Tat-antioxidant 1 protects against stress-induced hippocampal HT-22 cells death and attenuate ischaemic insult in animal model.
Tat-antioxidant 1 protects against stress-induced hippocampal HT-22 cells death and attenuate ischaemic insult in animal model.
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DOI：
10.1111/jcmm.12513
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发表时间：
2015-06
影响因子：
5.3
通讯作者：
Choi SY
中科院分区：
文献类型：
--
作者：
Kim SM;Hwang IK;Yoo DY;Eum WS;Kim DW;Shin MJ;Ahn EH;Jo HS;Ryu EJ;Yong JI;Cho SW;Kwon OS;Lee KW;Cho YS;Han KH;Park J;Choi SY
氧化应激诱导的活性氧（ROS）与多种神经元疾病有关。抗氧化剂1 （Atox1）调节铜稳态，促进细胞抗氧化防御由ROS产生的毒素。然而，Atox1蛋白在缺血中的作用尚不清楚。在这项研究中，我们生成了一个融合了Tat-Atox1的蛋白转导结构域，并研究了Tat-Atox1在氧化应激诱导的海马HT-22细胞死亡和缺血损伤动物模型中的作用。Tat-Atox1有效地转导到HT-22细胞中，并保护细胞免受过氧化氢（H2O2）诱导的毒性影响，包括ROS水平的增加和DNA断裂。同时，Tat-Atox1调节细胞存活信号，如p53、Bad/Bcl-2、Akt和丝裂原活化蛋白激酶（MAPKs）。在动物缺血模型中，转导的Tat-Atox1保护海马CA1区域的神经元细胞死亡。此外，Tat-Atox1显著降低缺血性损伤后星形胶质细胞和小胶质细胞的活化以及CA1区域的脂质过氧化。综上所述，这些结果表明，在动物缺血模型中，转导的Tat-Atox1可保护氧化应激诱导的HT-22细胞死亡和神经元损伤。因此，我们认为Tat-Atox1有潜力作为治疗氧化应激诱导的缺血损伤的治疗剂。
Oxidative stress-induced reactive oxygen species (ROS) are responsible for various neuronal diseases. Antioxidant 1 (Atox1) regulates copper homoeostasis and promotes cellular antioxidant defence against toxins generated by ROS. The roles of Atox1 protein in ischaemia, however, remain unclear. In this study, we generated a protein transduction domain fused Tat-Atox1 and examined the roles of Tat-Atox1 in oxidative stress-induced hippocampal HT-22 cell death and an ischaemic injury animal model. Tat-Atox1 effectively transduced into HT-22 cells and it protected cells against the effects of hydrogen peroxide (H2O2)-induced toxicity including increasing of ROS levels and DNA fragmentation. At the same time, Tat-Atox1 regulated cellular survival signalling such as p53, Bad/Bcl-2, Akt and mitogen-activate protein kinases (MAPKs). In the animal ischaemia model, transduced Tat-Atox1 protected against neuronal cell death in the hippocampal CA1 region. In addition, Tat-Atox1 significantly decreased the activation of astrocytes and microglia as well as lipid peroxidation in the CA1 region after ischaemic insult. Taken together, these results indicate that transduced Tat-Atox1 protects against oxidative stress-induced HT-22 cell death and against neuronal damage in animal ischaemia model. Therefore, we suggest that Tat-Atox1 has potential as a therapeutic agent for the treatment of oxidative stress-induced ischaemic damage.
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影响因子：
4.8
作者：
Itoh, Shinichi;Kim, Ha Won;Fukai, Tohru
通讯作者：
Fukai, Tohru
影响因子：
8.3
作者：
Ito, D;Tanaka, K;Fukuuchi, Y
通讯作者：
Fukuuchi, Y
影响因子：
3.8
作者：
Kim, Dae Won;Lee, Sung Ho;Choi, Soo Young
通讯作者：
Choi, Soo Young
影响因子：
7.4
作者：
Kim, Young Nam;Jung, Hyo Young;Choi, Soo Young
通讯作者：
Choi, Soo Young
影响因子：
2
作者：
Ferrer, I;López, E;Martí, E
通讯作者：
Martí, E