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Age‐Dependent Decreases in Mitochondrial Respiration are Exacerbated by Calcium in Female Rat Hearts
Author(s) -
Hunter James Craig,
Machikas Alexandra M,
Korzick Donna H
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.1097.6
Subject(s) - mitochondrion , endocrinology , antimycin a , medicine , respiration , calcium , rotenone , menopause , ischemia , estrogen , biology , chemistry , biochemistry , anatomy
Background Cardiovascular disease mortality increases rapidly following menopause by poorly defined mechanisms. Since mitochondrial Ca 2+ overload has been identified as a trigger of cell death following myocardial ischemia, we sought to determine if aging and/or estrogen deficiency (OVX) increased mitochondrial Ca 2+ sensitivity. Methods Respiration (MR) was measured in ventricular mitochondria isolated from adult (6mo; n=9) and aged (24mo; n=11), intact or OVX female rats using the substrates: Oxoglutarate/Malate (Complex I); Succinate/Rotenone (Complex II); Ascorbate/TMPD/Antimycin (Complex IV). State 2 and State 3 MR was initiated by sequential addition of mitochondria and ADP. Ca 2+ sensitivity was assessed by the reduction in respiratory control index (RCI; state 3/state 2) with 0.5mM Ca 2+ . Results In the absence of Ca 2+ , adult female RCIs for complexes I and II were 10.3 and 2.1, respectively. Although there was no effect of age on complex IV MR, aging decreased the RCI's for complexes I and II by 14% and 8%, respectively, independent of ovary status (p<0.05). Interestingly, Ca 2+ reduced complex I RCI by 32% (p<0.05) in aged but not adult rat hearts demonstrating an age‐dependent decrease in Ca 2+ tolerance. Conclusions That aged female mitochondria are more sensitive to Ca 2+ may explain in part the age‐associated decreases in female ischemic tolerance. This work was supported by NHLBI RO1 HL091097