Changes in the expression of mitochondrial peroxiredoxin and thioredoxin in neurons and glia and their protective effects in experimental cerebral ischemic damage.
We observed chronological changes in the mitochondrial-specific antioxidant enzymes peroxiredoxin 3 (Prx3) and thioredoxin 2 (Trx2) and their neuroprotective effects in the hippocampal CA1 region after 5 min of transient cerebral ischemia in gerbils. In the sham-operated group, weak Prx3 and Trx2 immunoreactivity was detected in the stratum pyramidale. Prx3 immunoreactivity was increased in pyramidal neurons and expressed in microglia 1 and 3 days, respectively, after ischemia/reperfusion (I/R). Trx2 immunoreactivity in pyramidal neurons increased 30 min and 1 day after I/R and decreased 6 h after I/R. Trx2 immunoreaction was expressed in astrocytes at 3 days postischemia. The intraventricular administration of Prx3 or Prx3/Trx2 (16 microg/20 microl, icv) using an osmotic pump significantly reduced ischemia-induced hyperactivity in a spontaneous motor test and protected CA1 pyramidal neurons from the ischemic damage. In addition, the activation of astrocytes and microglia was decreased in the ischemic CA1 region after Prx3/Trx2 treatment. In addition, treatment with Prx3 or Prx3/Trx2 significantly reduced lipid peroxidation and the release of cytochrome c from mitochondria and cytoplasm in the ischemic CA1 region. These results suggest that changes in the expression of Prx3 and Trx2 in the hippocampal CA1 region after I/R may be associated with the delayed neuronal death of CA1 pyramidal cells induced by transient cerebral ischemia, and that treatment with Prx3 or Prx3/Trx2 in ischemic brains shows a potent neuroprotective effect against ischemic damage by reducing lipid peroxidation and mitochondrial-mediated apoptosis by I/R.
Hwang
In Koo
IK
Department of Anatomy and Cell Biology, College of Veterinary Medicine, and BK21 Program for Veterinary Science, Seoul National University, Seoul 151-742, South Korea.
Yoo
Ki-Yeon
KY
Kim
Dae Won
DW
Lee
Choong Hyun
CH
Choi
Jung Hoon
JH
Kwon
Young-Guen
YG
Kim
Young-Myeong
YM
Choi
Soo Young
SY
Won
Moo-Ho
MH
D000818:Animals; D015153:Blotting, Western; D056547:CA1 Region, Hippocampal / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D005455:Fluorescent Antibody Technique; D015870:Gene Expression; D005849:Gerbillinae; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D002546:Ischemic Attack, Transient / Q000378:metabolism* / Q000473:pathology; D015227:Lipid Peroxidation / Q000502:physiology; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D054464:Peroxiredoxins / Q000378:metabolism* / Q000494:pharmacology; D017966:Pyramidal Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D013879:Thioredoxins / Q000378:metabolism* / Q000494:pharmacology
D013879:Thioredoxins; D054464:Peroxiredoxins