Skip to main content
Log in

Role of ceramide in the aging-related decrease of cardiolipin content in the rat heart

  • Published:
Advances in Gerontology Aims and scope Submit manuscript

Abstract

Ceramide accumulation and a decrease of cardiolipin level in cardiomyocytes are among the key reasons of mitochondrial dysfunction and the emergence of heart failure. Ceramide has a significant effect on cardiolipin metabolism, and, therefore, the aim of the present study was to assess the role of ceramide in the aging-related decrease of cardiolipin content in the rat heart. Young (sexually mature), adult, and old (3-, 12-, 24-, 30-, and 34-month-old) Wistar male rats were used in the study. A considerable decrease in the content of cardiolipin during aging was accompanied by accumulation of phosphatidic acid, a precursor of cardiolipin. Doxorubicin administration to the rats or the perfusion of an isolated heart with a buffer solution supplemented with C16-ceramide evoked an increase in ceramide levels and a decrease in the level of cardiolipin in the heart of 3-month-old rats. The reduction of ceramide content in the hearts of 24-month-old rats by means of administration of melipramine and zoledronic acid that inhibit acidic sphingomyelinase led to an increase in cardiolipin levels. The results point at a certain contribution of sphingomyelinase-dependent ceramide accumulation to the aging-related decrease of cardiolipin content that can lead to disturbances of cardiac function. Acid sphingomyelinase and cardiolipin metabolism can be important targets in the treatment of aging-related cardiac pathology.

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.

Similar content being viewed by others

References

  1. Andrieu-Abadie, N., Jaffrezou, J.-P., Hatem, S., et al., L-carnitine prevents doxorubicin-induced apoptosis of cardiac myocytes: role of inhibition of ceramide generation, FASEB J., 1999, vol. 13, pp. 1501–1510.

    CAS  PubMed  Google Scholar 

  2. Argaud, L., Prigent, A.-F., Chalabreysse, L., et al., Ceramide in the antiapoptotic effect of ischemic preconditioning, Am. J. Physiol. Heart Circ. Physiol., 2004, vol. 286, pp. H246–H251.

    Article  CAS  PubMed  Google Scholar 

  3. Babenko, N.A., Garkavenko, V.V., Storozhenko, G.V., and Timofiychuk, O.A., Role of acid sphingomyelinase in the age-dependent dysregulation of sphingolipids turnover in the tissues of rats, Gen. Physiol. Biophys., 2016, vol. 35, no. 2, pp. 195–205.

    Article  CAS  PubMed  Google Scholar 

  4. Bartlett, G.R., Phosphorus assay in column chromatography, J. Biol. Chem., 1959, vol. 234, pp. 466–468.

    CAS  PubMed  Google Scholar 

  5. Bligh, E.G. and Dyer, W.J., A rapid method of total lipid extraction and purification, Can. J. Biochem. Physiol., 1959, vol. 37, no. 8, pp. 911–917.

    Article  CAS  PubMed  Google Scholar 

  6. Chang, K.T., Anishkin, A., Patwardhan, G.A., et al., Ceramide channels: destabilization by Bcl-xL and role in apoptosis, Biochim. Biophys. Acta, 2015, vol. 1848, no. 10, pp. 2374–2384.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Di Paola, M., Cocco, T., and Lorusso, M., Ceramide interaction with the respiratory chain of heart mitochondria, Biochemistry, 2000, vol. 39, no. 22, pp. 6660–6668.

    Article  PubMed  Google Scholar 

  8. Kaewsuya, P., Danielson, N.D., and Ekhterae, D., Fluorescent determination of cardiolipin using 10-Nnonyl acridine orange, Ann. Bioanal. Chem., 2007, vol. 387, pp. 2775–2782.

    Article  CAS  Google Scholar 

  9. Kornhuber, J., Tripal, P., Reichel, M., et al., Functional inhibitors of acid sphingomyelinase (FIASMAs): a novel pharmacological group of drugs with broad clinical applications, Cell Physiol. Biochem., 2010, vol. 26, pp. 9–20.

    Article  CAS  PubMed  Google Scholar 

  10. Lee, S.-Y., Kim, J.R., Hu, Y., et al., Cardiomyocyte specific deficiency of serine palmitoyltransferase subunit 2 reduces ceramide but leads to cardiac dysfunction, J. Biol. Chem., 2012, vol. 287, no. 22, pp. 18429–18439.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Lowry, O.N., Rosebrough, N.J., Farr, A.L., and Randall, R.J., Protein measurement with the Folin phenol reagent, J. Biol. Chem., 1951, vol. 193, no. 1, pp. 365–375.

    Google Scholar 

  12. Monette, J. S., Gomez, L. A., Moreau, R. F., et al., (R)-α-Lipoic acid treatment restores ceramide balance in aging rat cardiac mitochondria, Pharmacol. Res., 2011, vol. 63, no. 1, pp. 23–29.

    Article  CAS  PubMed  Google Scholar 

  13. Paradies, G., Petrosillo, G., Paradies, V., and Ruggiero, F.M., Oxidative stress, mitochondrial bioenergetics, and cardiolipin in aging, Free Radicals Biol. Med., 2010, vol. 48, pp. 1286–1295.

    Article  CAS  Google Scholar 

  14. Roth, A.G., Drescher, D., Yang, Y., et al., Potent and selective inhibition of acid sphingomyelinase by bisphosphonates, Angew. Chem., Int. Ed. Engl., 2009, vol. 48, pp. 7560–7563.

    Article  CAS  Google Scholar 

  15. Schulz, S., Lichtmannegger, J., Schmitt, S., et al., A protocol for the parallel isolation of intact mitochondria from rat liver, kidney, heart, and brain, Methods Mol. Biol., 2015, vol. 1295, pp. 75–86.

    Article  CAS  PubMed  Google Scholar 

  16. Skrzypiec-Spring, M., Grotthus, B., Szelag, A., and Schulz, R., Isolated heart perfusion according to Langendorff-still viable in the new millennium, J. Pharmacol. Toxicol. Methods, 2007, vol. 55, no. 2, pp. 13–26.

    Article  Google Scholar 

  17. Zachman, D.K., Chicco, A.J., McCune, S.A., et al., The role of calcium-independent phospholipase A2 in cardiolipin remodeling in the spontaneously hypertensive heart failure rat heart, J. Lipid Res., 2010, vol. 51, pp. 525–534.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to N. A. Babenko.

Additional information

Original Russian Text © N.A. Babenko, G.V. Storozhenko, 2017, published in Uspekhi Gerontologii, 2017, Vol. 30, No. 1, pp. 43–48.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Babenko, N.A., Storozhenko, G.V. Role of ceramide in the aging-related decrease of cardiolipin content in the rat heart. Adv Gerontol 7, 195–200 (2017). https://doi.org/10.1134/S207905701703002X

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S207905701703002X

Keywords

Navigation