Oxidative stress increases phosphorylation of I kappa B kinase-alpha by enhancing NF-kappa B-inducing kinase after transient focal cerebral ischemia
- Authors
- Song, Yun Seon; Kim, Min-Soo; Kim, Hyun-Ae; Jung, Bo-In; Yang, Jiwon; Narasimhan, Purnima; Kim, Gab Seok; Jung, Joo Eun; Park, Eun-Hee; Chan, Pak H.
- Issue Date
- Jul-2010
- Publisher
- NATURE PUBLISHING GROUP
- Keywords
- focal cerebral ischemia; histone H3 phosphorylation; I kappa B kinase-alpha; NF-kappa B-inducing kinase; oxidative stress; oxygen-glucose deprivation
- Citation
- JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, v.30, no.7, pp 1265 - 1274
- Pages
- 10
- Journal Title
- JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
- Volume
- 30
- Number
- 7
- Start Page
- 1265
- End Page
- 1274
- URI
- https://scholarworks.sookmyung.ac.kr/handle/2020.sw.sookmyung/13181
- DOI
- 10.1038/jcbfm.2010.6
- ISSN
- 0271-678X
1559-7016
- Abstract
- The I kappa B kinase (IKK) complex is a central component in the classic activation of the nuclear factor-kappa B (NF-kappa B) pathway. It has been reported to function in physiologic responses, including cell death and inflammation. We have shown that IKK is regulated by oxidative status after transient focal cerebral ischemia (tFCI) in mice. However, the mechanism by which oxidative stress influences IKKs after tFCI is largely unknown. Nuclear accumulation and phosphorylation of IKK alpha (pIKK alpha) were observed 1 h after 30 mins of tFCI in mice. In copper/zinc-superoxide dismutase knockout mice, levels of NF-kappa B-inducing kinase (NIK) (an upstream kinase of IKK alpha), pIKK alpha, and phosphorylation of histone H3 (pH3) on Ser10 were increased after tFCI and were higher than in wild-type mice. Immunohistochemistry showed nuclear accumulation and pIKK alpha in mouse brain endothelial cells after tFCI. Nuclear factor-kappa B-inducing kinase was increased, and it enhanced pH3 by inducing pIKK alpha after oxygen-glucose deprivation (OGD) in mouse brain endothelial cells. Both NIK and pH3 interactions with IKK alpha were confirmed by coimmunoprecipitation. Treatment with IKK alpha small interfering RNA significantly reduced cell death after OGD. These results suggest that augmentation of NIK, IKK alpha, and pH3 in response to oxidative stress is involved in cell death after cerebral ischemia (or stroke). Journal of Cerebral Blood Flow & Metabolism (2010) 30, 1265-1274; doi:10.1038/jcbfm.2010.6; published online 3 February 2010
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