Suppression of Etk/Bmx protects against ischemic brain injury

Kai Yun Chen, John Chung Che Wu, Cheng Fu Chang, Yuan Hao Chen, Wen Ta Chiu, Ya Hsin Lou, Yen Hua Chen, Hsiu Ming Shih, Yung Hsiao Chiang

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)

Abstract

Etk/Bmx (epithelial and endothelial tyrosine kinase, also known as BMX), a member of the Tec (tyrosine kinase expressed in hepatocellular carcinoma) family of protein-tyrosine kinases, is an important regulator of signal transduction for the activation of cell growth, differentiation, and development. We have previously reported that activation of Etk leads to apoptosis in MDA-MB-468 cells. The purpose of this study was to examine the role of Etk in neuronal injury induced by H 2O 2 or ischemia. Using Western blot analysis and immunohistochemistry, we found that treatment with H 2O 2 significantly enhanced phosphorylation of Etk and its downstream signaling molecule Stat1 in primary cortical neurons. Inhibiting Etk activity by LFMA13 or knocking down Etk expression by a specific shRNA increased the survival of primary cortical neurons. Similarly, at 1 day after a 60-min middle cerebral artery occlusion (MCAo) in adult rats, both phosphorylated Etk and Stat1 were coexpressed with apoptotic markers in neurons in the penumbra. Pretreatment with LFM-A13 or an adenoviral vector encoding the kinase deletion mutant EtkΔk attenuated caspase- 3 activity and infarct volume in ischemic brain. All together, our data suggest that Etk is activated after neuronal injury. Suppressing Etk activity protects against neurodegeneration in ischemic brain.

Original languageEnglish
Pages (from-to)345-354
Number of pages10
JournalCell Transplantation
Volume21
Issue number1
DOIs
Publication statusPublished - 2012

Keywords

  • Apoptosis
  • Cerebral ischemia
  • Etk/bmx
  • Stat1

ASJC Scopus subject areas

  • Cell Biology
  • Transplantation
  • Biomedical Engineering

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