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  • Title: Heparin-binding epidermal growth factor-like growth factor is a potent neurotrophic factor for PC12 cells.
    Author: Zhou Y, Besner GE.
    Journal: Neurosignals; 2010; 18(3):141-51. PubMed ID: 20847549.
    Abstract:
    Heparin-binding epidermal growth factor EGF-like growth factor (HB-EGF) is a member of the epidermal growth factor family that is expressed in many cell types. We have previously reported the effects of HB-EGF on intestinal epithelial cells and endothelial cells after exposure to ischemia/reperfusion in vivo or anoxia/reoxygenation injury in vitro. However, the effect of HB-EGF on neuronal cells is largely unexplored. In this study, we examined the effect of HB-EGF on neurite outgrowth in pheochromocytoma (PC12) cells as well as the neuroprotective effect of HB-EGF on injured PC12 cells exposed to oxygen and glucose deprivation (OGD), which mimics ischemic conditions. We found that HB-EGF significantly promotes PC12 cell neurite outgrowth and that this effect was blocked by EGF receptor (EGFR) inhibition or mitogen-activated protein kinase (MAPK) inhibition, but not by tyrosine kinase inhibition. In the face of OGD injury, HB-EGF preserves cell viability and decreases apoptosis and LDH release in PC12 cells. HB-EGF-mediated cytoprotection was abolished by EGFR inhibition and MAPK inhibition. We conclude that HB-EGF, through its interaction with the EGF receptor, activates the MAPK signaling pathway in PC12 cells under basal or injury conditions, leading to enhanced neurite outgrowth and neuroprotection against ischemic injury.
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