[제 3 주제] Role of glycation and lipid peroxidation of low-density lipoprotein in pathophysiology of diabetic angiopathy

• 영문명: [제 3 주제] Role of glycation and lipid peroxidation of low-density lipoprotein in pathophysiology of diabetic angiopathy
• 발행기관: 인제대학교 식품과학연구소
• 저자명: Noriyuki Sakata
• 간행물 정보: 『인제식품과학 FORUM 논총』제9회, 45~81쪽, 전체 37쪽
• 주제분류: 자연과학 > 생활/식품과학
• 파일형태: PDF
• 발행일자: 2002.04.01

영문 초록

Glycation of proteins and dyslipidemia contributes to the development of diabetic complications, including macro- and microangiopathies. Recently, glycation and oxidation reaction has been shown to share a common pathway, resulting in the formation of glycoxidative products, such as carboxymethyllysine (CML) and pentosidine. In this study, we evaluated the role of glycation and lipid peroxidation of low-density lipoprotein (LDL) in the development of pathophysiology in diabetic angiopathy. Immunochemical analysis showed that CML was formed by in vitro glycoxidation of LDL, but not by oxidation and non-oxidative glycation of LDL. In contrast, malondialdehyde (MDA) formation was observed in both oxidation and glycoxidation of LDL, but not in non-oxidative glycation of LDL. Hexitol-Iysine (HL), an Amadori product, was formed by non-oxidative glycation and glycoxidation of LDL, but not by oxidation of LDL. Immunohistochemical analysis showed that macrophage/foam cells in atherosclerotic and diabetic glomerular lesions accumulated glycoxidation and lipid peroxidation products, and expressed macrophage scavenger receptor class A. These results suggest that glycoxidation and lipid peroxidation of LDL synergistically promote the development of diabetic macro- and microangiopathies through interaction with macrophage scavenger receptor. However, there are various antioxidant agents in our body, which include superoxide dismutase, catalase and serum albumin. Human serum albumin (HSA) is the most abundant protein in the circulation and undergoes enhanced glycation and oxidation in diabetic patients. Therefore, decreased antioxidant activity of glycated and oxidized HSA may be involved in enhancement of lipid peroxidation of LDL in diabetic patients. We further examined the antioxidant activity of modified HSA to LDL oxidation. Native HSA showed a strong antioxidant activity to copper-induced oxidation of LDL, as evidenced by complete inhibition of MDA in the presence of more than 1 mg/ml of HSA. In contrast, in vitro glycoxidation induced the lowest antioxidant activity of HSA to LDL oxidation among various modifications. Oxidative HSA showed a moderate decrease in antioxidant activity. These results indicate that enhanced lipid peroxidation of LDL may be caused by not only glycoxidation of LDL, but also the decrease in the antioxidant activity of glycoxidative serum albumin. In conclusion, hyperglycemia in diabetic patients induces increased nonenzymatic chemical reaction between sugar and various proteins, and enhances oxidative stress. Consequently, glycoxidative and oxidative LDLs are increased in blood and accumulated in tissues. Macrophages incorporate these LDLs, and subsequently undergo cellular activation, leading to cell proliferation and matrix accumulation. These events may contribute to the development of diabetic macro- and micro-angiopathies.

목차

Abstract

Introduction

Materials and methods

Results

Discussion

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