Toxicological Sciences 57, 6-15 (2000)
Copyright © 2000 by the Society of Toxicology
Forum |
The Molecular Effects of Acrolein
Division of Pharmacology and Toxicology, College of Pharmacy, The University of Texas at Austin, Austin, Texas 78712
ABSTRACT
Acrolein is a highly electrophilic 
,ß-unsaturated aldehyde to which humans are exposed in a variety of environmental situations, particularly as a component of smoke. In addition, as a metabolite of cyclophosphamide, acrolein is a major factor in the toxicity and perhaps the therapeutic activity of this important anticancer agent. The exposures to acrolein that are attained in vivo in most situations are quite low and the effects may differ from those seen at acutely toxic doses. At low doses, acrolein inhibits cell proliferation without causing cell death and may enhance apoptosis from secondary toxins, while at higher doses oncosis ensues. Although the acute toxicology of acrolein has been extensively investigated, both in animals and cultured cells, little information exists on the molecular effects of this reactive aldehyde. It is possible that the acrolein-mediated decrease in cell proliferation is caused by effecting changes in the expression of one or more growth- or stress-related genes or transcription factors secondary to a reduction in glutathione (GSH), which is rapidly depleted following acrolein treatment. It is apparent that the activation of the transcription factors nuclear factor kappa B (NF-
B) and activator protein 1 (AP-1) can be inhibited by acrolein. The purpose of this review is to assess the literature currently available on the molecular effects of acrolein, to discuss the relationship between effects on glutathione with those on various genes, and to present some new data showing that acrolein actively stimulates genes associated with the electrophile response element.
Key Words: acrolein; nuclear factor kappa-B (NF-B); activator protein 1 (AP-1); glutathione GSH); transcription factors; electrophile response element (ERE); gene array.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  M. T. Borchers, S. C. Wesselkamper, B. L. Eppert, G. T. Motz, M. A. Sartor, C. R. Tomlinson, M. Medvedovic, and J. W. Tichelaar Nonredundant Functions of {alpha}{beta} and {gamma}{delta} T Cells in Acrolein-Induced Pulmonary Pathology Toxicol. Sci., September 1, 2008; 105(1): 188 - 199. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. M. LoPachin, D. S. Barber, and T. Gavin Molecular Mechanisms of the Conjugated {alpha},{beta}-Unsaturated Carbonyl Derivatives: Relevance to Neurotoxicity and Neurodegenerative Diseases Toxicol. Sci., August 1, 2008; 104(2): 235 - 249. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. I. Kasahara, M. E. Poynter, Z. Othman, D. Hemenway, and A. van der Vliet Acrolein Inhalation Suppresses Lipopolysaccharide-Induced Inflammatory Cytokine Production but Does Not Affect Acute Airways Neutrophilia J. Immunol., July 1, 2008; 181(1): 736 - 745. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Zhu, L. Zhang, A. R. Amin, and Y. Li Coordinated Upregulation of a Series of Endogenous Antioxidants and Phase 2 Enzymes as a Novel Strategy for Protecting Renal Tubular Cells from Oxidative and Electrophilic Stress Experimental Biology and Medicine, June 1, 2008; 233(6): 753 - 765. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Zhu, Z. Jia, L. Zhang, M. Yamamoto, H. P. Misra, M. A. Trush, and Y. Li Antioxidants and Phase 2 Enzymes in Macrophages: Regulation by Nrf2 Signaling and Protection Against Oxidative and Electrophilic Stress Experimental Biology and Medicine, April 1, 2008; 233(4): 463 - 474. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. S. Deshmukh, C. Shaver, L. M. Case, M. Dietsch, S. C. Wesselkamper, W. D. Hardie, T. R. Korfhagen, M. Corradi, J. A. Nadel, M. T. Borchers, et al. Acrolein-Activated Matrix Metalloproteinase 9 Contributes to Persistent Mucin Production Am. J. Respir. Cell Mol. Biol., April 1, 2008; 38(4): 446 - 454. