Biomedical subjects

Jiyun Kim

Publications and source records attributed to Jiyun Kim.

8 recordsLinked to original sources

PubMed2005

Trichostatin A exacerbates atherosclerosis in low density lipoprotein receptor-deficient mice.

OBJECTIVE: Histone acetylation has been shown to be involved in expression of a restricted set of cellular genes including various proinflammatory molecules. We aimed to investigate the relationship between histone acetylation and atherosclerosis. METHODS AND RESULTS: In low-density lipoprotein (LDL) receptor-deficient (Ldlr(-/-)) mice fed an atherogenic diet for 4 or 8 weeks, trichostatin A (TSA), a specific histone deacetylase inhibitor, exacerbated atherosclerosis without alteration on plasma lipid profiles. When we assayed the effects of TSA on expressions of oxidized LDL (oxLDL) receptors on RAW264.7 macrophage, we found that TSA increased CD36 mRNA and protein, as well as cell surface expression of CD36. TSA also increased acetylation at the CD36 promoter region. The uptake of 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine percholate (Dil)-labeled oxLDL was enhanced in RAW264.7 macrophage by TSA. Furthermore, TSA treatment increased CD36 mRNA expression in aorta, and SRA, tumor necrosis factor (TNF)-alpha, and vascular cell adhesion molecule-1 (VCAM-1) were also elevated, whereas IL-6 and IL-1beta expressions were decreased. CONCLUSIONS: Our findings suggest that histone acetylation could play some role in atherogenesis by modulating expressions of oxLDL receptor and some proatherogenic genes. Therefore, our results indicate that increased histone acetylation may affect the progress of atherosclerosis.

Acetylation↗

PubMed2005

Inhibition of cytokine-induced IkappaB kinase activation as a mechanism contributing to the anti-atherogenic activity of tilianin in hyperlipidemic mice.

Tilianin has been shown to down-regulate TNF-alpha induced expression of vascular cell adhesion molecules in endothelial cells. In this study, we examined the anti-atherogenic effects and molecular mechanism of tilianin in vitro and in vivo. Male low-density lipoprotein receptor null mice (Ldlr-/-) fed a high cholesterol diet showed significant increases in the size of atherosclerotic lesions, as well as increased plasma levels of total cholesterol, triglycerides, and the pro-inflammatory cytokines TNF-alpha and IL-1beta, when compared with Ldlr-/- mice fed a normal diet. Mice fed the high cholesterol diet supplemented with tilianin showed significantly reduced lesion sizes and reductions in cytokine levels, without significant changes in serum cholesterol levels. Primary cultured peritoneal macrophages from Ldlr-/- mice showed increased level of TNF-alpha andIL-1beta mRNA in response to treatment with lipopolysaccharide; these increases were inhibited by co-treatment with tilianin. Moreover, tilianin inhibited NF-kappaB activation, as determined by electrophoretic mobility shift and NF-kappaB promoter assays. Upstream of NF-kappaB activation, tilianin inhibited IkappaB kinase activation and the subsequent phosphorylation and degradation of IkappaBalpha protein. These results suggest that tilianin ameliorates atherosclerosis by inhibiting the production of the NF-kappaB-dependent pro-inflammatory cytokines, TNF-alpha and IL-1beta, via the inhibition of IkappaB kinase activity.

Animals↗

PubMed2005

The effects of patient cost sharing on ambulatory utilization in South Korea.

This study focused mainly on the effects of patient cost sharing on the demand for physician service, especially in the low-income people. Patient cost sharing is one of the policies used extensively in the health care financing in Korea, which has been adopted to control the health care cost. It has raised the argument that cost sharing inhibits low-income patients' access to affordable medical care. Data from the National Health and Nutrition Survey conducted 1998 by the Korean Ministry of Health and Welfare was used for this analysis. Multiple regression was done with the dependent variable of the amount of ambulatory utilization and price elasticities are estimated. We obtained significant out-of-pocket price elasticities depending on patient income levels and types of care facilities in the range of -0.21 to -0.07, -0.20 to -0.10, respectively. We found out that low-income patients are more sensitive to cost sharing than high-income patients. Furthermore, we found out that the users of general hospitals are less sensitive to cost sharing than the users of clinics. These results shows that the cost sharing policy in Korea does not efficiently work. Patient cost sharing in Korea induces inequitable medical service utilization and also it does not decrease moral hazard in the sense that the higher cost-sharing sector is less sensitive to cost sharing.

Adult↗

PubMed2004

KR-31378 ameliorates atherosclerosis by blocking monocyte recruitment in hypercholestrolemic mice.

The recruitment of monocytes into the artery wall is a crucial early step in atherogenesis. A novel compound, KR-31378, has been shown to be a neuroprotective agent for ischemia-reperfusion damage in rat brain via its potent antioxidant and antiapoptotic actions. Here, we report the effects of this compound on atherogenesis and possible mechanisms of action. In Ldlr knockout mice fed with a high-fat, high-cholesterol diet, treatment with KR-31378 significantly inhibited fatty streak formation and macrophage accumulation. To address the possibility that KR-31378 may influence the initial stages of atherogenesis, we examined its effect on the adhesion and migration of monocytes to endothelial cells stimulated with tumor necrosis factor-alpha. KR-31378 decreased the adhesion in a dose-dependent manner. The observed decreases in cell adhesion and migration correlated with KR-31378-mediated down-regulation of vascular cell adhesion molecule-1 (VCAM-1) and interleukin (IL)-8. Nuclear factor-kappaB (NF-kappaB) is known to regulate the expression of adhesive and chemotactic molecules including VCAM-1 and IL-8. Indeed, transient transfection experiments, electrophoretic mobility shift assay, and IkappaB degradation assay showed that KR-31378 decreased NF-kappaB activation. These results indicate that KR-31378 potently reduces fatty streak formation by inhibiting NF-kappaB-dependent cellular adhesion and chemotactic molecule expression, which are crucial to monocyte infiltration into the arterial wall during the early stages of atherogenesis.

