS: In the oliguric phase, serum cholesterol was substantially decreased and serum TG was increased. As observed by electron microscopy, the sizes of the HDL particles from the HFRS patients were smaller than those seen in the reference sera, with more heterogeneous distribution. Serum amyloid A (SAA) and apolipoprotein (apo) C-III were overexpressed in the oliguric phase, particularly in the HDL fraction. However, in immunodetection, the levels of apoA-I in the HDL(2) and HDL(3) of the HFRS patients were lower than those of the reference HDL. Serum LCAT and PON activities were reduced significantly in the oliguric phase, which is associated with a reduction in HDL-cholesterol levels and HDL particle size. CONCLUSION: Overexpression of both apoC-III and apoSAA in HDL and attenuated serum LCAT and PON activity were observed during the oliguric phase in HFRS patients. These results demonstrate that structural, functional, and compositional changes of HDL occurred to a substantial degree in the oliguric phase.
|Enhanced functional and structural properties of high-density lipoproteins from runners and wrestlers compared to throwers and lifters. |
Lee H, Park JE, Choi I, Cho KH.
Plasma high-density lipoprotein cholesterol (HDL-C) levels are inversely correlated with the risk of cardiovascular disease, and are known to increase with repetitive exercise. In the current study, HDL fractions from athletes' sera were isolated and compared as a function of the type of sport (runners [n = 10], throwers [n = 10], wrestlers [n = 10], and weight lifters [n = 8]), and as an age- and gender-matched reference group (n = 14). Among athletes, HDL from runners had the strongest antioxidant activity. Immunodetection showed that runners and wrestlers had the highest levels of apoA-I and lowest levels of apoA-II in their HDL. Electron microscopy also revealed that HDL(2) of runners and wrestlers were the largest in size. In conclusion, although all athlete groups had significantly better serum lipid/lipoprotein profiles than the reference group, runners and wrestlers had the most desirable lipoprotein function and structure, including antioxidant activity, HDL-associated enzyme activities and increased particle size. [BMB reports 2009; 42(9): 605-610].