ErbB4 activation inhibits MPP+-induced cell death in PC12-ErbB4 cells - Involvement of PI3K and Erk signaling
ErbB4 activation inhibits MPP+-induced cell death in PC12-ErbB4 cells - Involvement of PI3K and Erk signaling
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DOI：
10.1385/jmn:29:3:257
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发表时间：
2006-01-01
影响因子：
3.1
通讯作者：
Pinkas-Kramarski, Ronit
中科院分区：
文献类型：
--
作者：
Di Segni, Ayelet;Farin, Keren;Pinkas-Kramarski, Ronit
研究了多肽生长因子神经调节蛋白（NRG）对1-甲基-4-苯基吡啶离子（MPP+）诱导的PC12-ErbB4细胞死亡和氧化应激的神经保护作用。MPP+处理PC12-ErbB4细胞诱导细胞死亡，NRG明显减弱细胞死亡。PI3K/PKB/Akt和Ras/MapK信号通路可能介导NRG的存活作用。NRG诱导PKB/Akt和Erk的长时间激活。此外，抑制PI3K和MEK活性可阻止nrg诱导的存活效应。过表达组成活性PI3K或H-Ras （12V）抑制MPP+介导的细胞死亡。此外，NRG还能抑制MPP+介导的活性氧（ROS）升高。NRG对ROS水平的影响被PI3K和MEK抑制剂阻断，表明这两种信号通路都可以调节MPP+诱导的毒性ROS水平。综上所述，这些结果表明，在PC12-ErbB4细胞中，nrg诱导的MPP+治疗的神经保护作用需要PI3K/PKB/Akt和Ras/MapK信号网络。
The neuroprotective effects of neuregulin (NRG), a polypeptide growth factor, on 1-methyl-4-phenylpyridinium ion (MPP+)-induced cell death and oxidative stress in PC12-ErbB4 cells were investigated. Treatment of PC12-ErbB4 cells with MPP+ induced cell death that was markedly attenuated by NRG. The PI3K/PKB/Akt and Ras/MapK signaling pathways probably mediate the survival effect of NRG. NRG induces prolonged activation of PKB/Akt and Erk. Moreover, inhibition of the PI3K and MEK activities prevented the NRG-induced survival effect. Overexpression of constitutively active PI3K or H-Ras (12V) inhibited MPP+-mediated cell death. In addition, MPP+mediated reactive oxygen species (ROS) elevation was also inhibited by NRG. The effect of NRG on ROS levels was blocked by PI3K and MEK inhibitors, indicating that both signaling pathways can regulate the toxic ROS levels induced by MPP+. Taken together, these results indicate that in PC12-ErbB4 cells, the NRG-induced neuroprotective effect from MPP+ treatment, requires PI3K/PKB/Akt and Ras/MapK signaling networks.