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Dietary Supplementation with Docosahexanoic Acid or Arachidonic Acid Delay Ca2+ ‐Induced Permeability Transition Pore Opening in Cardiac Mitochondria
Author(s) -
Khairallah Ramzi J,
O'Shea Karen M,
Galvao Tatiana,
O'Connell Kelly,
Polster Brian M,
Rosiers Christine Des,
Stanley William C
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.1097.4
Subject(s) - mptp , mitochondrial permeability transition pore , arachidonic acid , docosahexaenoic acid , chemistry , endocrinology , medicine , phospholipid , polyunsaturated fatty acid , mitochondrion , carnitine , fish oil , fatty acid , biochemistry , biology , apoptosis , dopaminergic , programmed cell death , membrane , fishery , fish <actinopterygii> , dopamine , enzyme
Supplementation with docosahexanoic acid (DHA, commonly found in fish oil) in clinically relevant amounts causes a 2‐fold increase in DHA in cardiac phospholipids, and delays Ca 2+ ‐induced mitochondrial permeability transition pore (MPTP) opening. The mechanism for this effect is not clear, however the increase in DHA is accompanied by a decrease in the ù‐6 PUFA arachidonic acid (ARA), which could be responsible for the effects on the MPTP. We determined the role of ARA on MPTP opening by feeding rats DHA, ARA or DHA+ARA. Male Wistar rats were fed either a los DHA+AHA diet(CTRL), a diet containing DHA or ARA at 2.5% of energy intake, or both DHA and ARA at 2.5% each, for 10 wks. Cardiac mitochondria were isolated. All three diets profoundly altered the phospholipid composition of mitochondria compared to CTRL. Both the DHA and ARA groups delayed Ca 2+ ‐induced MPTP opening vs. CTRL (p<0.05) while DHA+ARA increased sensitivity to MPTP opening (p<0.05 vs CTRL, DHA or ARA). Furthermore, both diets containing ARA significantly increased the pro‐inflammatory marker TBX B2 by 2‐ to 3‐fold compared to CTRL and DHA diets (p<0.05). DHA+ARA also increased lipid peroxidation compared to ARA alone (p=0.008) and to CTRL (p=0.034). This suggests that the effect of DHA on MPTP is not due to depletion of ARA. DHA+ARA showed no added benefit, but rather sensitized MPTP to opening, suggesting that a very large dose of PUFA might be detrimental.