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Abstract
목차
Ⅰ. Introduction 10
Ⅱ. Review of Literature 13
Ⅲ. Materials and Methods 24
LDL preparation and modification 24
Characterization of LDLs 24
Cell culture 24
MTT assay 25
Western blotting 25
Intracellular calcium release analysis 25
Biomolecular Interaction Analysis System 26
Data Analysis and Statistics 26
Ⅳ. Results 27
LDL characterization 27
Effects of LDLs on endothelial cell proliferation 27
Expression of COX-2 by glycated-LDL in endothelial cell 27
Intracellular calcium release of EC219 or HUVEC by native-, nonglycated- and glycated-LDL 32
Phosphorylation of ERK by native-, nonglycated- and glycated-LDL 32
Glycated-LDL-incuced ERK phosphorylation was modulated via Src kinase, Ras and MEK pathway 36
Phosphorylation of AKT by glycated-LDL 36
Glycated-LDL induce AKT activation in a PI3 Kinase-dependent pathway 36
Confirmation of IκB-α level by glycated-LDL 40
Comparison of binding rates of each LDL to β2 integrin(CD11c/CD18) 40
Ⅴ. Discussion 44
PART I 44
PART II 48
Ⅵ. References 50
Abstracts (in Korean) 56
감사의 글 58
1. Events in atherosclerotic plaque formation 14
2. Participation of inflammation in all stages of atherosclerosis 15
3. Steps in atheroma formation and progression 16
4. Chemical reaction leading to the formation of advanced glycation endproducts 17
5. A scheme of signaling pathway connected with the proliferation and inflammation of endothelial cell by modified-LDL 19
6. Features of 2 integrins 21
7. Electrophoretic mobility of native-, nonglycated-and glycated-LDL by agarose gel electrophoresis 28
8. Comparision of lipid peroxidation of native-, nonglycated-and glycated-LDL by TBARS 29
9. Effect of native-, nonglycated- and glycated-LDL on EC219 proliferation 30
10. Time- or dose-dependent course of COX-2 expression by glycated-LDL in EC219 31
11. Intracellular calcium release of EC219 and HUVEC by native nonglycated-and glycated-LDL, 33
12. Induction of ERK phosphorylation by glycated-LDL in a time-dependent course 34
13. Effects of ERK phosphorylation by LDLs in a dose-dependent experiments 35
14. Glycated LDL-induced ERK phosphorylation was significantly inhibited by Src kinase, Ras and MEK inhibitor 37
15. Induction of AKT phosphorylation by glycated-LDL in EC219 38
16. Glycated-LDL-induced AKT phosphorylation was significantly inhibited by a Src kinase inhibitor and PI3-K inhibitor 39
17. Level of IκB-α by glycated-LDL in a time-dependent manner 41
18. Comparison of binding of native(N0)-, nonglycated(N10)-and glycated(G10)-LDL to β2 integrin(CD11c/CD18) 42
19. Binding rate of G60-LDL to β2 integrin(CD11c/CD18) 43
20. Proposed signal pathway of COX-2 expression by glycated-LDL on EC219 47
1. Major integrin pairing 22
2. Specific ligands of CD11/CD18(β2 integrin) 23
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