Modification by Acrolein, a Component of Tobacco Smoke and Age-Related Oxidative Stress, Mediates Functional Impairment of Human Apolipoprotein E

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• 作者：Shiori Tamamizu-Kato ; Jason Yiu Wong ; Vikram Jairam ; Koji Uchida ; Vincent Raussens ; Hiroyuki Kato ; Jean-Marie Ruysschaert ; Vasanthy Narayanaswami
• 刊名：Biochemistry
• 出版年：2007
• 出版时间：July 17, 2007
• 年：2007
• 卷：46
• 期：28
• 页码：8392 - 8400
• 全文大小：222K
• 年卷期：v.46,no.28(July 17, 2007)
• ISSN：1520-4995

文摘

Oxidative damage to proteins such as apolipoprotein B-100 increases the atherogenicity oflow-density lipoproteins (LDL). However, little is known about the potential oxidative damage toapolipoprotein E (apoE), an exchangeable antiatherogenic apolipoprotein. ApoE plays an integral role inlipoprotein metabolism by regulating the plasma cholesterol and triglyceride levels. Hepatic uptake oflipoproteins is facilitated by apoE's ability to bind with cell surface heparan sulfate proteoglycans and tolipoprotein receptors via basic residues in its 22 kDa N-terminal domain (NT). We investigated the effectof acrolein, an aldehydic product of endogenous lipid peroxidation and a tobacco smoke component, onthe conformation and function of recombinant human apoE3-NT. Acrolein caused oxidative modificationof apoE3-NT as detected by Western blot with acrolein-lysine-specific antibodies, and tertiary conformational alterations. Acrolein modification impairs the ability of apoE3-NT to interact with heparin andthe LDL receptor. Furthermore, acrolein-modified apoE3-NT displayed a 5-fold decrease in its ability tointeract with lipid surfaces. Our data indicate that acrolein disrupts the functional integrity of apoE3,which likely interferes with its role in regulating plasma cholesterol homeostasis. These observationshave implications regarding the role of apoE in the pathogenesis of smoking- and oxidative stress-mediatedcardiovascular and cerebrovascular diseases.