Age-induced reduction in mitochondrial manganese superoxide dismutase activity and tolerance of macrophages against apoptosis induced by oxidized low density lipoprotein.

BACKGROUND Oxidative stress is thought to play an important role in age-induced atherogenesis. Manganese superoxide dismutase (MnSOD) is an antioxidant enzyme that is localized in mitochondria and protects macrophages against apoptosis induced by oxidized low density lipoprotein (oxLDL). We previously reported that genetic polymorphism of MnSOD modifies mitochondrial MnSOD (mtMnSOD) activity and increases the risk of coronary artery disease. In this study, we investigated the association of mtMnSOD activity with aging. METHODS AND RESULTS Blood samples were taken from 69 healthy participants aged 20-52. The MnSOD genotype was analyzed using real-time polymerase chain reaction. Leukocyte mtMnSOD activity was measured by inhibition of WST-1. Macrophages were treated with oxLDL and the apoptotic cells were counted. mtMnSOD activity was inversely correlated with the age of the participant regardless of the MnSOD genotype. The percentage of apoptotic macrophages after incubation with oxLDL correlated with age. Thus, the percentage of apoptotic macrophages after incubation with oxLDL was inversely related to mtMnSOD activity. Lecithinized SOD, which can easily transfer into cells, improved the tolerance of macrophages against oxLDL. CONCLUSIONS mtMnSOD activity decreases with age, thereby reducing the tolerance of macrophages against oxLDL-induced apoptosis. Our data may provide an important clue to clarify the mechanisms of age-induced atherosclerosis.