Inhibition of neuronal apoptosis in vitro and in vivo using TAT-Mediated protein transduction
Inhibition of neuronal apoptosis in vitro and in vivo using TAT-Mediated protein transduction
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DOI：
10.1006/mcne.2002.1165
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发表时间：
2002-09-01
影响因子：
3.5
通讯作者：
Bähr, M
中科院分区：
文献类型：
--
作者：
Dietz, GPH;Kilic, E;Bähr, M
HIV TAT 蛋白含有一个 11 个氨基酸的蛋白转导结构域，充当“特洛伊肽”：与其他大分子连接，将它们携带穿过细胞膜。在这里，我们首次证明 TAT 蛋白转导结构域与抗凋亡蛋白的融合代表了一种在体外和体内拯救神经元免于凋亡变性的可行技术。当与抗凋亡蛋白 Bcl-X-L 融合时，它介导融合蛋白被神经元摄取。一旦进入细胞，TAT-Bcl-X-L 可以稳定许多天并保持其抗凋亡功能。它在体外完全阻断低钾诱导的小脑颗粒细胞凋亡。在体内，眼内注射 TAT-Bcl-X-L 时，24% 的小鼠视网膜神经节细胞免受视神经损伤引起的逆行神经元凋亡。 TAT融合蛋白的应用将来可能会极大地促进神经系统疾病的神经保护治疗策略。
The HIV TAT protein contains an 11-amino-acid protein transduction domain which acts as a "Trojan peptide": Linked to other macromolecules, it carries them across cellular membranes. Here, we demonstrate for the first time that fusion of the TAT protein transduction domain to an antiapoptotic protein represents a feasible technique to rescue neurons from apoptotic degeneration in vitro and in vivo. When fused to the antiapoptotic protein Bcl-X-L it mediated uptake of the fusion protein into neurons. Once inside the cells, TAT-Bcl-X-L was stable for many days and maintained its antiapoptotic function. It completely blocked low-potassium-induced apoptosis of cerebellar granule cells in vitro. In vivo, 24% of mouse retinal ganglion cells were prevented from undergoing retrograde neuronal apoptosis caused by optic nerve lesion when TAT-Bcl-X-L was intraocularly injected. The application of TAT fusion proteins may in the future greatly facilitate neuroprotective therapy strategies for neurological disorders.