The aldehyde acrolein induces apoptosis via activation of the mitochondrial pathway

Tanel, André; Averill‐Bates, Diana A.

doi:10.1016/j.bbamcr.2004.11.007

Cited by 88 publications

(59 citation statements)

References 46 publications

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“…Lipid aldehydes (e.g. acrolein, 4-hydroxynonenal, malondialdehyde), produced as a consequence of lipid peroxidation reactions, are believed to be important mediators of oxidative stress and can induce cell death by activating both the mitochondrial and death receptor pathways of apoptosis [38,39]. ALEs and their precursors have been implicated in macrovascular endothelium dysfunction and atheromatous lesion formation [27], but their precise role in the development of diabetic microvascular complications remains unresolved.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of N ε-(3-formyl-3,4-dehydropiperidino)lysine as a novel biomarker for the severity of diabetic retinopathy

et al. 2008

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Aims/hypothesis Recent studies suggest that oxidative stress should be monitored alongside HbA 1c to identify subgroups of diabetic patients at high risk of initiation or progression of retinopathy. The acrolein-derived advanced lipoxidation end-product (ALE), N " -(3-formyl-3,4-dehydropiperidino)lysine (FDP-lysine), is a useful biomarker that reflects the cumulative burden of oxidative stress over long periods of time. The purpose of the present study was to investigate whether serum and haemoglobin levels of FDP-lysine are associated with the severity of diabetic retinopathy in type 1 and type 2 diabetic patients. Methods Serum and haemoglobin levels of FDP-lysine were measured by competitive ELISA in 59 type 1 and 76 type 2 diabetic patients with no retinopathy, non-proliferative retinopathy or proliferative retinopathy (mean age [±SEM] 54.3±1.3 years), and in 47 non-diabetic control individuals (mean age 51.9±2.1 years).Results Serum and haemoglobin levels of FDP-lysine were significantly increased in diabetic patients compared with control individuals (p=0.04 and p=0.002, respectively). However, no significant association was found between levels of serum FDP-lysine and the severity of diabetic retinopathy (p=0.97). In contrast, increased haemoglobin FDP-lysine levels were observed in patients with proliferative retinopathy compared with patients without retinopathy and with non-proliferative retinopathy (p=0.04). The relationship of FDP-lysine with proliferative retinopathy was unaltered after adjustment for HbA 1c , or other clinical parameters. Conclusions/interpretation Our data suggest that haemoglobin FDP-lysine may provide a useful risk marker for the development of proliferative diabetic retinopathy independently of HbA 1c , and that elevated intracellular ALE formation may be involved in the pathogenesis of this sight-threatening complication of diabetes.

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Section: Discussionmentioning

confidence: 99%

Evaluation of N ε-(3-formyl-3,4-dehydropiperidino)lysine as a novel biomarker for the severity of diabetic retinopathy

et al. 2008

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“…Acrolein can either induce apoptosis [82,125] or have an inhibitory effect on apoptotic pathways as observed for human neutrophils [126]. Acrolein induced apoptosis in human lung epithelial (HBE1) cells at 10-25-μM and in isolated human alveolar macrophages at 25-μM exposure, as indicated by DNA fragmentation after 24 h of exposure.…”

Section: Acrolein Induces Necrotic and Apoptotic Cell Deathmentioning

confidence: 94%

“…Acrolein has also been reported to cause necrotic cell death when proB lymphoid cells were exposed to acrolein at concentrations greater than 10 μM in the culture medium lacking serum [127]. Averill-Bates and colleagues [125,128] demonstrated that acrolein can induce apoptosis in Chinese hamster ovary (CHO) cells, either through the intrinsic pathway which involves cytochrome c release [125] or through the extrinsic pathway by activation of death receptors [128]. Differences in cell types, cell culture conditions, medium composition, and acrolein concentration may explain some of the variable findings.…”

Section: Acrolein Induces Necrotic and Apoptotic Cell Deathmentioning

confidence: 97%

“…How can acrolein direct cellular death pathways, apoptosis versus necrosis? Tanel and Averill-Bates [125] have observed during their studies on apoptotic pathways in CHO cells that procaspase-3 was proteolytically processed but that caspase-3 was not catalytically active. Finkelstein et al [126] reported that exposure of human neutrophils to acrolein also prevented the activation of caspase-3.…”

Section: Acrolein Induces Necrotic and Apoptotic Cell Deathmentioning

confidence: 99%

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

Stevens

Maier

2008

Molecular Nutrition Food Res

630

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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“…It is known to induce apoptosis in several cell types such as keratinocytes (Takeuchi et al, 2001), neutrophils (Finkelstein et al, 2005), cultured neurons (Pugazhenthi et al, 2006), and Chinese hamster ovary (CHO) cells (Tanel and Averill-Bates, 2005), whereas necrosis occurs in others (Luo et al, 2005;Liu-Snyder et al, 2006).…”

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confidence: 99%

Inhibition of Acrolein-Induced Apoptosis by the AntioxidantN-Acetylcysteine

Tanel¹,

Averill‐Bates²

2007

J Pharmacol Exp Ther

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Acrolein is a highly electrophilic ␣,␤-unsaturated aldehyde to which humans are exposed in many situations. It is an environmental pollutant that is responsible for multiple respiratory diseases and has been implicated in neurodegenerative diseases such as Alzheimer's disease. The hypothesis of the study is that the antioxidant N-acetylcysteine (NAC), a precursor of glutathione, could protect cells against acrolein-induced apoptosis. Exposure of Chinese hamster ovary cells to a noncytotoxic dose of acrolein (4 fmol/cell) depleted intracellular glutathione to 45% of initial levels. NAC, which increased intracellular glutathione levels by 30%, afforded protection against acroleininduced cytotoxicity (loss of cell proliferation) and apoptosis. NAC protected against apoptosis by diminishing acroleininduced activation of the mitochondrial death pathway. NAC inhibited acrolein-induced Bad translocation from the cytosol to the mitochondria, as well as Bcl-2 translocation from mitochondria to the cytosol, as evaluated by Western blot analysis. However, NAC had no effect on acrolein-induced Bax translocation to mitochondria and cytochrome c liberation into the cytosol. Meanwhile, NAC inhibited depolarization of mitochondrial membrane potential, as evaluated by rhodamine fluorescence using flow cytometry. NAC also inhibited procaspase-9 processing, activation of enzymatic activity of caspase-9, -7, and -8, and poly(ADP-ribose) polymerase cleavage induced by acrolein. Inhibition of acrolein-induced apoptosis using NAC was confirmed morphologically by diminished condensation of nuclear chromatin, as evaluated by fluorescence microscopy. These findings suggest that NAC could be potentially useful as a protective agent for people exposed to acrolein.

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The aldehyde acrolein induces apoptosis via activation of the mitochondrial pathway

Cited by 88 publications

References 46 publications

Evaluation of N ε-(3-formyl-3,4-dehydropiperidino)lysine as a novel biomarker for the severity of diabetic retinopathy

Evaluation of N ε-(3-formyl-3,4-dehydropiperidino)lysine as a novel biomarker for the severity of diabetic retinopathy

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

Inhibition of Acrolein-Induced Apoptosis by the AntioxidantN-Acetylcysteine

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