This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Huang, C.-Y. Articles by Chan, P. H. Search for Related Content PubMed PubMed Citation Articles by Huang, C.-Y. Articles by Chan, P. H. Related Collections Oxidant stress Cell signalling/signal transduction Gene expression Ischemic biology - basic studies

(Stroke. 2001;32:741.)
© 2001 American Heart Association, Inc.

Original Contributions

Overexpression of Copper-Zinc Superoxide Dismutase Attenuates Acute Activation of Activator Protein-1 After Transient Focal Cerebral Ischemia in Mice

Chiung-Ying Huang, PhD; Miki Fujimura, MD; Yung-Yee Chang, PhD Pak H. Chan, PhD

From the Department of Neurosurgery, Department of Neurology and Neurological Sciences, and Program in Neurosciences, Stanford University School of Medicine (Calif).

Correspondence to Pak H. Chan, PhD, Stanford University, MSLS, 1201 Welch Rd, #P304, Stanford, CA 94305-5487. E-mail phchan{at}leland.stanford.edu

Background and Purpose—Reactive oxygen species (ROS) have been implicated in reperfusion injury after focal cerebral ischemia (FCI). ROS are known to regulate the activity of transcription factors such as activator protein-1 (AP-1), which is a dimer consisting of members of the Jun and Fos families. We investigated the role of ROS in AP-1 activity after FCI using transgenic mice that overexpressed copper-zinc superoxide dismutase (SOD1) and that had reduced infarction volume after FCI.

Methods—The SOD1 transgenic mice and their wild-type littermates were subjected to middle cerebral artery occlusion and reperfusion by intraluminal suture blockade. After 60 minutes of middle cerebral artery occlusion, mice were allowed to recover for 1, 2, and 4 hours before euthanasia. Protein expression of c-Jun and c-Fos was examined by immunohistochemistry and Western blotting. AP-1 DNA-protein binding activity was assessed by electrophoretic mobility shift assays.

Results—In wild-type mice, immunohistochemistry demonstrated acute c-Jun and c-Fos activation in ischemic cortex and its outer boundary. Expression of both was reduced in SOD1 transgenic mice. Western blotting confirmed that SOD1 overexpression was associated with reduced c-Jun and c-Fos protein levels in ischemic brain. Electrophoretic mobility shift assays revealed that the ischemia-enhanced DNA binding activity observed in wild-type mice was reduced in SOD1 transgenic mice. Supershift assays indicated that c-Jun participated in the bound AP-1 complex.

Conclusions—SOD1 overexpression prevents early activation of AP-1 after transient FCI in mice. This may block the expression of downstream target genes that are injurious, thereby reducing the infarction volume after transient FCI in mice.

Key Words: cerebral ischemia, focal • free radicals • superoxide dismutase • transcription factor AP-1 • transcription factors • mice

This article has been cited by other articles:

				C. H. Liu, S. Huang, J. Cui, Y. R. Kim, C. T. Farrar, M. A. Moskowitz, B. R. Rosen, and P. K. Liu MR contrast probes that trace gene transcripts for cerebral ischemia in live animals FASEB J, September 1, 2007; 21(11): 3004 - 3015. [Abstract] [Full Text] [PDF]

				N. Noshita, T. Sugawara, A. Lewen, T. Hayashi, and P. H. Chan Copper-Zinc Superoxide Dismutase Affects Akt Activation After Transient Focal Cerebral Ischemia in Mice Stroke, June 1, 2003; 34(6): 1513 - 1518. [Abstract] [Full Text] [PDF]

				N. Ishibashi, O. Prokopenko, K. R. Reuhl, and O. Mirochnitchenko Inflammatory Response and Glutathione Peroxidase in a Model of Stroke J. Immunol., February 15, 2002; 168(4): 1926 - 1933. [Abstract] [Full Text] [PDF]