Send to:

Choose Destination
See comment in PubMed Commons below
Free Radic Res. 2010 Jun;44(6):645-54. doi: 10.3109/10715761003692537.

Induction of neurite outgrowth by alpha-phenyl-N-tert-butylnitrone through nitric oxide release and Ras-ERK pathway in PC12 cells.

Author information

  • 1Laboratory of Radiation Biology, Department of Environmental Veterinary Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Kita-Ku, Sapporo, Hokkaido, Japan.


It has previously been suggested that the spin trap agent alpha-phenyl-N-tert-butylnitrone (PBN) induces neurite outgrowth through activation of the Ras-ERK pathway in PC12 cells. However, the chemical properties of PBN contributing to its biological function and the detailed mechanism for the activation of Ras by PBN remain unknown. This study demonstrates that the hydrophobic structure of PBN is related to the activation of Ras, by comparing with hydrophilic analogues of PBN. [(14)C]-labelled PBN was found to localize in the lipid fraction and activate Ras indirectly. On the other hand, neurite outgrowth by PBN was inhibited by a nitric oxide (NO) scavenger. Moreover, the neurite outgrowth induced by PBN and the NO donor NOR4 was inhibited by the dominant negative Ras or MAPK/ERK inhibitor. Taken together, these results suggest that PBN is incorporated into the plasma membrane and induces neurite outgrowth in PC12 cells by activating the Ras-ERK pathway through NO release.

[PubMed - indexed for MEDLINE]
PubMed Commons home

PubMed Commons

How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Taylor & Francis
    Loading ...
    Write to the Help Desk