The neuroprotective role of TERT via an antiapoptotic mechanism in neonatal rats after hypoxia–ischemia brain injury
The neuroprotective role of TERT via an antiapoptotic mechanism in neonatal rats after hypoxia–ischemia brain injury
复制标题
DOI：
10.1016/j.neulet.2012.03.014
复制
发表时间：
2012-04
影响因子：
2.5
通讯作者：
F. Zhao;Y. Qu;T. Xiong;Zhoujin Duan;Qianghua Ye;D. Mu
中科院分区：
文献类型：
--
作者：
F. Zhao;Y. Qu;T. Xiong;Zhoujin Duan;Qianghua Ye;D. Mu
端粒酶逆转录酶(TERT)可以调节细胞的凋亡和增殖。已有研究表明，在成人脑缺血模型中可以诱导TERT的表达。在本研究中，我们研究了TERT在新生大鼠缺氧缺血模型缺血性神经元死亡中的作用。用出生后第10天的SD大鼠建立缺氧缺血(HI)模型和单纯缺氧(H)模型。幼崽在受侮辱后4、8、12、24或48小时被杀。分别于伤后即刻将含有模拟、TERT反义或正义片段与Fugene HD混合的质粒注入右侧脑室。24小时后继续注射。给药后24小时处死幼鼠。Western印迹法检测TERT和半胱氨酸天冬氨酸氨基转移酶-3(CC3)的表达。用末端脱氧核苷酸转移酶介导的dUTP缺口末端标记(TUNEL)法检测细胞凋亡。我们发现H/HI处理诱导了神经细胞的凋亡以及TERT和CC3的表达。但H组TERT明显高于HI组，而CC3和细胞凋亡率则相反，反义TERT表达明显减弱HI诱导的TERT表达，上调CC3表达，增加细胞凋亡率。我们的结果表明，TERT可能通过抑制caspase-3的激活而发挥抗凋亡蛋白的作用，但其潜在机制尚需进一步研究。
Telomerase reverse transcriptase (TERT) can regulate cell apoptosis and proliferation. It has been shown that TERT expression can be induced in models of adult brain ischemia. In the present study, we investigated the role of TERT in ischemic neuronal death in neonatal hypoxic–ischemic rats model. Postnatal day 10 Sprague-Dawley rats were used to establish hypoxia–ischemia (HI) model and hypoxia alone (H) model. Pups were killed at 4, 8, 12, 24, or 48h after the insult. Plasmid containing mock, TERT antisense or sense fragment mixed with Fugene HD was injected to the right lateral ventricle immediately after the insult respectively. Additional injection was performed after 24h. Pups were sacrificed 24h after the administration. TERT and cleaved caspase-3 (CC3) expression were measured by Western blot. Apoptotic cells were detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) staining. We found that H/HI treatment induced neuronal apoptosis and expression of TERT and CC3. However, TERT was higher in H than in HI pups whereas CC3 and apoptosis were opposite, TERT antisense plasmid markedly attenuated TERT expression induced by HI, upregualted CC3 expression, and increased apoptosis. Our results indicate that TERT might function as an anti-apoptotic protein by inhibiting activation of caspase-3, while further studies are needed to evaluate underlying mechanisms.