TAT-mediated delivery of Bcl-xL protein is neuroprotective against neonatal hypoxic-ischemic brain injury via inhibition of caspases and AIF.

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作者：

Y Wei，G Cao，MJ Johnnides，AP Signore，Y Luo，RW Hickey，J Chen

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摘要：

Systemic delivery of recombinant Bcl-xL fusion protein containing the TAT protein transduction domain attenuated neonatal brain damage following hypoxic ischemia (H–I). Within 30 min after intraperitoneal injection of TAT–Bcl-xL protein into 7-day-old rats, substantially enhanced levels of Bcl-xL were found in several brain regions. Administration of TAT–Bcl-xL at the conclusion of the H–I insult decreased cerebral tissue loss in a dose-dependent manner measured 1 and 8 weeks later. Neuroprotection provided by TAT–Bcl-xL was significantly greater than that of the pan-caspase inhibitor BAF, suggesting that protection is only partially attributable to caspase inhibition by TAT–Bcl-xL. TAT–Bcl-xL not only inhibited caspases-3 and -9 activities after H–I but also prevented nuclear translocation of AIF. Taken together, these results substantiate the feasibility of peripheral delivery of an anti-apoptotic factor into the brain of neonatal animals to reduce H–I-induced brain injury.

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关键词：

Protein transduction Hypoxia Ischemia Apoptosis Cerebral

DOI：

10.1016/j.nbd.2005.07.015

被引量：

265

年份：

2006