SAG protects human neuroblastoma SH-SY5Y cells against 1-methyl-4-phenylpyridinium ion (MPP+)-induced cytotoxicity via the downregulation of ROS generation and JNK signaling
SAG protects human neuroblastoma SH-SY5Y cells against 1-methyl-4-phenylpyridinium ion (MPP+)-induced cytotoxicity via the downregulation of ROS generation and JNK signaling
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DOI：
10.1016/j.neulet.2006.11.074
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发表时间：
2007-02-14
影响因子：
2.5
通讯作者：
Park, Hee-Sae
中科院分区：
文献类型：
--
作者：
Kim, Sun-Yee;Kim, Mi-Yeon;Park, Hee-Sae
凋亡敏感基因（SAG）是一种新的锌环指蛋白，对多种氧化还原试剂具有抗凋亡和抗氧化活性。在本研究中，我们已经确定，SAG抑制1-甲基-4-苯基吡啶离子（MPP+）诱导的神经毒性通过下调ROS的产生和c-Jun N-末端激酶1（JNK 1）的活性。瞬时和组成性过表达的SAG均能抑制MPP+诱导的SH-SY 5 Y神经母细胞瘤细胞的神经毒性。在SAG表达细胞中，与仅用MPP+处理的细胞相比，MPP+诱导的ROS产生被抑制至显著程度。MPP+诱导的JNK 1活化也被SAG显著抑制。此外，SAG抑制SH-SY 5 Y细胞中MEKK 1依赖的c-Jun转录活性。因此，我们得出结论，SAG是一种细胞保护性分子，它似乎是一种抗氧化剂，抑制MPP+诱导的神经毒性。(c)2006爱思唯尔爱尔兰有限公司保留所有权利。
Sensitive to anoptosis gene (SAG), a novel zinc RING finger protein, exhibits anti-apoptotic and antioxidant activity against a variety of redox reagents. In the present study, we have determined that SAG suppresses 1-methyl-4-phenylpyridinium ion (MPP+)-induced neurotoxicity via the downregulation of ROS generation and c-Jun N-terminal kinase 1 (JNK1) activity. Both transient and constitutively overexpressed SAG were found to inhibit the MPP+-induced neurotoxicity of SH-SY5Y neuroblastoma cells. In the SAG-expressing cells, MPP+ induced ROS generation was suppressed to a significant degree as compared to the cells treated only with MPP+. MPP+-induced JNK1 activation was also determined to be suppressed markedly by SAG. Furthermore, SAG inhibits MEKK1 dependent c-Jun transcription activity in SH-SY5Y cells. Thus, we concluded that SAG is a cellular protective molecule, which appears to function as an antioxidant, suppressing MPP+-induced neurotoxicity. (c) 2006 Elsevier Ireland Ltd. All rights reserved.