Phosphoinositide 3-kinase-gamma expression is upregulated in brain microglia and contributes to ischemia-induced microglial activation in acute experimental stroke.
Phosphoinositide 3-kinase-gamma expression is upregulated in brain microglia and contributes to ischemia-induced microglial activation in acute experimental stroke.
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DOI：
10.1016/j.bbrc.2010.07.116
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发表时间：
2010-08-27
影响因子：
3.1
通讯作者：
Li, Guohong
中科院分区：
文献类型：
--
作者：
Jin, Rong;Yu, Shiyong;Song, Zifang;Quillin, Joseph W.;Deasis, Daniel P.;Penninger, Josef M.;Nanda, Anil;Granger, D. Neil;Li, Guohong
小胶质细胞是中枢神经系统的常驻微噬细胞，在缺血性中风后迅速激活。抑制小胶质细胞的激活可能通过减轻缺血性脑卒中后的血脑屏障损伤和神经元凋亡来保护大脑。然而，脑缺血后小胶质细胞被激活的机制尚不清楚。在本研究中，我们研究了PI3Kgamma在正常脑和缺血脑中的表达，发现PI3Kgamma mRNA和蛋白在正常脑微血管中组成性表达，但在脑缺血后的脑缺血后，PI3Kgamma mRNA和蛋白主要在激活的小胶质细胞中显著上调。体外实验验证了PI3Kgamma mRNA和蛋白在小鼠脑内皮细胞和小胶质细胞中的表达。重要的是，PI3Kgamma缺失阻断了PI3Kγ敲除小鼠的早期小胶质细胞激活（4h）和随后的扩张（24-72 h）。结果表明，PI3Kγ是脑小胶质细胞的缺血反应基因，参与缺血诱导的小胶质细胞激活和扩增。
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 present study we investigated the expression of PI3Kgamma in normal and ischemic brains and found that PI3Kgamma 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 PI3Kgamma mRNA and protein was verified in mouse brain endothelial and microglial cell lines. Importantly, absence of PI3Kgamma blocked the early microglia activation (at 4h) 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.
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影响因子：
82.9
作者：
Barber, DF;Bartolomé, A;Carrera, AC
通讯作者：
Carrera, AC
影响因子：
6.3
作者：
Denes, Adam;Vidyasagar, Rishma;Allan, Stuart M.
通讯作者：
Allan, Stuart M.
影响因子：
20.3
作者：
Puri, KD;Doggett, TA;Diacovo, TG
通讯作者：
Diacovo, TG
影响因子：
8.3
作者：
Terao S;Yilmaz G;Stokes KY;Russell J;Ishikawa M;Kawase T;Granger DN
通讯作者：
Granger DN
影响因子：
5.3
作者：
Schilling, M;Besselmann, M;Kiefer, R
通讯作者：
Kiefer, R