Journal of Molecular Neuroscience

, Volume 29, Issue 3, pp 257–267 | Cite as

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

Involvement of PI3K and Erk signaling
  • Ayelet Di Segni
  • Keren Farin
  • Ronit Pinkas-KramarskiEmail author
Original Article


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.

Index Entries

1-methyl-4-phenylpyridinium MPP ErbB/HER family neu differentiation factor NDF neuregulin NRG signal transduction tyrosine kinase 


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Copyright information

© Humana Press Inc. 2006

Authors and Affiliations

  • Ayelet Di Segni
    • 1
  • Keren Farin
    • 1
  • Ronit Pinkas-Kramarski
    • 1
    Email author
  1. 1.Department of NeurobiochemistryTel-Aviv UniversityRamat-AvivIsrael

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