Animals↗

PubMed2003

BRCA1 associates with human papillomavirus type 18 E2 and stimulates E2-dependent transcription.

BRCA1 is a breast and ovarian cancer-related tumor suppressor and has a role in transcriptional activation. We show here that BRCA1 enhances human papillomavirus type 18 (HPV-18) E2-dependent transcription in vivo. Using biochemical approaches, we discovered that BRCA1 interacts with the carboxyl-terminus of HPV-18 E2 protein in vivo and in vitro. Point mutations in the C-terminus make BRCA1 defective in transcriptional activation in E2-dependent transcription. This finding suggests that the C-terminus of BRCA1 is important for E2-dependent transcription. A chromatin immunoprecipitation assay indicated that BRCA1 is recruited onto the E2-dependent promoter region though E2 tethered to E2 binding sites in vivo. These results implicate that BRCA1 plays a role in E2-dependent transcription.

BRCA1 Protein↗

PubMed2002

Annexin II: a plasminogen-plasminogen activator co-receptor.

Fibrinolysis is a precisely orchestrated process in which fibrin-containing thrombi are solubilized. Several receptors regulate this process by localizing proteolytic activity to the cell surface. One such receptor is annexin II, a calcium and phospholipid-binding protein. Annexin II serves as a profibrinolytic coreceptor for both plasminogen and tissue plasminogen activator on the surface of endothelial cells and facilitates the generation of plasmin. The dysregulation of fibrinolytic assembly on endothelial cells may lead to atherothrombotic disease. In addition to its role in fibrinolysis at the surface of endothelial cells, annexin II may play other potential cellular roles. For example, the overexpression of annexin II on the surface of leukemic cells and cell lines derived from acute promyelocytic leukemia correlates with both the clinical manifestation of bleeding and the in vitro ability of the leukemic cells to generate plasmin. The abundant presence of annexin II on the surface of other cell types including monocytic cell lines and different cancer cells may contribute to their invasive potential through extracellular matrix either by generation of plasmin or, by plasmin-mediated proteolytic activation of other metalloproteinases. This dissolution of extracellular matrix may also cause the release of potent matrix-bound angiogenic factors such as VEGF and FGF. On the other hand, by increasing the pool of plasmin, a precursor to an important anti-angiogenic factor, angiostatin, and by fragmentation of collagen XVIII (a precursor to the anti-angigenic factor, endostatin) by plasmin-activated metalloproteases, annexin II could play a pivotal physiological role in the pro- and anti-angiogenic switch mechanism.

Annexin A2↗

PubMed2001

Functional interaction between p/CAF and human papillomavirus E2 protein.

p300/CREB-binding protein-associated factor (p/CAF), a transcriptional co-activator, interacts with co-activator p300/CBP and acidic transcription factors. p/CAF mediates transcriptional activation by acetylating nucleosomal histones and cellular factors. Previously we reported that CBP binds to human papillomavirus E2 and activates E2-dependent transcription (Lee, D., Lee, B., Kim, J., Kim, D. W., and Choe, J. (2000) J. Biol. Chem. 275, 7045-7051). Here we show that p/CAF binds to the human papillomavirus E2 protein in vivo and in vitro and activates E2-dependent transcription. CBP along with p/CAF synergistically activates E2-dependent transcription. In addition, the histone acetylase activity of p/CAF is required for efficient activation of E2 transcriptional activity. These results suggest that p/CAF is a transcriptional co-activator of the human papillomavirus E2 protein.

Acetyltransferases↗

PubMed2001

Human papillomavirus type 16 E7 binds to E2F1 and activates E2F1-driven transcription in a retinoblastoma protein-independent manner.

The human papillomavirus (HPV) E7 oncoprotein can immortalize primary human cells and induce tumor formation. These properties of E7 depend on its ability to inhibit the activity of retinoblastoma protein (pRB), which in turn affects E2F function. E2F proteins control the expression of genes involved in differentiation, development, cell proliferation, and apoptosis. By using genetic and biochemical approaches, the present study shows that E7 binds to E2F1 in vivo and in vitro and that both proteins co-localize in the nucleus. Importantly, the binding of the high risk group HPV E7 to E2F1 is tighter than the binding of the low risk group HPV E7 to E2F1. Although E7 of the high risk group HPVs activates E2F1-dependent transcription strongly in C33A or 293T cells, E7 of the low risk group HPVs activates transcription only weakly. By using electrophoretic mobility shift assay, we also showed that E7 binds to E2F1-DNA complexes. Furthermore, we show that these activities of E7 are independent of pRB by using E7 and E2F1 mutants that cannot bind to pRB. Taken together, these data suggest that E7 contributes to the deregulation of pRB-dependent E2F1 repression and to the further activation of E2F1 independently of pRB.

Cell Cycle Proteins↗