您当前所在位置: 首页 > 学者

葛海良

  • 9浏览

  • 0点赞

  • 0收藏

  • 0分享

  • 64下载

  • 0评论

  • 引用

期刊论文

In Vivo Delivery of a Bcl-xL Fusion Protein Containing the TAT Protein Transduction Domain Protects against Ischemic Brain Injury and Neuronal Apoptosis

葛海良Guodong Cao Wei Pei Hailiang Ge Qinhua Liang Yumin Luo Frank R. Sharp Aigang Lu Ruiqiong Ran Steven H. Graham and Jun Chen

J. Neurosci., July 1, 2002, 22 (13): 5423-5431,-0001,():

URL:

摘要/描述

Bcl-xL is a well characterized death-suppressing molecule of the Bcl-2 family. Bcl-xL is expressed in embryonic and adult neurons of the CNS and may play a critical role in preventing neuronal apoptosis that occurs during brain development or results from diverse pathologic stimuli, including cerebral ischemia. In this study, we used a novel approach to study the potential neuroprotective effect of Bcl-xL as a therapeutic agent in the murine model of focal ischemia/reperfusion. We created a Bcl-xL fusion protein, designated as PTD-HA-Bcl-xL, which contains the protein transduction domain (PTD) derived from the human immunodeficiency TAT protein. We demonstrated that this fusion protein is highly efficient in transducing into primary neurons in cultures and potently inhibited staurosporininduced neuronal apoptosis. Furthermore, intraperitoneal injection of PTD-HA-Bcl-xL into mice resulted in robust protein transduction in neurons in various brain regions within 1-2 hr, and decreased cerebral infarction (up to 40%) in a dosedependent manner, as determined at 3 d after 90 min of focal ischemia. PTD-HA-Bcl-xL was effective even when it was administered after the completion of ischemia (up to 45 min), and the protective effect was independent of the changes in cerebral blood flow or other physiological parameters. Finally, as shown by immunohistochemistry, Western blotting, and substrate-cleavage assays, PTD-HA-Bcl-xL attenuated ischemiainduced caspase-3 activation in ischemic neurons. These results thus confirm the neuroprotective effect of Bcl-xL against ischemic brain injury and provide the first evidence that the PTD can be used to efficiently transduce a biologically active neuroprotectant in experimental cerebral ischemia.

【免责声明】以下全部内容由[葛海良]上传于[2011年04月21日 09时53分46秒],版权归原创者所有。本文仅代表作者本人观点,与本网站无关。本网站对文中陈述、观点判断保持中立,不对所包含内容的准确性、可靠性或完整性提供任何明示或暗示的保证。请读者仅作参考,并请自行承担全部责任。

我要评论

全部评论 0

本学者其他成果

    同领域成果