Reaction of tobacco smoke aldehydes with human hemoglobin

Hoberman, Henry D.; George, Richard C. San

doi:10.1002/jbt.2570030205

Cited by 39 publications

(23 citation statements)

References 20 publications

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“…Acrolein and 4-hydroxynonenal, another ␣,␤-unsaturated aldehyde produced by lipid oxidation, have been proposed to cross-link HDL proteins (30,50). Using SDS-PAGE, we confirmed that proteins with higher apparent M r values appeared when apoA-I or HDL was exposed to acrolein.…”

Section: Discussionsupporting

confidence: 56%

Acrolein Impairs ATP Binding Cassette Transporter A1-dependent Cholesterol Export from Cells through Site-specific Modification of Apolipoprotein A-I

Shao

McDonald

et al. 2005

Journal of Biological Chemistry

110

125

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Acrolein is a highly reactive ␣,␤-unsaturated aldehyde, but the factors that control its reactions with nucleophilic groups on proteins remain poorly understood. Lipid peroxidation and threonine oxidation by myeloperoxidase are potential sources of acrolein during inflammation. Because both pathways are implicated in atherogenesis and high density lipoprotein (HDL) is anti-atherogenic, we investigated the possibility that acrolein might target the major protein of HDL, apolipoprotein A-I (apoA-I), for modification. Tandem mass spectrometric analysis demonstrated that lysine 226, located near the center of helix 10 in apoA-I, was the major site modified by acrolein. Importantly, this region plays a critical role in the cellular interactions and ability of apoA-I to transport lipid. Indeed, we found that conversion of Lys-226 to N ⑀ -(3-methylpyridinium)lysine by acrolein associated quantitatively with decreased cholesterol efflux from cells via the ATP-binding cassette transporter A1 pathway. In the crystal structure of truncated apoA-I, Glu-234 lies adjacent to Lys-226, suggesting that negatively charged residues might direct the modification of specific lysine residues in proteins. Finally, immunohistochemical studies with a monoclonal antibody revealed co-localization of apoA-I with acrolein adducts in human atherosclerotic lesions. Our observations suggest that acrolein might interfere with normal reverse cholesterol transport by HDL by modifying specific sites in apoA-I. Thus, acrolein might contribute to atherogenesis by impairing cholesterol removal from the artery wall.Chemical damage to key proteins may contribute to the pathogenesis of many disorders, including diabetes, Alzheimer disease, and ischemiareperfusion injury and perhaps to the aging process itself (1). Reactive aldehydes are an important class of agents that covalently modify proteins, and a variety of enzymatic and nonenzymatic mechanisms generate them in the body (2). Acrolein is the most reactive ␣,␤-unsaturated aldehyde, and it rapidly modifies biological nucleophiles (3). This potent electrophile may be produced in the body through lipid peroxidation or peroxidation of threonine by myeloperoxidase, and high levels are found in cigarette smoke (4 -6). Lipid peroxidation, myeloperoxidase, renal disease, and cigarette smoking all strongly associate with an increased risk of vascular disease (2,7,8). Moreover, epitopes recognized by a monoclonal antibody specific for lysine adducts of acrolein have been detected in macrophages of atherosclerotic lesions (4), raising the possibility that acrolein is one important agent for damaging proteins in the artery wall. Acrolein may also be a uremic toxin, and carbonyl stress appears to increase in patients with chronic renal failure (9).Like other ␣,␤-unsaturated aldehydes, acrolein selectively reacts with the sulfhydryl group of cysteine, the imidazole group of histidine, and the ⑀-amino group of lysine (10 -12). Indirect evidence suggests that it might also modify arginine (13). In vitro studies ha...

