Skip to main content
Log in

Acrolein, an Environmental Toxin, Induces Cardiomyocyte Apoptosis via Elevated Intracellular Calcium and Free Radicals

  • Original Paper
  • Published:
Cell Biochemistry and Biophysics Aims and scope Submit manuscript

Abstract

Acrolein, an unsaturated aldehyde, is an environmental toxin known to inhibit mitochondrial electron transport chain in brain and induce lipid peroxidation and apoptosis. However, the nature of the effects of acrolein on cardiac function and myocardium is not known. The objective of this study is to examine whether acrolein induces apoptosis in cardiomyocytes and alters cytosolic calcium concentration and the intracellular oxygen free-radical levels. Adult mouse cardiomyocytes exposed to 1 μmol/l of acrolein showed a marked increase in the intracellular oxygen free-radicals and calcium concentration, by 12- and 2-fold, respectively, compared to the resting value. Moreover, the cardiomyocyte viability decreased significantly in a dose-dependent manner by treatment with 25, 50, and 100 μmol/l of acrolein compared to controls. Morphological changes and DNA laddering typical of apoptosis were found in acrolein-exposed cardiomyocytes. Our finding suggested that acrolein caused apoptotic death of adult mice cardiomyocytes by increasing intracellular oxygen free-radicals and calcium concentration.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Stevens, J. F., & Maier, C. S. (2008). Acrolein: sources, metabolism, and biomolecular interactions relevant to human health and disease. Molecular Nutrition & Food Research, 52, 7–25.

    Article  CAS  Google Scholar 

  2. Uchida, K., Kanematsu, M., Morimitsu, Y., Osawa, T., Noguchi, N., et al. (1998). Acrolein is a product of lipid peroxidation reaction. Formation of free acrolein and its conjugate with lysine residues in oxidized low density lipoproteins. Journal of Biological Chemistry, 273, 16058–16066.

    Article  PubMed  CAS  Google Scholar 

  3. Wang, H., Liu, X., Umino, T., Skold, C. M., Zhu, Y., et al. (2001). Cigarette smoke inhibits human bronchial epithelial cell repair processes. American Journal of Respiratory Cell and Molecular Biology, 25, 772–779.

    PubMed  CAS  Google Scholar 

  4. Adams, J. D., Jr., & Klaidman, L. K. (1993). Acrolein-induced oxygen radical formation. Free Radical Biology and Medicine, 15, 187–193.

    Article  PubMed  CAS  Google Scholar 

  5. Nardini, M., Finkelstein, E. I., Reddy, S., Valacchi, G., Traber, M., et al. (2002). Acrolein-induced cytotoxicity in cultured human bronchial epithelial cells. Modulation by alpha-tocopherol and ascorbic acid. Toxicology, 170, 173–185.

    Article  PubMed  CAS  Google Scholar 

  6. Toraason, M., Luken, M. E., Breitenstein, M., Krueger, J. A., & Biagini, R. E. (1989). Comparative toxicity of allylamine and acrolein in cultured myocytes and fibroblasts from neonatal rat heart. Toxicology, 56, 107–117.

    Article  PubMed  CAS  Google Scholar 

  7. Biagini, R. E., Toraason, M. A., Lynch, D. W., & Winston, G. W. (1990). Inhibition of rat heart mitochondrial electron transport in vitro: implications for the cardiotoxic action of allylamine or its primary metabolite, acrolein. Toxicology, 62, 95–106.

    Article  PubMed  CAS  Google Scholar 

  8. Wolska, B. M., & Solaro, R. J. (1996). Method for isolation of adult mouse cardiac myocytes for studies of contraction and microfluorimetry. American Journal of Physiology, 271, H1250–H1255.

    PubMed  CAS  Google Scholar 

  9. Mattson, M. P., Barger, S. W., Begley, J. G., & Mark, R. J. (1995). Calcium, free radicals, and excitotoxic neuronal death in primary cell culture. Methods in Cell Biology, 46, 187–216.

    Article  PubMed  CAS  Google Scholar 

  10. Kenichi, H., Yoichiro, K., Makoto, K., Masato, K., Satoshi, K., et al. (2002). Use of tetanus to investigate myofibrillar responsiveness to Ca2+ in isolated mouse ventricular myocytes. Japanese Journal of Physiology, 52, 121–127.

    Article  Google Scholar 

  11. Ishiyama, M., Miyazono, Y., Sasamoto, K., Ohkura, Y., & Ueno, K. (1997). A highly water-soluble disulfonated tetrazolium salt as a chromogenic indicator for NADH as well as cell viability. Talanta, 44, 1299–1305.

