Effects of rosiglitazone on global ischemia-induced hippocampal injury and expression of mitochondrial uncoupling protein 2.
We investigate the effect of rosiglitazone, a ligand for peroxisome proliferator-activated receptor-gamma (PPARgamma) with anti-inflammatory and anti-oxidative actions, on hippocampal injury and its roles in mitochondrial uncoupling protein 2 (UCP2) expression caused by transient global ischemia (TGI) in rats. Increased UCP2 expression was observed in mitochondria of hippocampal CA1 2-24h after TGI/reperfusion, with maximal expression levels at 6-18h. Administration of rosiglitazone to hippocampus 30min prior to the onset of TGI further enhanced mitochondrial UCP2 expression 2-6h following TGI/reperfusion. Rats subjected to TGI/reperfusion displayed a significant increase in lipid peroxidation, based on increased malondialdehyde (MDA) levels, in hippocampal CA1 mitochondria 2-6 h after reperfusion. Rosiglitazone significantly attenuated TGI/reperfusion-induced lipid peroxidation and suppressed hippocampal CA1 neuronal death based on the surviving neuronal counts. In conclusion, our results provide correlative evidence for the "PPARgamma-->UCP2-->neuroprotection" cascade in ischemic brain injury.
Chen
Shang-Der
SD
Department of Neurology, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Taiwan.
Wu
Hsin-Yi
HY
Yang
Ding-I
DI
Lee
Su-Ying
SY
Shaw
Fu-Zen
FZ
Lin
Tsu-Kung
TK
Liou
Chia-Wei
CW
Chuang
Yao-Chung
YC
D000818:Animals; D006624:Hippocampus / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D007473:Ion Channels / Q000378:metabolism*; D002546:Ischemic Attack, Transient / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D024101:Mitochondrial Proteins / Q000378:metabolism*; D047495:PPAR gamma / Q000037:antagonists & inhibitors*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology*; D000071246:Uncoupling Protein 2
D007473:Ion Channels; D024101:Mitochondrial Proteins; D047495:PPAR gamma; D045162:Thiazolidinediones; C000604391:Ucp2 protein, rat; D000071246:Uncoupling Protein 2; D000077154:Rosiglitazone