Caloric restriction and gender modulate cardiac muscle mitochondrial H2O2 production and oxidative damage.
OBJECTIVE
Gender and diet have an important effect in cardiovascular disease and other aging-associated disorders, whose initiation and/or worsening seem to be delayed in females from different species and in animals subjected to caloric restriction (CR). The aim of the present study was to investigate whether cardiac muscle bioenergetic mitochondrial features could be responsible for these beneficial effects.


METHODS
Fifteen-month-old male and female Wistar rats were fed ad libitum or subjected to 40% CR for 3 months. Cardiac mitochondrial function (citrate synthase activity, oxygen consumption), activity of complexes I, III, IV and ATPase of the OXPHOS system, antioxidant activities (MnSOD, GPx), mitochondrial DNA and protein content, mitochondrial H2O2 production, heart oxidative damage, complex IV and ATPase content and efficiency, as well as protein levels of mitochondrial transcription factor A (TFAM) and peroxisome-proliferator-activated receptor-gamma co-activator 1 alpha (PGC1alpha) were measured.


RESULTS
Female and CR rats exhibited lower cardiac mitochondria content, which were more efficient and generated less H2O2 than in males and ad libitum fed animals, with their consequent lower heart oxidative damage.


CONCLUSIONS
Higher mitochondrial differentiation becomes a metabolic adaptation to increase energy efficiency, as what happens in female and CR rats. This adaptation is associated with their lower mitochondrial free radical production and oxidative damage, which could help to understand the mechanism by which these animals exhibit a lower incidence of aging-related disorders, including cardiovascular disease.
Colom
Bartomeu
B
Departament de Biologia Fonamental i Ciències de la Salut, Grup de Metabolisme Energètic i Nutrició, Institut Universitari d'Investigació en Ciències de la Salut (IUNICS), Universitat de les Illes Balears, Palma de Mallorca, Spain.
Oliver
Jordi
J
Roca
Pilar
P
Garcia-Palmer
Francisco J
FJ
D000251:Adenosine Triphosphatases / Q000032:analysis / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D031204:Caloric Restriction; D002950:Citrate (si)-Synthase / Q000378:metabolism; D004272:DNA, Mitochondrial / Q000032:analysis; D004268:DNA-Binding Proteins / Q000032:analysis / Q000378:metabolism; D003576:Electron Transport Complex IV / Q000032:analysis / Q000378:metabolism; D005260:Female; D006861:Hydrogen Peroxide / Q000378:metabolism*; D008297:Male; D008929:Mitochondria, Heart / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000032:analysis / Q000378:metabolism; D016877:Oxidants / Q000378:metabolism*; D010085:Oxidative Phosphorylation; D018384:Oxidative Stress; D010101:Oxygen Consumption; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D016601:RNA-Binding Proteins; D051381:Rats; D017208:Rats, Wistar; D012723:Sex; D014157:Transcription Factors / Q000032:analysis / Q000378:metabolism
D004272:DNA, Mitochondrial; D004268:DNA-Binding Proteins; D024101:Mitochondrial Proteins; D016877:Oxidants; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C501429:Ppargc1a protein, rat; D016601:RNA-Binding Proteins; D014157:Transcription Factors; C422562:mitochondrial transcription factor A; D006861:Hydrogen Peroxide; D003576:Electron Transport Complex IV; D002950:Citrate (si)-Synthase; D000251:Adenosine Triphosphatases