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Zhang and H. J. Forman Acrolein Induces Heme Oxygenase-1 through PKC-{delta} and PI3K in Human Bronchial Epithelial Cells Am. J. Respir. Cell Mol. Biol., April 1, 2008; 38(4): 483 - 490. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S.-i. Kim, G. P. Pfeifer, and A. Besaratinia Lack of Mutagenicity of Acrolein-Induced DNA Adducts in Mouse and Human Cells Cancer Res., December 15, 2007; 67(24): 11640 - 11647. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Facchinetti, F. Amadei, P. Geppetti, F. Tarantini, C. Di Serio, A. Dragotto, P. M. Gigli, S. Catinella, M. Civelli, and R. Patacchini {alpha},beta-Unsaturated Aldehydes in Cigarette Smoke Release Inflammatory Mediators from Human Macrophages Am. J. Respir. Cell Mol. Biol., November 1, 2007; 37(5): 617 - 623. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y.-M. Go, P. J. Halvey, J. M. Hansen, M. Reed, J. Pohl, and D. P. Jones Reactive Aldehyde Modification of Thioredoxin-1 Activates Early Steps of Inflammation and Cell Adhesion Am. J. Pathol., November 1, 2007; 171(5): 1670 - 1681. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Bodo, D. J. Tobin, Y. Kamenisch, T. Biro, M. Berneburg, W. Funk, and R. Paus Dissecting the Impact of Chemotherapy on the Human Hair Follicle: A Pragmatic in Vitro Assay for Studying the Pathogenesis and Potential Management of Hair Follicle Dystrophy Am. J. Pathol., October 1, 2007; 171(4): 1153 - 1167. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Zu, R. Yan, S. Robbins, P. A. Krishack, D.-F. Liao, and D. Cao Reduced 293T Cell Susceptibility to Acrolein Due to Aldose Reductase-like-1 Protein Expression Toxicol. Sci., June 1, 2007; 97(2): 562 - 568. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Tanel and D. A. Averill-Bates Inhibition of Acrolein-Induced Apoptosis by the Antioxidant N-Acetylcysteine J. Pharmacol. Exp. Ther., April 1, 2007; 321(1): 73 - 83. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. M. LoPachin, D. S. Barber, B. C. Geohagen, T. Gavin, D. He, and S. Das Structure-Toxicity Analysis of Type-2 Alkenes: In Vitro Neurotoxicity Toxicol. Sci., January 1, 2007; 95(1): 136 - 146. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. M. LoPachin and D. S. Barber Synaptic Cysteine Sulfhydryl Groups as Targets of Electrophilic Neurotoxicants Toxicol. Sci., December 1, 2006; 94(2): 240 - 255. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Rahman and I. M. Adcock Oxidative stress and redox regulation of lung inflammation in COPD. Eur. Respir. J., July 1, 2006; 28(1): 219 - 242. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Biswal, T. Maxwell, T. Rangasamy, and J. P. Kehrer Modulation of benzo[a]pyrene-induced p53 DNA activity by acrolein Carcinogenesis, August 1, 2003; 24(8): 1401 - 1406. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. L. Tsakadze, S. Srivastava, S. O. Awe, A. S. O. Adeagbo, A. Bhatnagar, and S. E. D'Souza Acrolein-induced vasomotor responses of rat aorta Am J Physiol Heart Circ Physiol, July 11, 2003; 285(2): H727 - H734. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. A. Tacka, J. C. Dabrowiak, J. Goodisman, and A.-K. Souid Kinetic Analysis of the Reactions of 4-Hydroperoxycyclophosphamide and Acrolein With Glutathione, Mesna, and Wr-1065 Drug Metab. Dispos., August 1, 2002; 30(8): 875 - 882. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L Mazur, A Czyzewska, and M Bochenek Flow cytometric detection of apoptotic bone marrow cells with fractional DNA content after application of WR-2721, cyclophosphamide, cisplatin, and exposure of mice to gamma rays Human and Experimental Toxicology, June 1, 2002; 21(6): 335 - 341. [Abstract] [PDF]
|
|
|
|
 |
|
 E. I. Finkelstein, M. Nardini, and A. van der Vliet Inhibition of neutrophil apoptosis by acrolein: a mechanism of tobacco-related lung disease? Am J Physiol Lung Cell Mol Physiol, September 1, 2001; 281(3): L732 - L739. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. M. Freed, Y. Ouyang, and J. M. McCue Mechanisms of Altered Transcription by Cigarette Smoke Toxicol. Sci., January 1, 2001; 59(1): 1 - 2. [Abstract] [Full Text] [PDF]
|
|