    Article  PubMed  CAS  Google Scholar 

  12. Herrmann, M., Lorenz, H. M., Voll, R., Grunke, M., Woith, W., et al. (1994). A rapid and simple method for the isolation of apoptotic DNA fragments. Nucleic Acids Research, 22, 5506–5507.

    Article  PubMed  CAS  Google Scholar 

  13. Jaeschke, H., Kleinwaechter, C., & Wendel, A. (1987). The role of acrolein in allyl alcohol-induced lipid peroxidation and liver cell damage in mice. Biochemical Pharmacology, 36, 51–57.

    Article  PubMed  CAS  Google Scholar 

  14. Awasthi, S., & Boor, P. J. (1994). Lipid peroxidation and oxidative stress during acute allylamine-induced cardiovascular toxicity. Journal of Vascular Research, 31, 33–41.

    PubMed  CAS  Google Scholar 

  15. Conklin, D. J., Bhatnagar, A., Cowley, H. R., Johnson, G. H., Wiechmann, R. J., et al. (2006). Acrolein generation stimulates hypercontraction in isolated human blood vessels. Toxicology and Applied Pharmacology, 217, 277–288.

    Article  PubMed  CAS  Google Scholar 

  16. Conklin, D. J., Langford, S. D., & Boor, P. J. (1998). Contribution of serum and cellular semicarbazide-sensitive amine oxidase to amine metabolism and cardiovascular toxicity. Toxicological Sciences, 46, 386–392.

    Article  PubMed  CAS  Google Scholar 

  17. Nelson, T. J., & Boor, P. J. (1982). Allylamine cardiotoxicity–IV. Metabolism to acrolein by cardiovascular tissues. Biochemical Pharmacology, 31, 509–514.

    Article  PubMed  CAS  Google Scholar 

  18. Josephson, R. A., Silverman, H. S., Lakatta, E. G., Stern, M. D., & Zweier, J. L. (1991). Study of the mechanisms of hydrogen peroxide and hydroxyl free radical-induced cellular injury and calcium overload in cardiac myocytes. Journal of Biological Chemistry, 266, 2354–2361.

    PubMed  CAS  Google Scholar 

  19. Trebak, M., Ginnan, R., Singer, H. A., & Jourd’heuil, D. (2010). Interplay between calcium and reactive oxygen/nitrogen species: an essential paradigm for vascular smooth muscle signaling. Antioxidants & Redox Signaling, 12, 657–674.

    Article  CAS  Google Scholar 

  20. Kaneko, M., Elimban, V., & Dhalla, N. S. (1989). Mechanism for depression of heart sarcolemmal Ca2+ pump by oxygen free radicals. American Journal of Physiology, 257, H804–H811.

    PubMed  CAS  Google Scholar 

  21. Katz, A. M., & Reuter, H. (1979). Cellular calcium and cardiac cell death. American Journal of Cardiology, 44, 188–190.

    Article  PubMed  CAS  Google Scholar 

  22. Garlick, P. B., Davies, M. J., Hearse, D. J., & Slater, T. F. (1987). Direct detection of free radicals in the reperfused rat heart using electron spin resonance spectroscopy. Circulation Research, 61, 757–760.

    PubMed  CAS  Google Scholar 

  23. Pan, J., Keffer, J., Emami, A., Ma, X., Lan, R., et al. (2009). Acrolein-derived DNA adduct formation in human colon cancer cells: its role in apoptosis induction by docosahexaenoic acid. Chemical Research in Toxicology, 22, 798–806.

    Article  PubMed  CAS  Google Scholar 

  24. Roy, J., Pallepati, P., Bettaieb, A., Tanel, A., & Averill-Bates, D. A. (2009). Acrolein induces a cellular stress response and triggers mitochondrial apoptosis in A549 cells. Chemico-Biological Interactions, 181, 154–167.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This study was supported by Department of Biochemistry and Cardiovascular Medicine, Osaka University Graduate School of Medicine, Japan. The authors acknowledge the fellowship provided by China Scholarship Council (CSC) (No. 22821173) and Japanese Government Scholarship.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Lijuan Wang.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wang, L., Sun, Y., Asahi, M. et al. Acrolein, an Environmental Toxin, Induces Cardiomyocyte Apoptosis via Elevated Intracellular Calcium and Free Radicals. Cell Biochem Biophys 61, 131–136 (2011). https://doi.org/10.1007/s12013-011-9169-5

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12013-011-9169-5

Keywords

Navigation