Paxillin and hydrogen peroxide-inducible clone 5 expression and distribution in control and Alzheimer disease hippocampi.
Paxillin and hydrogen peroxide-inducible clone 5 expression and distribution in control and Alzheimer disease hippocampi.
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DOI:
10.1097/nen.0b013e3181d53d98
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发表时间:
2010-04
影响因子:
3.2
通讯作者:
Bowser R
中科院分区:
文献类型:
--
作者:
Caltagarone J;Hamilton RL;Murdoch G;Jing Z;DeFranco DB;Bowser R
Hydrogen peroxide-inducible-clone 5 (Hic-5) and paxillin are members of the group III LIM domain protein family that localize to both cell nuclei and focal adhesions and link integrin-mediated signaling to the actin cytoskeleton. Prior in vitro studies have implicated paxillin in β-amyloid-induced cell death but little is known about the expression and function of Hic-5 and paxillin in the brain. We performed a blinded retrospective cross-sectional study of Hic-5 and paxillin expression in the hippocampus of Alzheimer disease (AD) and control subjects using immunohistochemistry and laser scanning confocal microscopy. The analysis included assessment of the expression of phosphorylated isoforms of paxillin that reflect activation of distinct signaling pathways. We found changes in the subcellular distribution of Hic-5, paxillin and specific phosphorylated isoforms of paxillin in the AD brains. Hic-5 and phosphorylated isoforms of paxillin colocalized with neurofibrillary tangles. Paxillin was predominantly found in reactive astrocytes in the AD hippocampi and activated paxillin was also detected in granulovacuolar bodies in AD. These data indicate that these important scaffolding proteins that link various intracellular signaling pathways to the extracellular matrix are modified and have altered subcellular distribution in AD.