Enhancement of mitochondrial oxidative stress and up-regulation of antioxidant protein peroxiredoxin III/SP-22 in the mitochondria of human pre-eclamptic placentae.
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.
Shibata
E
E
Department of Obstetrics and Gynecology, University of Occupational and Environmental Health, 807-8555, Kitakyushu, Japan. age-s@d8.dion.ne.jp
Nanri
H
H
Ejima
K
K
Araki
M
M
Fukuda
J
J
Yoshimura
K
K
Toki
N
N
Ikeda
M
M
Kashimura
M
M
D000328:Adult; D000447:Aldehydes / Q000378:metabolism; D005260:Female; D005865:Gestational Age; D006801:Humans; D007124:Immunoenzyme Techniques; D015227:Lipid Peroxidation; D008928:Mitochondria / Q000378:metabolism*; D018384:Oxidative Stress; D010544:Peroxidases / Q000235:genetics / Q000378:metabolism*; D061105:Peroxiredoxin III; D054464:Peroxiredoxins; D010920:Placenta / Q000378:metabolism* / Q000473:pathology; D011225:Pre-Eclampsia / Q000378:metabolism* / Q000473:pathology; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation
D000447:Aldehydes; D012333:RNA, Messenger; D010544:Peroxidases; C516115:PRDX3 protein, human; D061105:Peroxiredoxin III; D054464:Peroxiredoxins; C027576:4-hydroxy-2-nonenal