Biomedical subjects

Sang-Woon Choi

Publications and source records attributed to Sang-Woon Choi.

23 records · Page 2Linked to original sources

PubMed2002

Coagulation parameters and plasma total homocysteine levels in Behcet's disease.

Behcet's disease (BD) is a multisystemic inflammatory disorder of unknown etiology that is sometimes associated with thrombosis in addition to systemic manifestations. However, the mechanism of hypercoagulability is not known. We evaluated the coagulation and fibrinolytic activities and the plasma total homocysteine levels of Korean BD patients in two cross-sectional studies. In the first study regarding coagulation and fibrinolytic activities, the levels of fibrinogen and von Willebrand factor (vWF) antigen were significantly higher in the BD patients than in the healthy controls (387.7+/-24.3 versus 240.6+/-8.8 mg/dl, p<0.001, and 131.9+/-8.8 versus 105.2+/-0.3%, p<0.01, respectively). The level of antithrombin III (AT III) was significantly lower in the BD patients (92.8+/-3.2 versus 106.3+/-2.6%, p<0.005). No differences were observed in the levels of plasminogen, protein C, or protein S activities. Activated protein C (APC) resistance was not observed in any BD patients. In the second study, the plasma total homocysteine levels of patients with a history of thrombosis (11.9+/-3.0 micromol/l) or disease activity (12.5+/-3.8 micromol/l) were found to be significantly higher than those of the controls (9.2+/-2.6 micromol/l, p<0.05, both). The plasma homocysteine concentrations in the thrombosis patients were positively correlated with plasma vWF levels; a relationship which suggests injury of the vascular endothelium (Spearman coefficient=0.857, p<0.01). Therefore, coagulation abnormality did not contribute to thrombotic complications, and higher levels of homocysteine may play a role in the hypercoagulablity of BD patients.

Adult↗

PubMed2002

Folate status and age affect the accumulation of L-isoaspartyl residues in rat liver proteins.

Formation of atypical L-isoaspartyl residues in proteins and peptides is a common, spontaneous and nonenzymatic modification of aspartyl and asparaginyl sites. The enzyme protein-L-isoaspartyl methyltransferase (PIMT) catalyzes the transfer of the methyl group of S-adenosyl-L-methionine (SAM) to these L-isoaspartyl sites, thereby allowing reisomerization and restoration of the original alpha peptide linkage. Because SAM is in part a product of folate metabolism, the present study was undertaken to determine the effects of folate deficiency on the presence of L-isoaspartyl residues in hepatic proteins. Young (weanling) and older (12 mo) Sprague-Dawley rats were fed a folate-sufficient (2 mg folate/kg diet) or folate-deficient (0 mg folate/kg diet) diet for 20 wk. Liver proteins were analyzed for L-isoaspartyl residues. This analysis was based on the PIMT-dependent incorporation of [(3)H]-methyl groups from [(3)H]-SAM and the subsequent (nonenzymatic) sublimation of these methyl groups into a nonaqueous scintillant. The amount of L-isoaspartyl residues in hepatic proteins was higher in younger folate-deficient than in folate-sufficient rats (deficient: 187 +/- 71, sufficient: 64 +/- 43 pmol/mg protein, P < 0.025). This difference, however, was not seen among the older groups of rats who instead exhibited a much larger accumulation of L-isoaspartyl residues in their hepatic proteins (deficient: 528 +/- 151, sufficient: 470 +/- 204 pmol/mg protein, P = 0.568). The importance of these observations is discussed.

Age Factors↗

PubMed2002

In the cystathionine beta-synthase knockout mouse, elevations in total plasma homocysteine increase tissue S-adenosylhomocysteine, but responses of S-adenosylmethionine and DNA methylation are tissue specific.

