P1.35 Wednesday, Jan. 4 Effects of Estrogen on Mitochondrial Function in ApoE-deficient Mice FERNANDEZ, W.L.*; ELMUTI, L.F.; KONKLE, M.E.; NATHAN, B.P.; MENZE, M.A.; Eastern Illinois University, Dept. Biol. Sci., Charleston, IL; Eastern Illinois University, Dept. Biol. Sci., Charleston, IL; Eastern Illinois University, Dept. Chem., Charleston, IL; Eastern Illinois University, Dept. Biol. Sci., Charleston, IL; Eastern Illinois University, Dept. Biol. Sci., Charleston, IL email@example.com
ApoE genotype is the major risk factor in a variety of neurological diseases, such as Alzheimer's disease (AD) and Parkinson's disease. Estrogen deficiency is also considered to be a contributing factor in these diseases. One mechanism whereby estrogen can play a role in these diseases is by modulating mitochondrial function. In this study we examined the effects of estrogen on mitochondrial function in apoE-deficient/knockout and wild-type mice. To accomplish this, we measured mitochondrial respiration in purified synaptosomes from the forebrain of 4 - 12 month C57BL/6J mice. Routine respiration of permeabilized synaptosomes in presence of 5 mM pyruvate, 2 mM malate, and 10 mM glutamate at 37 °C was 0.67 ± 0.11 pmol O2•s-1•10-1 mg protein. The fold increase in oxygen flux (respiratory control ratio - RCR) after addition of 2 mM ADP of 9.67 ± 0.48 demonstrated well coupled mitochondria (n = 21, ±SE). The RCR values between synaptosomes isolated from apoE knockout (n = 19) and wild-type mice were similar. Treatment of synaptosomes with 10 µM 4-hydroxynonenal (HNE), a reactive electrophile produced during oxidative stress, lead to a significant drop in the RCR values in both the apoE knockout (5.13 ± 1.26) (n = 11, ±SE) and wild-type mice (4.91 ± 1.75) (n = 5, ±SE). Pre-incubation of synaptosomes with 100 nM estrogen prior to the addition of HNE did not ameliorate these reductions in RCR values. These results suggest that (1) apoE deficiency in mice does not have an effect on mitochondrial RCR and (2) estrogen pre-treatment was unable to rescue oxidative stress induced by HNE. Further studies are needed to explain the role of estrogen and apoE on mitochondria function in neurological disorders (Supported by: CFR-EIU-2011).