A critical review of the literature on acrolein toxicity

Ro, Beauchamp; Da, Andjelkovich; Ad, Kligerman; Kt, Morgan; Hd, Heck

doi:10.3109/10408448509037461

Cited by 251 publications

(141 citation statements)

References 325 publications

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“…Acrolein-induced toxicity has previously been reviewed by Beauchamp et al [92] and by Kehrer and Biswal [93]. Numerous studies indicate that acrolein-induced toxic effects can at least to some extent be rationalized by depletion of cellular GSH [93].…”

Section: Acrolein Adduction To Amino Acids and Cross-linking Of Proteinsmentioning

confidence: 99%

Acrolein: Sources, metabolism, and biomolecular interactions relevant to human health and disease

Stevens

Maier

2008

Molecular Nutrition Food Res

619

634

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Acrolein (2-propenal) is ubiquitously present in (cooked) foods and in the environment. It is formed from carbohydrates, vegetable oils and animal fats, amino acids during heating of foods, and by combustion of petroleum fuels and biodiesel. Chemical reactions responsible for release of acrolein include heat-induced dehydration of glycerol, retro-aldol cleavage of dehydrated carbohydrates, lipid peroxidation of polyunsaturated fatty acids, and Strecker degradation of methionine and threonine. Smoking of tobacco products equals or exceeds the total human exposure to acrolein from all other sources. The main endogenous sources of acrolein are myeloperoxidase-mediated degradation of threonine and amine oxidase-mediated degradation of spermine and spermidine, which may constitute a significant source of acrolein in situations of oxidative stress and inflammation. Acrolein is metabolized by conjugation with glutathione and excreted in the urine as mercapturic acid metabolites. Acrolein forms Michael adducts with ascorbic acid in vitro, but the biological relevance of this reaction is not clear. The biological effects of acrolein are a consequence of its reactivity towards biological nucleophiles such as guanine in DNA and cysteine, lysine, histidine, and arginine residues in critical regions of nuclear factors, proteases, and other proteins. Acrolein adduction disrupts the function of these biomacromolecules which may result in mutations, altered gene transcription, and modulation of apoptosis.

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Section: Acrolein Adduction To Amino Acids and Cross-linking Of Proteinsmentioning

confidence: 99%

Acrolein: Sources, metabolism, and biomolecular interactions relevant to human health and disease

Stevens

Maier

2008

Molecular Nutrition Food Res

619

634

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“…Acrolein (CH2=CH-CHO) is an acrid smelling environmental pollutant that is formed during combustion of organic and plastic substances (36). It is also generated as a natural metabolite during oxidative stress mediated lipid peroxidation.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2007

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Oxidative damage to proteins such as apolipoprotein B100 increases the atherogenicity of low density lipoproteins (LDL). However, little is known about the potential oxidative damage to apolipoprotein E (apoE), an exchangeable anti-atherogenic apolipoprotein. ApoE plays an integral role in lipoprotein metabolism by regulating the plasma cholesterol and triglyceride levels. Hepatic uptake of lipoproteins is facilitated by apoE's ability to bind with cell surface heparan sulfate proteoglycans and to lipoprotein receptors via basic residues in its 22 kDa N-terminal domain (NT). We investigated the effect of acrolein, an aldehydic product of endogenous lipid peroxidation and a tobacco smoke component, on the conformation and function of recombinant human apoE3-NT. Acrolein caused oxidative modification of 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 and the LDL receptor. Furthermore, acrolein-modified apoE3-NT displayed a 5-fold decrease in its ability to interact 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 observations have implications regarding the role of apoE in the pathogenesis of smoking-and oxidative stress-mediated cardiovascular and cerebrovascular diseases. KeywordsCardiovascular disease; apolipoprotein E; acrolein; tobacco smoke; oxidative stress; aging; LDL receptor; heparan sulfate proteoglycan; lysine modification Oxidative stress is recognized as a major factor in the onset of atherosclerosis, cardiovascular disease and stroke in humans; of several factors that lead to increased oxidative stress, aging and life style (diet, smoking) play crucial roles. Atherosclerosis is characterized by the intracellular and extra cellular deposition of low density lipoproteins (LDL) in macrophages (1). Oxidative modification of plasma LDL leads to their uptake by scavenger receptors located The role of apoE in cholesterol metabolism emerged from studies with transgenic mice over expressing apoE, which manifested decreased plasma cholesterol levels on a chow diet and a marked resistance to hypercholesterolemia when fed a cholesterol rich diet (4). On the other hand, apoE-deficient subjects develop symptoms of type III hyperlipoproteinemia (5), with elevated plasma cholesterol levels and accumulation of particles bearing size in the very low density lipoprotein (VLDL) and intermediate density lipoprotein (IDL) range (6,7). Further, inactivation of apoE by gene targeting leads to accumulation of cholesterol-rich remnant lipoproteins and spontaneous atherosclerotic lesions in mice (8,9). Taken together, these early studies have established the key role of apoE in regulating plasma cholesterol and triglyceride levels, which are recognized as indicators of heart disease. The focus of this study is to investigate the role ...

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“…Acrolein is produced exogenously as a product of organic combustion and endogenously as a product of lipid peroxidation (5)(6)(7). Acrolein also arises during cyclophosphamide metabolism (8).…”

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confidence: 99%

Evaluation of the Mutagenic Potential of the Principal DNA Adduct of Acrolein

VanderVeen

Hashim²,

Nechev

et al. 2001

Journal of Biological Chemistry

104

129

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Acrolein is produced extensively in the environment by incomplete combustion of organic materials, and it arises endogenously in humans as a metabolic by-product. Acrolein reacts with DNA at guanine residues to form the exocyclic adduct, 8-hydroxypropanodeoxyguanosine (HOPdG). Acrolein is mutagenic, and a correlation exists between HOPdG levels in Salmonella typhimurium treated with acrolein and a resultant increase in mutation frequency. Site-specifically modified oligonucleotides were used to explore the mutagenic potential of HOPdG in Escherichia coli strains that were either wild-type for repair or deficient in nucleotide excision repair or base excision repair. Oligonucleotides modified with HOPdG were inserted into double-stranded bacteriophage vectors using the gapped-duplex method or into single-stranded bacteriophage vectors and transformed into SOS-induced E. coli strains. Progeny phage were analyzed by oligonucleotide hybridization to establish the mutation frequency and the spectrum of mutations produced by HOPdG. The correct base, dCMP, was incorporated opposite HOPdG in all circumstances tested. In contrast, in vitro lesion bypass studies showed that HOPdG causes misincorporation opposite the modified base and is a block to replication. The combination of these studies showed that HOPdG is not miscoding in vivo at the level of sensitivity of these site-specific mutagenesis assays.

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A critical review of the literature on acrolein toxicity

Cited by 251 publications

References 325 publications

Acrolein: Sources, metabolism, and biomolecular interactions relevant to human health and disease

Acrolein: Sources, metabolism, and biomolecular interactions relevant to human health and disease

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

Evaluation of the Mutagenic Potential of the Principal DNA Adduct of Acrolein

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