Free fatty acids act as endogenous ionophores, resulting in Na+ and Ca2+ influx and myocyte apoptosis
| Autor: | Ming-Jai Su, Mei-Lin Wu, Chung-Liang Chien, Chien-Liang Lin, An-Sheng Lee, Kwang-Ming Fang |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
Male
Patch-Clamp Techniques Time Factors Physiology Linoleic acid Guinea Pigs Palmitic Acid Apoptosis Fatty Acids Nonesterified In Vitro Techniques Mitochondrion Biology Mitochondrial Membrane Transport Proteins Mitochondria Heart Membrane Potentials Linoleic Acid chemistry.chemical_compound Cytosol Physiology (medical) Animals Myocytes Cardiac Inner mitochondrial membrane Heart metabolism Arachidonic Acid Microscopy Confocal Ionophores Caspase 3 Mitochondrial Permeability Transition Pore Sodium Cytochromes c Molecular biology Microscopy Electron Animals Newborn Biochemistry chemistry Calcium Female lipids (amino acids peptides and proteins) Arachidonic acid Mitochondrial Swelling Cardiology and Cardiovascular Medicine Intracellular Oleic Acid |
| Zdroj: | Cardiovascular Research. 78:533-545 |
| ISSN: | 1755-3245 0008-6363 |
| DOI: | 10.1093/cvr/cvn030 |
| Popis: | Disturbances in lipid metabolism have been suggested to play an important role in myocardial damage. Marked accumulation of free fatty acids (FFAs), including arachidonic acid (AA), palmitic acid, oleic acid, and linoleic acid, occurs during post-ischaemia and reperfusion (post-I/R). Possible cellular mechanisms of AA/FFAs-induced myocyte apoptosis were investigated.In neonatal rat ventricular myocytes, AA/FFAs activate a novel non-selective cation conductance (NSCC), resulting in both intracellular Ca(2+) and Na(+) overload. AA caused sustained cytosolic [Na(+)](cyt) and [Ca(2+)](cyt) overload, resulting in mitochondrial [Na(+)](m) and [Ca(2+)](m) overload, which induced caspase-3-mediated apoptosis. Similar apoptotic effects were seen using Na(+) ionophore cocktail/Ca(2+)-free medium, which induced [Na(+)](cyt) and [Na(+)](m), but not [Ca(2+)](cyt) and [Ca(2+)](m) overload. Electron microscopy showed that inhibition of [Na(+)](m) overload prevented disruption of the mitochondrial membrane, showing that [Na(+)](m) overload is an important upstream signal in AA- and FFA-induced myocyte apoptosis.AA and FFAs, which accumulate in the myocardium during post-I/R, may therefore act as naturally occurring endogenous ionophores and contribute to the myocyte death seen during post-I/R. |
| Databáze: | OpenAIRE |
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