CK2 is a novel negative regulator of NADPH oxidase and a neuroprotectant in mice after cerebral ischemia

Gab Seok Kim, Joo Eun Jung, Kuniyasu Niizuma, Pak H. Chan

研究成果: Article査読

63 被引用数 (Scopus)

抄録

NADPH oxidase is a major complex that produces reactive oxygen species (ROSs) during the ischemic period and aggravates brain damage and cell death after ischemic injury. Although many approaches have been tested for preventing production of ROSs by NADPH oxidase in ischemic brain injury, the regulatory mechanisms of NADPH oxidase activity after cerebral ischemia are still unclear. In this study, we identified casein kinase 2 (CK2) as a critical modulator of NADPH oxidase and elucidated the role of CK2 as a neuroprotectant after oxidative insults to the brain. We found that the protein levels of the catalytic subunits CK2α and CK2α′, as well as the total activity of CK2, are significantly reduced after transient focal cerebral ischemia (tFCI). We also found this deactivation of CK2 caused by ischemia/reperfusion increases expression of Nox2 and translocation of p67 phox and Rac1 to the membrane after tFCI. Interestingly, we found that the inactive status of Rac1 was captured by the catalytic subunit CK2α under normal conditions. However, binding between CK2α and Rac1 was immediately diminished after tFCI, and Rac1 activity was markedly increased after CK2 inhibition. Moreover, we found that deactivation of CK2 in the mouse brain enhances production of ROSs and neuronal cell death via increased NADPH oxidase activity. The increased brain infarct volume caused by CK2 inhibition was restored by apocynin, a NADPH oxidase inhibitor. This study suggests that CK2 can be a direct molecular target for modulation of NADPH oxidase activity after ischemic brain injury.

本文言語English
ページ(範囲)14779-14789
ページ数11
ジャーナルJournal of Neuroscience
29
47
DOI
出版ステータスPublished - 2009 11 25
外部発表はい

ASJC Scopus subject areas

  • Neuroscience(all)

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