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

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作者：

G Cao，P Wei，H Ge，Q Liang，Y Luo，FR Sharp，A Lu，R Ran，SH Graham，J Chen

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摘要：

Bcl-xL is a well characterized -suppressing molecule of the family. Bcl-xL is expressed in and adult neurons of the and may play a critical role in preventing neuronal that occurs during or results from diverse pathologic stimuli, including . In this study, we used a novel approach to study the potential neuroprotective effect of Bcl-xL as a therapeutic agent in the model of focal /reperfusion. We created a Bcl-xL fusion protein, designated as -HA-Bcl-xL, which contains the protein domain () derived from the protein. We demonstrated that this fusion protein is highly efficient in transducing into primary neurons in cultures and potently inhibited -induced neuronal . Furthermore, intraperitoneal injection of -HA-Bcl-xL into resulted in robust protein in neurons in various brain regions within 1-2 hr, and decreased (up to approximately 40%) in a dose-dependent manner, as determined at 3 d after 90 min of focal . -HA-Bcl-xL was effective even when it was administered after the completion of (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, -HA-Bcl-xL attenuated -induced 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 can be used to efficiently transduce a biologically active neuroprotectant in experimental .

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关键词：

Chromatophore Bacteriochlorophyll-protein complex Cytochrome Reaction center B -875 light-harvesting bacteriochlorophyll complexes absorbing maximally near 875 B -850 850 nm, respectively P -605 reaction center absorption band which upon oxidation, exhibits a maximal absorbance decrease near 605 nm