The cystathionine beta-synthase knockout mouse provides a unique opportunity to study biochemical consequences of a defective cystathionine beta-synthase enzyme. The present study was undertaken to assess the effect of elevated plasma total homocysteine caused by cystathionine beta-synthase deficiency on one-carbon metabolism in 10 homozygous mutant mice and 10 age- and sex-matched wild-type mice. Plasma total homocysteine levels, S-adenosylmethionine and S-adenosylhomocysteine concentrations in liver, kidney and brain were measured by HPLC. Tissue DNA methylation status was measured by in vitro DNA methyl acceptance. Plasma total homocysteine concentration in food-deprived homozygous mutant mice (271.1 +/- 61.5 micro mol/L) was markedly higher than in wild-type mice (7.4 +/- 2.9 micro mol/L) (P < 0.001). In liver only, S-adenosylmethionine concentrations were higher in the homozygous mutant mice (35.6 +/- 5.9 nmol/g) than in wild type mice (19.1 +/- 6.1 nmol/g) (P < 0.001) and tended to be lower in kidney (P = 0.07). In contrast, S-adenosylhomocysteine concentrations were significantly higher in homozygous mutant mice compared with wild-type mice in all tissues studied. Genomic DNA methylation status in homozygous mutant compared with wild-type mice was lower in liver (P = 0.037) and tended to be lower in kidney (P = 0.077) but did not differ in brain (P = 0.46). The results of this study are consistent with the predicted role of cystathionine beta-synthase in the regulation of plasma total homocysteine levels and tissue S-adenosylhomocysteine levels. However, the fact that the absence of the enzyme had differential effects on S-adenosylmethionine concentrations and DNA methylation status in different tissues suggests that regulation of biological methylation is a complex tissue-specific phenomenon.

Animals↗

PubMed2002

Gene-nutrient interactions and DNA methylation.

Many micronutrients and vitamins are critical for DNA synthesis/repair and maintenance of DNA methylation patterns. Folate has been most extensively investigated in this regard because of its unique function as methyl donor for nucleotide synthesis and biological methylation. Cell culture and animal and human studies showed that deficiency of folate induces disruption of DNA as well as alterations in DNA methylation status. Animal models of methyl deficiency demonstrated an even stronger cause-and-effect relationship than did studies using a folate-deficient diet alone. Such observations imply that the adverse effects of inadequate folate status on DNA metabolism are mostly due to the impairment of methyl supply. Recently, an interaction was observed between folate status and a common mutation in the gene encoding for methylenetetrahydrofolate reductase, an essential enzyme in one-carbon metabolism, in determining genomic DNA methylation. This finding suggests that the interaction between a nutritional status with a genetic polymorphism can modulate gene expression through DNA methylation, especially when such polymorphism limits the methyl supply. DNA methylation, both genome-wide and gene-specific, is of particular interest for the study of cancer, aging and other conditions related to cell-cycle regulation and tissue-specific differentiation, because it affects gene expression without permanent alterations in DNA sequence such as mutations or allele deletions. Understanding the patterns of DNA methylation through the interaction with nutrients is fundamental, not only to provide pathophysiological explanations for the development of certain diseases, but also to improve the knowledge of possible prevention strategies by modifying a nutritional status in at-risk populations.

Animals↗

PubMed2002

Folate status: effects on pathways of colorectal carcinogenesis.

Many epidemiologic, animal and human studies suggest that folate status modulates carcinogenesis. Although these observations have been made in a number of tissues, the data are clearly most compelling for the colorectum. The mechanism(s) by which this modulation is mediated remains ill defined. Alterations in either genome-wide or gene-specific DNA methylation and/or alterations in DNA stability, resulting from DNA strand breaks or uracil misincorporation, are leading candidates in this regard. Folate has a central role in biological methylation and nucleotide synthesis, and therefore it is not surprising that folate depletion has been observed to alter DNA methylation and diminish DNA stability. The hypothesis that these two pathways are the means by which folate modulates cancer risk is also supported by the epidemiological observation that a common polymorphism in the methylenetetrahydrofolate reductase (MTHFR; EC 1.5.1.20) gene differentially affects the relative risk of colon cancer depending on folate status, because MTHFR catalyzes the reaction that determines whether cellular folate is diverted into biological methylation or nucleotide synthesis. This phenomenon suggests that it is an imbalance between biological methylation and nucleotide synthesis that is responsible for folate-related carcinogenesis. The control of cell proliferation, which also is related to DNA methylation, is another candidate mechanism by which folate status modulates carcinogenesis. In cell culture studies, folate supplementation has been observed to suppress excessive cell proliferation. Understanding the mechanisms by which folate status modulates carcinogenesis is important for advancing insight into cancer biology and for facilitating those efforts to translate research in folate and carcinogenesis into effective and safe public health initiatives.

Cell Transformation, Neoplastic↗