Overexpression of thioredoxin in transgenic mice attenuates focal ischemic brain damage.
Thioredoxin (TRX) plays important biological roles both in intra- and extracellular compartments, including in regulation of various intracellular molecules via thiol redox control. We produced TRX overexpressing mice and confirmed that there were no anatomical and physiological differences between wild-type (WT) mice and TRX transgenic (Tg) mice. In the present study we subjected mice to focal brain ischemia to shed light on the role of TRX in brain ischemic injury. At 24 hr after middle cerebral artery occlusion, infarct areas and volume were significantly smaller in Tg mice than in WT mice. Moreover neurological deficit was ameliorated in Tg mice compared with WT mice. Protein carbonyl content, a marker of cellular protein oxidation, in Tg mice showed less increase than did that of WT mice after the ischemic insult. Furthermore, c-fos expression in Tg mice was stronger than in WT mice 1 hr after ischemia. Our results suggest that transgene expression of TRX decreased ischemic neuronal injury and that TRX and the redox state modified by TRX play a crucial role in brain damage during stroke.
Takagi
Y
Y
Department of Neurosurgery, Graduate School of Medicine, Kyoto University, Kyoto, 606-8507 Japan.
Mitsui
A
A
Nishiyama
A
A
Nozaki
K
K
Sono
H
H
Gon
Y
Y
Hashimoto
N
N
Yodoi
J
J
D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001921:Brain / Q000098:blood supply / Q000473:pathology / Q000503:physiopathology; D002544:Cerebral Infarction / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D002560:Cerebrovascular Circulation; D005786:Gene Expression Regulation; D005979:Glutathione Peroxidase / Q000235:genetics; D006801:Humans; D002546:Ischemic Attack, Transient / Q000235:genetics / Q000473:pathology* / Q000517:prevention & control; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D013482:Superoxide Dismutase / Q000235:genetics; D013879:Thioredoxins / Q000378:metabolism*
D000975:Antioxidants; D019253:Proto-Oncogene Proteins c-bcl-2; D013879:Thioredoxins; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase