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ErbB4 activation inhibits MPP+-induced cell death in PC12-ErbB4 cells

Involvement of PI3K and Erk signaling

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Abstract

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. Over-expression 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.

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Authors and Affiliations

  1. Department of Neurobiochemistry, Tel-Aviv University, Ramat-Aviv, Israel

    Ayelet Di Segni, Keren Farin & Ronit Pinkas-Kramarski

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  1. Ayelet Di Segni
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  2. Keren Farin
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  3. Ronit Pinkas-Kramarski
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Correspondence to Ronit Pinkas-Kramarski.

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These authors contributed equally to this work.

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Di Segni, A., Farin, K. & Pinkas-Kramarski, R. ErbB4 activation inhibits MPP+-induced cell death in PC12-ErbB4 cells. J Mol Neurosci 29, 257–267 (2006). https://doi.org/10.1385/JMN:29:3:257

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