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Section: Discussionsupporting

confidence: 56%

Acrolein Impairs ATP Binding Cassette Transporter A1-dependent Cholesterol Export from Cells through Site-specific Modification of Apolipoprotein A-I

Shao

McDonald

et al. 2005

Journal of Biological Chemistry

110

125

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“…The authors have also noted that the formation of the intramolecular aldimine bond should be favored by entropic factors. This proposition may be supported by the fact that acrolein has been widely used as a cross-linking reagent in protein chemistry to link covalently different subunits in oligomeric proteins (28).…”

Section: Fig 4 Esi-lc/ms Analysis Of Acrolein-lysine Adductmentioning

confidence: 99%

Nϵ-(3-Methylpyridinium)lysine, a Major Antigenic Adduct Generated in Acrolein-modified Protein

Furuhata

Ishii

Kumazawa

et al. 2003

Journal of Biological Chemistry

106

115

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Acrolein, a representative carcinogenic aldehyde, that could be ubiquitously generated in biological systems under oxidative stress shows facile reactivity with a nucleophile such as a protein. In this study, to gain a better understanding of the molecular basis of acrolein modification of protein, we characterized the acrolein modification of a model peptide (the oxidized B chain of insulin) by electrospray ionization-liquid chromatography/mass spectrometry method and established a novel acrolein-lysine condensation reaction. In addition, we found that this condensation adduct represented the major antigenic adduct generated in acrolein-modified protein. To identify the modification site and structures of adducts generated in the acrolein-modified insulin B chain, both the acrolein-pretreated and untreated peptides were digested with V8 protease and the resulting peptides were subjected to electrospray ionization-liquid chromatography/mass spectrometry. This technique identified nine peptides, which contained the acrolein adducts at Lys-29 and the N terminus, and revealed that the reaction of the insulin B chain with acrolein gave multiple adducts, including an unknown adduct containing two molecules of acrolein per lysine. To identify this adduct, we incubated N ␣ -acetyllysine with acrolein and isolated a product having the same molecular mass as the unknown acrolein-lysine adduct. On the basis of the chemical and spectroscopic evidence, the adduct was determined to be a novel pyridinium-type lysine adduct, N ⑀ -(3-methylpyridinium)lysine (MP-lysine). The formation of MP-lysine was confirmed by amino acid analysis of proteins treated with acrolein. More notably, this condensation adduct appeared to be an intrinsic epitope of a monoclonal antibody 5F6 that had been raised against acrolein-modified protein.Several lines of evidence indicate that the oxidative modification of protein and the subsequent accumulation of the modified proteins have been found in cells during aging and oxidative stress and in various pathological states including premature diseases, muscular dystrophy, rheumatoid arthritis, and atherosclerosis (1-4). The important agents that give rise to the modification of a protein may be represented by reactive aldehydic intermediates such as ketoaldehydes, 2-alkenals and 4-hydroxy-2-alkenals (3, 5, 6). These reactive aldehydes are considered important mediators of cell damage because of their ability to covalently modify biomolecules, which can disrupt important cellular functions and can cause mutations (5). Furthermore, the adduction of aldehydes to apolipoprotein B in low density lipoproteins has been strongly implicated in the mechanism by which low density lipoproteins is converted to an atherogenic form that is taken up by macrophages, leading to the formation of foam cells (7,8).Acrolein, an unpleasant and troublesome byproduct of overheated organic matter, occurs as a ubiquitous pollutant in the environment, e.g. the incomplete combustion of plastic materials, cigarette smoking, and over...

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“…Aldehydes are cytotoxic compounds due to their reactivity towards nucleophiles and sulphydryl groups of protein and nucleophilic acids or related amino acids. Consequently, in the body, they induce cell injury and death and result in several diseases such as atherosclerosis and cancer (Esterbauer, 1982;Hoberman & San George, 1988). In addition, cytotoxicity increases with increasing chain length of the aldehydes (Esterbauer, Zollner, & Schaur 1990).…”

Section: Introductionmentioning

confidence: 99%

Aldehyde formation in frozen mackerel (Scomber scombrus) in the presence and absence of instant green tea

2008

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Reaction of tobacco smoke aldehydes with human hemoglobin

Cited by 39 publications

References 20 publications

Acrolein Impairs ATP Binding Cassette Transporter A1-dependent Cholesterol Export from Cells through Site-specific Modification of Apolipoprotein A-I

Acrolein Impairs ATP Binding Cassette Transporter A1-dependent Cholesterol Export from Cells through Site-specific Modification of Apolipoprotein A-I

Nϵ-(3-Methylpyridinium)lysine, a Major Antigenic Adduct Generated in Acrolein-modified Protein

Aldehyde formation in frozen mackerel (Scomber scombrus) in the presence and absence of instant green tea

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