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

Autor: Wei Yin, Guodong Cao, Michael J. Johnnides, Armando P. Signore, Yumin Luo, Robert W. Hickey, Jun Chen
Jazyk: angličtina
Rok vydání: 2006
Předmět:
Zdroj: Neurobiology of Disease, Vol 21, Iss 2, Pp 358-371 (2006)
Druh dokumentu: article
ISSN: 1095-953X
DOI: 10.1016/j.nbd.2005.07.015
Popis: 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.
Databáze: Directory of Open Access Journals