Oleate prevents palmitate-induced cytotoxic stress in cardiac myocytes.
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 (0.5mM) increased oxidative stress, as well as activation of the stress-associated protein kinases (SAPK) p38, Erk1/2, and JNK, following 18h and induced apoptosis in approximately 20% of cells after 24h. Neither antioxidants nor SAPK inhibitors prevented palmitate-induced apoptosis. Low concentrations of oleate (0.1mM) 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.
Miller
Thomas A
TA
Molecular Stress Response Unit, Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, MA 02118, USA.
LeBrasseur
Nathan K
NK
Cote
Gregory M
GM
Trucillo
Mario P
MP
Pimentel
David R
DR
Ido
Yasuo
Y
Ruderman
Neil B
NB
Sawyer
Douglas B
DB
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D066298:In Vitro Techniques; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000201:enzymology; D019301:Oleic Acid / Q000494:pharmacology*; D018384:Oxidative Stress; D019308:Palmitic Acid / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D051381:Rats
D019301:Oleic Acid; D019308:Palmitic Acid; D020928:Mitogen-Activated Protein Kinases