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(Stroke. 2004;35:2560.)
© 2004 American Heart Association, Inc.

Original Contributions

Oxidative Stress Affects the Integrin-Linked Kinase Signaling Pathway After Transient Focal Cerebral Ischemia

Atsushi Saito, MD; Takeshi Hayashi, MD PhD; Shuzo Okuno, MD; Tatsuro Nishi, MD PhD Pak H. Chan, PhD

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

Correspondence to Dr Pak H. Chan, Neurosurgical Laboratories, Stanford University, 1201 Welch Rd, MSLS #P314, Stanford, CA 94305-5487. E-mail phchan{at}stanford.edu

Background and Purpose— The integrin-linked kinase (ILK) signaling pathway contributes to regulation of cellular adhesion, migration, and differentiation, and to apoptotic cell death after a variety of cell death stimuli. We have reported that overexpression of copper/zinc superoxide dismutase (SOD1) reduces apoptotic cell death by promoting the phosphatidylinositol 3-kinase (PI3-K)/Akt survival pathway after transient focal cerebral ischemia (tFCI). However, the role of the ILK pathway after tFCI and the role of oxygen free radicals in regulation of apoptosis remain unclear.

Methods— To clarify these issues, we used an in vivo tFCI model with SOD1 transgenic mice and wild-type mice. We administered the PI3-K inhibitor, LY294002, into mouse brains after tFCI and examined the role of PI3-K in the ILK pathway and expression of the ILK/Akt complex by immunohistochemistry, Western blot analysis, and coimmunoprecipitation.

Results— A transient increase in ILK was detected early after tFCI and was prevented by treatment with LY294002, but promoted by SOD1. Coimmunoprecipitation revealed that the direct reaction of ILK/Akt transiently increased concurrent with the increase in ILK after tFCI. Moreover, the ILK/Akt complex was prevented by LY294002, but promoted by SOD1.

Conclusions— These results suggest that the ILK pathway mediated by PI3-K is affected by tFCI and by SOD1.

Key Words: apoptosis • cerebral ischemia • superoxide dismutase