Enhancement of Mitochondrial Oxidative Stress and Up-regulation of Antioxidant Protein Peroxiredoxin III/SP-22 in the Mitochondria of Human Pre-eclamptic Placentae

Abstract

A growing body of evidence indicates that the pathogenesis of pre-eclampsia is closely associated with oxidative stress occurring in mitochondria. In the present study, we evaluated the degree of mitochondrial lipid peroxidation by assessing the accumulation of 4-hydroxy-2-nonenal (HNE)-modified proteins and examined the expression of mitochondrial antioxidant protein peroxiredoxin III/SP-22 in normal and pre-eclamptic human placentae. The accumulation of HNE-modified proteins increased to a greater extent in both the mitochondria and cytosol of pre-eclamptic placentae than in those of normal placentae. Moreover, the accumulation of HNE-modified proteins was much more evident in the mitochondria than in the cytosol, indicating that lipid peroxidation occurred mainly in the mitochondria of pre-eclamptic placentae. The mRNA expression of peroxiredoxin III/SP-22 was increased about 2-fold in pre-eclamptic placentae compared to normal placentae. The protein levels of peroxiredoxin III/SP-22 were approximately 4-fold higher in pre-eclamptic placentae than in normal placentae. Immunohistochemistry of placental tissues showed that the levels of peroxiredoxin III/SP-22 protein were increased in the trophoblasts of floating villi, stromal cells of stem villi, and decidual cells in pre-eclamptic placentae. These results indicate that peroxiredoxin III/SP-22 plays a crucial role in the protection of placental function from oxidative stress occurring in mitochondria of pre-eclamptic placentae.