Oleate prevents palmitate-induced cytotoxic stress in cardiac myocytes

Thomas A. Miller, Nathan K. LeBrasseur, Gregory M. Cote, Mario P. Trucillo, David R. Pimentel, Yasuo Ido, Neil B. Ruderman, Douglas B. Sawyer

Research output: Contribution to journalArticle

114 Scopus citations

Abstract

The cytotoxicity of saturated fatty acids has been implicated in the pathophysiology of cardiovascular disease, though their effects on cardiac myocytes are incompletely understood. We examined the effects of palmitate and the mono-unsaturated fatty acid oleate on neonatal rat ventricular myocyte cell biology. Palmitate (0.5 mM) increased oxidative stress, as well as activation of the stress-associated protein kinases (SAPK) p38, Erk1/2, and JNK, following 18 h and induced apoptosis in ∼20% of cells after 24 h. Neither antioxidants nor SAPK inhibitors prevented palmitate-induced apoptosis. Low concentrations of oleate (0.1 mM) completely inhibited palmitate-induced oxidative stress, SAPK activation, and apoptosis. Increasing mitochondrial uptake of palmitate with l-carnitine decreased apoptosis, while decreasing uptake with the carnitine palmitoyl transferase-1 inhibitor perhexiline nearly doubled palmitate-induced apoptosis. These results support a model for palmitate-induced apoptosis, activation of SAPKs, and protein oxidative stress in myocytes that involves cytosolic accumulation of saturated fatty acids.

Original languageEnglish (US)
Pages (from-to)309-315
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume336
Issue number1
DOIs
StatePublished - Oct 14 2005

Keywords

  • Apoptosis
  • Cardiomyocyte
  • Lipotoxicity
  • Oleate
  • Oxidative stress
  • Palmitate
  • SAPK

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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  • Cite this

    Miller, T. A., LeBrasseur, N. K., Cote, G. M., Trucillo, M. P., Pimentel, D. R., Ido, Y., Ruderman, N. B., & Sawyer, D. B. (2005). Oleate prevents palmitate-induced cytotoxic stress in cardiac myocytes. Biochemical and Biophysical Research Communications, 336(1), 309-315. https://doi.org/10.1016/j.bbrc.2005.08.088