Phosphoinositide 3-kinase-gamma expression is upregulated in brain microglia and contributes to ischemia-induced microglial activation in acute experimental stroke

Rong Jin, Shiyong Yu, Zifang Song, Joseph W. Quillin, Daniel P. Deasis, Josef M. Penninger, Anil Nanda, D. Neil Granger, Guohong Li

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Microglia, the resident microphages of the CNS, are rapidly activated after ischemic stroke. Inhibition of microglial activation may protect the brain by attenuating blood-brain barrier damage and neuronal apoptosis after ischemic stroke. However, the mechanisms by which microglia is activated following cerebral ischemia is not well defined. In this study, we investigated the expression of PI3Kγ in normal and ischemic brains and found that PI3Kγ mRNA and protein are constitutively expressed in normal brain microvessels, but significantly upregulated in postischemic brain primarily in activated microglia following cerebral ischemia. In vitro, the expression of PI3Kγ mRNA and protein was verified in mouse brain endothelial and microglial cell lines. Importantly, absence of PI3Kγ blocked the early microglia activation (at 4. h) and subsequent expansion (at 24-72. h) in PI3Kγ knockout mice. The results suggest that PI3Kγ is an ischemia-responsive gene in brain microglia and contributes to ischemia-induced microglial activation and expansion.

Original languageEnglish (US)
Pages (from-to)458-464
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume399
Issue number3
DOIs
StatePublished - Aug 1 2010

Fingerprint

1-Phosphatidylinositol 4-Kinase
Microglia
Phosphatidylinositols
Phosphatidylinositol 3-Kinases
Brain
Phosphotransferases
Ischemia
Chemical activation
Stroke
Brain Ischemia
Messenger RNA
Microvessels
Blood-Brain Barrier
Knockout Mice
Proteins
Endothelial Cells
Genes
Cells
Apoptosis
Cell Line

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Jin, Rong ; Yu, Shiyong ; Song, Zifang ; Quillin, Joseph W. ; Deasis, Daniel P. ; Penninger, Josef M. ; Nanda, Anil ; Granger, D. Neil ; Li, Guohong. / Phosphoinositide 3-kinase-gamma expression is upregulated in brain microglia and contributes to ischemia-induced microglial activation in acute experimental stroke. In: Biochemical and Biophysical Research Communications. 2010 ; Vol. 399, No. 3. pp. 458-464.
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Phosphoinositide 3-kinase-gamma expression is upregulated in brain microglia and contributes to ischemia-induced microglial activation in acute experimental stroke. / Jin, Rong; Yu, Shiyong; Song, Zifang; Quillin, Joseph W.; Deasis, Daniel P.; Penninger, Josef M.; Nanda, Anil; Granger, D. Neil; Li, Guohong.

In: Biochemical and Biophysical Research Communications, Vol. 399, No. 3, 01.08.2010, p. 458-464.

Research output: Contribution to journalArticle

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