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

Authors
  • Yin, Wei
  • Cao, Guodong
  • Johnnides, Michael J
  • Signore, Armando P
  • Luo, Yumin
  • Hickey, Robert W
  • Chen, Jun
Type
Published Article
Journal
Neurobiology of disease
Publication Date
Feb 01, 2006
Volume
21
Issue
2
Pages
358–371
Identifiers
PMID: 16140540
Source
Medline
License
Unknown

Abstract

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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