ErbB4 activation inhibits MPP+-induced cell death in PC12-ErbB4 cells
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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 Entries1-methyl-4-phenylpyridinium MPP ErbB/HER family neu differentiation factor NDF neuregulin NRG signal transduction tyrosine kinase
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- Marchionni M. A., Cannella B., Hoban C., et al. (1999) Neuregulin in neuron/glial interactions in the central nervous system. GGF2 diminishes autoimmune demyelination promotes oligodendrocyte progenitor expansion, and enhances remyelination. Adv. Exp. Med. Biol. 468, 283–295.CrossRefPubMedGoogle Scholar
- Rieff H. I., Raetzman L. T., Sapp D. W., Yeh H. H., Siegel R. E., and Corfas G. (1999) Neuregulin induces GABA(A) receptor subunit expression and neurite outgrowth in cerebellar granule cells. J. Neurosci. 19, 10,757–10,766.Google Scholar
- Shimoke K. and Chiba H. (2001) Nerve growth factor prevents 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced cell death via the Akt pathway by suppressing caspace-3-like activity using PC12 cells, relevance to therapeutical application for Parkinson's disease. J. Neurosci. Res. 63, 402–409.CrossRefPubMedGoogle Scholar
- Sonoda Y., Watanabe S., Matsumoto Y., Aizu-Yokota E., and Kasahara T. (1999) FAK is the upstream signal protein of the phosphatidylinositol 3-kinase-Akt survival pathway in hydrogen peroxide-induced apoptosis of a human glioblastoma cell line. J. Biol. Chem. 274, 10,566–10,570.CrossRefGoogle Scholar
- Tatton N. A. and Kish S. J. (1997) In situ detection of apoptotic nuclei in the substantia nigra compacta of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated mice using terminal deoxynucleotidyl transferase labelling and acridine orange staining. Neuroscience 77, 1037–1048.CrossRefPubMedGoogle Scholar