Alpha linolenic acid decreases apoptosis and oxidized phospholipids in cardiomyocytes during ischemia/reperfusion
| Autor: | Rakesh Chaudhary, Devin Hasanally, Aleksandra Stamenkovic, Amir Ravandi, Grant N. Pierce, Riya Ganguly, Thane G. Maddaford |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Programmed cell death Clinical Biochemistry Ischemia Apoptosis Myocardial Reperfusion Injury 030204 cardiovascular system & hematology Pharmacology Biology Rats Sprague-Dawley 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Phosphatidylcholine medicine Animals Myocytes Cardiac cardiovascular diseases Viability assay Molecular Biology Phospholipids chemistry.chemical_classification alpha-Linolenic acid alpha-Linolenic Acid Fatty acid Cell Biology General Medicine medicine.disease Rats 030104 developmental biology Biochemistry chemistry DNA fragmentation Oxidation-Reduction |
| Zdroj: | Molecular and Cellular Biochemistry. 437:163-175 |
| ISSN: | 1573-4919 0300-8177 |
| Popis: | The omega-3 fatty acid, alpha linolenic acid (ALA) found in plant-derived foods induces significant cardiovascular benefits when ingested. ALA may be cardioprotective during ischemia; however, the mechanism(s) responsible for this effect is unknown. Isolated adult rat cardiomyocytes were exposed to medium containing ALA for 24 h and then exposed to non-ischemic (control), simulated ischemia (ISCH), or simulated ischemia/reperfusion (IR) conditions. Cardiomyocyte phospholipids were extracted and analyzed by an HPLC/electrospray ionization tandem mass spectrometry system. Pre-treatment of cells with ALA resulted in a significant incorporation of ALA within cardiomyocyte phosphatidylcholine. Cell death, DNA fragmentation and caspase-3 activity increased during ischemia and ischemia/reperfusion. Two pro-apoptotic oxidized phosphatidylcholine (OxPC) species, 1-palmitoyl-2-(5′-oxo-valeroyl)-sn-glycero-3-phosphocholine (POVPC), and 1-palmitoyl-2-glutaroyl-sn-glycero-3-phosphocholine (PGPC) were significantly increased during both ischemia and ischemia/reperfusion. Pre-treatment of the cells with ALA resulted in a significant reduction in cell death during ischemia and ischemia/reperfusion challenge. Apoptosis was also inhibited during ischemia and ischemia/reperfusion as shown by reduced DNA fragmentation and decreased caspase activation. ALA pre-treatment significantly decreased the production of POVPC and PGPC during ischemia and ischemia/reperfusion. ALA pre-treatment also significantly increased in resting Ca2+ during ischemia or ischemia/reperfusion but did not improve Ca2+ transients. ALA protects the cardiomyocyte from apoptotic cell death during simulated ISCH and IR by inhibiting the production of specific pro-apoptotic OxPC species. OxPCs represent a viable interventional target to protect the heart during ischemic challenge. |
| Databáze: | OpenAIRE |
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